Humans could face a reproductive crisis if action is not taken to tackle a drop in sperm count, researchers have warned after finding the rate of decline is accelerating.
A study published in the journal Human Reproduction Update, based on 153 estimates from men who were probably unaware of their fertility, suggests that the average sperm concentration fell from an estimated 101.2m per ml to 49.0m per ml between 1973 and 2018 – a drop of 51.6%. Total sperm counts fell by 62.3% during the same period.
Research by the same team, reported in 2017, found that sperm concentration had more than halved in the last 40 years. However, at the time a lack of data for other parts of the world meant the findings were focused on a region encompassing Europe, North America and Australia. The latest study includes more recent data from 53 countries.
Declines in sperm concentration were seen not only in the region previously studied, but in Central and South America, Africa and Asia.
Moreover, the rate of decline appears to be increasing: looking at data collected in all continents since 1972, the researchers found sperm concentrations declined by 1.16% per year. However, when they looked only at data collected since the year 2000, the decline was 2.64% per year.
“I think this is another signal that something is wrong with the globe and that we need to do something about it. So yes, I think it’s a crisis, that we [had] better tackle now, before it may reach a tipping point which may not be reversible,” said Prof Hagai Levine, first author of the research from the Hebrew University of Jerusalem.
Previous studies have suggested that fertility is compromised if sperm concentration falls below about 40m per ml. While the latest estimate is above this threshold, Levine noted that this is a mean figure, suggesting the percentage of men below this threshold will have increased.
“Such a decline clearly represents a decline in the capacity of the population to reproduce,” he said.
While the study accounted for factors including age and how long men had gone without ejaculation, and excluded men known to suffer from infertility, it has limitations, including that it did not look at other markers of sperm quality.
Allan Pacey, professor of andrology at the University of Sheffield, who was not involved in the work, praised the analysis, but said he remained on the fence over whether there is a decline.
“Counting sperm, even with the gold standard technique of [the laboratory process] haemocytometry, is really difficult,” he said. “I believe that over time we have simply got better at it because of the development of training and quality control programmes around the world. I still think this is much of what we are seeing in the data.”
However, Levine dismissed such concerns, adding that, in any case, the decline has been more pronounced in more recent years.
While it is unclear what might be behind the apparent trend, one hypothesis is that endocrine-disrupting chemicals or other environmental factors may play a role, acting on the foetus in the womb. Experts say factors such as smoking, drinking, obesity and poor diet might also play a role, and that a healthy lifestyle may help to boost sperm counts.
Tina Kold Jensen of the University of Southern Denmark said the new study recapitulated a concerning trend. “You keep on finding the same trend, no matter how many studies you include – that is a bit scary to me,” she said.
Prof Richard Sharpe, an expert in male reproductive health at the University of Edinburgh, said the new data showed that the trend appeared to be a worldwide phenomenon.
Sharpe said the decline could mean it takes longer for couples to conceive and, for many, time is not on their side as they are delaying trying to conceive until the woman is in her 30s or 40s, when her fertility is already reduced.
“The key point that needs to be made is that this is desperately bad news for couple fertility,” he said.
But, said Sharpe, “These issues are not just a problem for couples trying to have kids. They are also a huge problem for society in the next 50-odd years as less and less young people will be around to work and support the increasing bulge of elderly folk.”
Studies in mammals have shown that the ‘memories’ of various environmental effects – such as diet, weight, and stress – can be passed on from fathers to offspring, despite these effects not being coded for in the DNA sequences carried by sperm.
Thanks to a 2021 study, we have an explanation for how it’s possible.
The story has much to do with epigenetics. Molecules that attach themselves to DNA can act like on-off switches that control which sections of DNA get used – but until 2021, we didn’t know which of these molecules can carry the settings marked by a father’s life experiences, to be incorporated into an embryo via sperm.
“The big breakthrough with this study is that it has identified a non-DNA-based means by which sperm remember a father’s environment (diet) and transmit that information to the embryo,” McGill University epigeneticist Sarah Kimmins said in 2021.
Using mice, epigeneticist Ariane Lismer and colleagues were able to demonstrate that the effects of a folate-deficient diet could be passed on by altering histone molecules in sperm. Simply put, histones are really basic proteins that DNA winds around for tangle-free storage.
In mammals, when male bodies build sperm, they throw out most of the histone spools, to allow for tighter packing.
But a small percentage still remains (1 percent in mice and 15 percent in humans), providing scaffolding for DNA in regions specific to sperm creation and function, metabolism, and embryo development – to allow the cellular mechanisms to make use of these DNA instructions.
Chemical modification of these histones – the most common form being methylation – is what allows or prevents the DNA to be ‘read’ so that it can be transcribed into protein products. Poor diet can cause these histones to change their methylation status.
This is why we hear about the importance of folate for women during pregnancy: A mother’s folate helps stabilize DNA methylation in their young.
By feeding male mice a folate-deficient diet from the time they were weaned, the researchers were able to track the changes to histones from the male’s sperm and in the resulting embryos. And indeed, sperm histone changes were also present in the developing embryo.
“No one has been able to track how those heritable environmental signatures are transmitted from the sperm to the embryo before,” said Lismer in 2021.
The team also discovered these effects could be cumulative and lead to an increase in the severity of birth defects.
Interestingly, the birth defects seen in the mice, including underdevelopment at birth and spinal abnormalities, are well documented in folate-deficient human populations.
The researchers hope that expanding our knowledge of inheritance mechanisms will reveal additional ways to treat and prevent such conditions. But there is a lot more to work out before then.
“Our next steps will be to determine if these harmful changes induced in the sperm proteins (histones) can be repaired. We have exciting new work that suggests that this is indeed the case,” said Kimmins.
This research was published in Developmental Cell.
A version of the article was first published in March 2021.
In vitro fertilization (IVF) using frozen embryos may be associated with a 74% higher risk of hypertensive disorders in pregnancy, according to new research published today in Hypertension, an American Heart Association journal. In comparison, the study found that pregnancies from fresh embryo transfers – transferring the fertilized egg immediately after in vitro fertilization (IVF) instead of a frozen, fertilized egg – and pregnancy from natural conception shared a similar risk of developing a hypertensive disorder.
High blood pressure during pregnancy often signals preeclampsia, a pregnancy complication including persistent high blood pressure that can endanger the health and life of the mother and fetus. Approximately 1 out of every 25 pregnancies in the United States results in preeclampsia, according to the American Heart Association.
One IVF treatment process available utilizes frozen embryos: after an egg is fertilized by sperm in the lab, it is frozen using a cryopreservation process before being thawed and transferred to the uterus at a later date. The procedure is becoming more common because of the significantly improved freezing technology or cryopreservation methods that started in the late 2000s and because more patients are choosing to freeze embryos, according to the study authors. Yet, frozen embryo transfer is known to be associated with a higher risk of hypertensive disorders in pregnancy than both natural conception and fresh embryo transfer. However, prior to this study, it was unknown whether this was due to the freezing process or a risk factor from the parents.
Frozen embryo transfers are now increasingly common all over the world, and in the last few years, some doctors have begun skipping fresh embryo transfer to routinely freeze all embryos in their clinical practice, the so-called ‘freeze-all’ approach.”
Sindre H. Petersen, M.D., Study’s Lead Author and Ph.D. Fellow, Norwegian University of Science and Technology in Trondheim, Norway
Researchers examined national data from medical birth registries from Denmark, Norway and Sweden of nearly 2.4 million women who were ages 20 to 44 years old who had single deliveries and gave birth during the study period – from 1988 through 2015. These data were the basis of a population-based study that also included a comparison of women who had both an IVF pregnancy and a naturally conceived pregnancy, called sibling comparison. This approach was used to isolate if the potential reason for the hypertensive disorders was attributable to parental factors or to the IVF treatment.
The study included more than 4.5 million pregnancies, of which 4.4 million were naturally conceived; more than 78,000 pregnancies were fresh embryo transfers; and more than 18,000 pregnancies were frozen embryo transfers. Among all of the pregnancies, more than 33,000 were grouped for sibling comparison – mothers who conceived via more than one of these methods. The study is the largest to-date using sibling comparison. The odds of developing hypertensive disorders in pregnancy after fresh vs. frozen embryo transfers compared to natural conception were adjusted for variables such as birth year and the mother’s age.
“In summary, although most IVF pregnancies are healthy and uncomplicated,” Petersen said. “This analysis found that the risk of high blood pressure in pregnancy was substantially higher after frozen embryo transfer compared to pregnancies from fresh embryo transfer or natural conception.”
Specifically, the study found:
In the population analysis, women whose pregnancy was the result of a frozen embryo transfer were 74% more likely to develop hypertensive disorders in pregnancy compared to those who conceived naturally.
Among women who had both a natural conception and an frozen embryo transfer IVF conception (the sibling comparison), the risk of hypertensive disorders in pregnancy after frozen embryo transfer was twice as high compared to pregnancies from natural conception.
Pregnancies from fresh embryo transfer did not have a higher risk of developing hypertensive disorders compared to natural conception, neither in population level analysis nor in sibling comparisons.
“Our sibling comparisons indicate that the higher risk is not caused by factors related to the parents, rather, however, that some IVF treatment factors may be involved,” Petersen said. “Future research should investigate which parts of the frozen embryo transfer process may impact risk of hypertension during pregnancy.”
Among other findings, women in the study who gave birth after IVF pregnancies were average age 34 years for frozen embryo transfer, 33 years for fresh embryo transfer and 29 years for those who conceived naturally. About 7% of babies conceived from frozen embryo transfer were born preterm (before 40 weeks gestation) and 8% of babies after fresh embryo transfer were born preterm, compared to 5% of babies after natural conception.
In addition to preeclampsia, the researchers defined hypertensive disorders in pregnancy as a combined outcome, including gestational hypertension, eclampsia (the onset of seizures in those with preeclampsia) and chronic hypertension with superimposed preeclampsia.
One limitation of the study was the lack of data on the kind of frozen embryo cycle, so they were not able to pinpoint what part of the frozen cycle or frozen transfer may contribute to the higher risk of hypertensive disorders. Another limitation is that data from Scandinavian countries may limit generalizing the findings to people in other countries.
“Our results highlight that careful consideration of all benefits and potential risks is needed before freezing all embryos as a routine in clinical practice. A comprehensive, individualized conversation between physicians and patients about the benefits and risks of a fresh vs. frozen embryo transfer is key,” said Petersen.
Source:
American Heart Association
Journal reference:
Petersen, S.H., et al. (2022) Risk of Hypertensive Disorders in Pregnancy After Fresh and Frozen Embryo Transfer in Assisted Reproduction: A Population-Based Cohort Study With Within-Sibship Analysis. Hypertension. doi.org/10.1161/HYPERTENSIONAHA.122.19689.
Stem cells are unspecialized cells that can be manipulated into becoming mature cells with special functions.
“Our mouse embryo model not only develops a brain, but also a beating heart, all the components that go on to make up the body,” said lead study author Magdalena Zernicka-Goetz, professor of mammalian development and stem cell biology at the University of Cambridge in the United Kingdom.
“It’s just unbelievable that we’ve got this far. This has been the dream of our community for years, and a major focus of our work for a decade, and finally we’ve done it.”
The paper is an exciting advance and tackles a challenge scientists face studying mammal embryos in utero, said Marianne Bronner, a professor of biology at the California Institute of Technology in Pasadena (Caltech). Bronner was not involved in the study.
“These develop outside of the mother and therefore can be easily visualized through critical developmental stages that were previously difficult to access,” Bronner added.
The researchers hope to move from mouse embryos to creating models of natural human pregnancies — many of which fail in the early stages, Zernicka-Goetz said.
By watching the embryos in a lab instead of a uterus, scientists got a better view into the process to learn why some pregnancies might fail and how to prevent it, she added.
For now, researchers have only been able to track about eight days of development in the mouse synthetic embryos, but the process is improving, and they are already learning a lot, said study author Gianluca Amadei, a postdoctoral researcher at the University of Cambridge.
“It reveals the fundamental requirements that have to be fulfilled to make the right structure of the embryo with its organs,” Zernicka-Goetz said.
Where it stands, the research doesn’t apply to humans and “there needs to be a high degree of improvement for this to be truly useful,” said Benoit Bruneau, the director of the Gladstone Institute of Cardiovascular Disease and a senior investigator at Gladstone Institutes. Bruneau was not involved in the study.
But researchers see important uses for the future. The process can be used immediately to test new drugs, Zernicka-Goetz said. But in the longer term, as scientists move from mouse synthetic embryos to a human embryo model, it also could help build synthetic organs for people who need transplants, Zernicka-Goetz added.
“I see this work as being the first example of work of this kind,” said study author David Glover, research professor of biology and biological engineering at Caltech.
How they did it
In utero, an embryo needs three types of stem cells to form: One becomes the body tissue, another the sac where the embryo develops, and the third the placenta connecting parent and fetus, according to the study.
In Zernicka-Goetz’s lab, researchers isolated the three types of stem cells from embryos and cultured them in a container angled to bring the cells together and encourage crosstalk between them.
Day by day, they were able to see the group of cells form into a more and more complex structure, she said.
There are ethical and legal considerations to address before moving to human synthetic embryos, Zernicka-Goetz said. And with the difference in complexity between mouse and human embryos, it could be decades before researchers are able to do a similar process for human models, Bronner said.
But in the meantime, the information learned from the mouse models could help “correct failing tissues and organs,” Zernicka-Goetz said.
The mystery of human life
The early weeks after fertilization are made up of these three different stem cells communicating with one another chemically and mechanically so the embryo can grow properly, the study said.
“So many pregnancies fail around this time, before most women (realize) they are pregnant,” said Zernicka-Goetz, who is also professor of biology and biological engineering at Caltech. “This period is the foundation for everything else that follows in pregnancy. If it goes wrong, the pregnancy will fail.”
But by this stage, an embryo created through in vitro fertilization is already implanted in the parent, so scientists have limited visibility into the processes it is going through, Zernicka-Goetz said.
They were able to develop foundations of a brain — a first for models such as these and a “holy grail for the field,” Glover said.
“This period of human life is so mysterious, so to be able to see how it happens in a dish — to have access to these individual stem cells, to understand why so many pregnancies fail and how we might be able to prevent that from happening — is quite special,” Zernicka-Goetz said in a press release. “We looked at the dialogue that has to happen between the different types of stem cell at that time — we’ve shown how it occurs and how it can go wrong.”
Natural and synthetic embryos side by side show comparable brain and heart formation. Credit: Amadei and Handford
Scientists from the University of Cambridge have created model embryos from mouse stem cells that form a brain, a beating heart, and the foundations of all the other organs of the body. It represents a new avenue for recreating the first stages of life.
The team of researchers, led by Professor Magdalena Zernicka-Goetz, developed the embryo model without eggs or sperm. Instead, they used stem cells – the body’s master cells, which can develop into almost any cell type in the body.
“It’s just unbelievable that we’ve got this far. This has been the dream of our community for years, and major focus of our work for a decade and finally we’ve done it.” — Magdalena Zernicka-Goetz
By guiding the three types of stem cells found in early mammalian development to the point where they start interacting, the researchers mimicked natural processes in the lab. The scientists were able to get the stem cells to ‘talk’ to each other by inducing the expression of a particular set of genes and establishing a unique environment for their interactions.
The stem cells self-organized into structures that progressed through the successive developmental stages until they had beating hearts and the foundations of the brain They also had the yolk sac where the embryo develops and gets nutrients from in its first weeks. Unlike other synthetic embryos, the Cambridge-developed models reached the point where the entire brain, including the anterior portion, began to develop. This is a further point in development than has been achieved in any other stem cell-derived model.
According to the team, their results could help researchers understand why some embryos fail while others go on to develop into a healthy pregnancy. In addition, the results could be used to guide the repair and development of synthetic human organs for transplantation. The study, which is the result of more than a decade of research that progressively led to more and more complex embryo-like structures, was reported on August 25, 2022, in the journal Nature.
Natural and synthetic embryos side by side show comparable brain and heart formation. Credit: Amadei and Handford
“Our mouse embryo model not only develops a brain, but also a beating heart, all the components that go on to make up the body,” said Zernicka-Goetz, Professor in Mammalian Development and Stem Cell Biology in Cambridge’s Department of Physiology, Development and Neuroscience. “It’s just unbelievable that we’ve got this far. This has been the dream of our community for years, and major focus of our work for a decade and finally we’ve done it.”
A “dialog” between the tissues that will form the embryo and the tissues that will connect the embryo to the mother is necessary for the healthy development of a human embryo. Three different stem cell types begin to form in the first week following fertilization; one of these will eventually develop into the bodily tissues, while the other two support the embryo’s development. One of these extraembryonic stem cell types will become the placenta, which connects the fetus to the mother and provides oxygen and nutrients. The second is the yolk sac, where the embryo grows and where it gets its nutrients from in early development.
Many pregnancies fail at the point when the three types of stem cells begin to send mechanical and chemical signals to each other, which instruct the embryo on how to develop properly.
“So many pregnancies fail around this time, before most women realize they are pregnant,” said Zernicka-Goetz, who is also Professor of Biology and Biological Engineering at Caltech. “This period is the foundation for everything else that follows in pregnancy. If it goes wrong, the pregnancy will fail.”
Professor Zernicka-Goetz in the lab. Credit: University of Cambridge
Professor Zernicka-Goetz’s group in Cambridge has been studying these earliest stages of pregnancy over the past decade, in order to understand why some pregnancies fail and some succeed.
“The stem cell embryo model is important because it gives us accessibility to the developing structure at a stage that is normally hidden from us due to the implantation of the tiny embryo into the mother’s womb,” said Zernicka-Goetz. “This accessibility allows us to manipulate genes to understand their developmental roles in a model experimental system.”
To guide the development of their synthetic embryo, the scientists put together cultured stem cells representing each of the three types of tissue in the right proportions and environment to promote their growth and communication with each other, eventually self-assembling into an embryo.
The research team discovered that the extraembryonic cells signal to embryonic cells by chemical signals but also mechanistically, or through touch, guiding the embryo’s development.
“This period of human life is so mysterious, so to be able to see how it happens in a dish – to have access to these individual stem cells, to understand why so many pregnancies fail and how we might be able to prevent that from happening – is quite special,” said Zernicka-Goetz. “We looked at the dialogue that has to happen between the different types of stem cell at that time – we’ve shown how it occurs and how it can go wrong.”
A major advance in the study is the ability to generate the entire brain, in particular the anterior part, which has been a major goal in the development of synthetic embryos. This works in Zernicka-Goetz’s system because this part of the brain requires signals from one of the extraembryonic tissues to be able to develop. The team thought that this might be taking place from their 2018 and 2021 studies, which used the same component cells to develop into embryos at a slightly earlier stage. Now, by pushing development just one day further, they can definitively say that their model is the very first to signal development of the anterior, and in fact the whole, brain.
“This opens new possibilities to study the mechanisms of neurodevelopment in an experimental model,” said Zernicka-Goetz. “In fact, we demonstrate the proof of this principle in the paper by knocking out a gene already known to be essential for formation of the neural tube, precursor of the nervous system, and for brain and eye development. In the absence of this gene, the synthetic embryos show exactly the known defects in brain development as in an animal carrying this mutation. This means we can begin to apply this kind of approach to the many genes with unknown function in brain development.”
While the current research was carried out in mouse models, the researchers are developing similar human models with the potential to be directed towards the generation of specific organ types to understand mechanisms behind crucial processes that would be otherwise impossible to study in real embryos. At present, UK law permits human embryos to be studied in the laboratory only up to the 14th day of development.
If the methods developed by Zernicka-Goetz’s team are shown to be successful with human stem cells in the future, they could also be used to guide development of synthetic organs for patients awaiting transplants.
“There are so many people around the world who wait for years for organ transplants,” said Zernicka-Goetz. “What makes our work so exciting is that the knowledge coming out of it could be used to grow correct synthetic human organs to save lives that are currently lost. It should also be possible to affect and heal adult organs by using the knowledge we have on how they are made.
“This is an incredible step forward and took 10 years of hard work of many of my team members – I never thought we’d get to this place. You never think your dreams will come true, but they have.”
Professor Magdalena Zernicka-Goetz has made an incredible scientific breakthrough.
The creation of synthetic mouse embryos in a test tube that develop brains and beating hearts, starting only with embryonic stem cells, is the culmination of a decade’s work.
Magda explains:
I’m fascinated by the mystery of how embryos work. Every embryo follows a similar journey: one cell becomes many, then they communicate with each other and arrange themselves to form a structure that will provide a blueprint for all adult body parts. But how do embryo cells decide their fate, how do they know where to go and what to do? How do they form the right parts in the right place at the right time?
Building the first ‘synthetic embryo’ models was a process we achieved step by step. Setting out, we knew that embryonic stem cells could be cultured indefinitely in the lab, and that when they’re injected into an embryo they can potentially contribute to any tissue in the adult organism. The challenge was to guide them to develop into a complete embryo. In addition to the embryonic stem cells we used two kinds of extraembryonic tissue: one of which forms the placenta and the other a sac in which the embryo develops. These tissues are very important, as they send signals to the embryo to develop all its parts at the right time and in the right place.
Combining stem cells representing each of these three types of tissue is easier said than done. We had to find an environment where all three distinct cell types could grow and communicate with each other. And we had to find the right proportions of each cell type, and add them in the right sequence. Once we established these basic principles, the stem cells did the rest: they self-organized to progress through successive developmental stages until they had beating hearts and the foundations for a brain.
The key to our achievement was thinking outside the conventional box. The majority of embryo model studies focus on embryonic stem cells, but don’t consider the significant role of extraembryonic cells. We mixed the right proportions of both embryonic and extraembryonic stem cells. Extraembryonic cells signal to embryonic cells through different means, by chemical signals but also mechanistically ‘by touch’. Our studies are helping to understand these signaling events.
We are developing an analogous model of the human embryo, to understand the mechanisms behind crucial processes that would be otherwise impossible to study. This is important because the great majority of human pregnancies fail at this developmental stage, due to causes that we don’t understand. It will also allow us to identify factors permitting development of healthy human tissues as they form different organs.
Creating the new ‘synthetic embryo’ has taught us a lot about the mechanisms by which the embryo builds itself. We learned how the extraembryonic tissues direct the embryonic stem cells along the right pathways to signal formation of the correct structures; how cells move between compartments as the multi-layered body plan arises; and how this correctly sets the scene for neurulation — the process where tissue folds to form the neural tube and, in turn, the brain and spinal cord.
This model gives us access to the developing structure at a stage that’s normally hidden from us, when the tiny embryo implants into the mother’s womb. Our model does not have to implant to develop, so it remains completely visible to us, allowing us to see the embryo’s progression through that developmental stage. This accessibility allows us to manipulate genes to understand their developmental roles in a model experimental system.
It’s certainly true that carrying out this type of work requires passion and resilience. I grew up in Poland under a Communist regime, which meant that traveling wasn’t allowed and thinking differently was not encouraged. There was immense social pressure to conform, and a lot of us rebelled against that. A silver lining of this was a desire to think independently and to persevere despite discouragement. That shaped me as a scientist too.
When I started my research group in Cambridge, I established ways to study the ‘developmental black box’ — the development of the embryo at the time of implantation. My mentors had discouraged me from pursuing it during my PhD because they were concerned it would be difficult to shine light inside this ‘box.’ But I was so taken by the question of how the embryo self-organizes that I didn’t give up and, inch by inch, we have worked our way forward.
My advice to all young scientists is to follow your heart. Study a topic that inspires you, and choose an advisor who can be supportive of your style of work. In my opinion, it’s important to guide young scientists in the lab, but also to give them space to explore their individuality. My experience is that the challenges for female scientists increase as they progress through their careers. At later stages, it’s critical to have mentors who understand not only science but also how to balance it with everyday life, including starting a family.
During my own pregnancy, I was shocked when an early screening showed abnormalities. The sampling was of extraembryonic cells so I waited for the amniocentesis, which samples fetal cells that have fallen into the amniotic fluid. These were normal, which put my mind at ease. The experience led me to study mosaic aneuploidy — a condition in which the embryo has cells with the wrong number of chromosomes alongside chromosomally normal cells. Incredibly, we found that these abnormal cells can be eliminated, and the normal, healthy cells compensate for their absence. For some reason, this mechanism doesn’t operate in the tissues that build the placenta, and we’re still trying to understand why and how.
Science is demanding, it’s hard work and it takes away most of your waking hours. I switch off by watching films — I watch a lot of foreign films in Polish, French, and Danish, and documentaries and art films. But when I want to lose myself in another narrative, I watch dramas. I’m also a recent convert to gardening, where I can encourage the successful development of other life forms!
It is an incredible feeling and a privilege to have this direct insight into the origins of a new life. It’s like discovering a new planet that we didn’t know existed.
For more on this research, see Scientists Grow “Synthetic” Mouse Embryo With Brain and Beating Heart.
Reference: “Synthetic embryos complete gastrulation to neurulation and organogenesis” by Gianluca Amadei, Charlotte E. Handford, Chengxiang Qiu, Joachim De Jonghe, Hannah Greenfeld, Martin Tran, Beth K. Martin, Dong-Yuan Chen, Alejandro Aguilera-Castrejon, Jacob H. Hanna, Michael Elowitz, Florian Hollfelder, Jay Shendure, David M. Glover and Magdalena Zernicka-Goetz, 25 August 2022, Nature. DOI: 10.1038/s41586-022-05246-3
A 30-year-old man who has fathered multiple children across the globe has revealed the newest way he’s donating his sperm – through IVF.
Kyle Gordy, from California, is known online for his controversial career as a sperm donor and is the biological father of 49 children across the globe.
In a bid to help struggling families, he offers his services for free and is often inundated with messages from women on Instagram, who want to have his child.
He recently revealed how he keeps his sperm in ‘tip top’ shape by eating more protein, such as fish and beans, as well as organic greens – and claims he’s helped 12 more families conceive.
Now, in a first for the social media star, he’s tried a new method of donating his ‘tadpoles’, revealing that he has fathered his first child via vitro fertilization (IVF) after being approached by a woman online.
In the past, Kyle has only ever donated his sperm by giving it to women to use for artificial insemination, or by having sex with them, which he previously said accounts for roughly 10 per cent of donations.
However, his latest donation is a first in that his sperm will be used to fertilize eggs and the resulting embryos will be frozen for a year until the woman is ready to have a baby.
Kyle Gordy, 30, from California, is known online for his controversial career as a sperm donor and is the biological father of 49 children across the globe
Kyle with one of the children he helped conceived through sperm donation. He admitted many of the women he dated have not approved of his interest in donation
‘She could’ve gone to the sperm bank if she wanted to, but she’d rather do it with me,’ Kyle said.
‘She likes the fact she’s able to see me and talk to me, rather than being a random number on a vial.
‘Also, the procedure is very expensive, so at least she was able to save some money by getting me to donate for free.
‘I think she heard about me through the grapevine, but she said she really likes me and that she’s a doctor, which is great for me, as this shows she’s very well-educated.’
As he’s a self-proclaimed science fanatic, he was excited to go through the process and gain an understanding of how the treatment works.
However, there were many stages involved which he doesn’t usually do – such as cancerous tests and multiple phone calls.
He said: ‘I had to undergo a HTLV test, which I had never heard of before, which tests for a virus that can cause leukaemia and lymphoma.
‘This type of virus is spread by sharing syringes and needles or through blood transfusions and sexual contact.
The serial sperm donor had to lie and pretend he was the woman’s boyfriend in order to go through the procedure
Kyle has operated through straight forward sperm donation, but this time around, he is doing it via in vitro fertilizations for the first time ever
Kyle claims he consumes a high protein, organic diet in order to increase his fertility and the potency of his sperm
In order to donate via IVF, Kyle had to undergo several tests, including cancerous tests, and pretending he was the woman’s boyfriend
The donor, who started donating sperm for free in 2014, said he only wants to make people happy by donating his sperm
‘Especially due to my hobby, as well as because this can transfer from mother to baby through birth or breast-feeding, it was important to have this done.
‘I had an initial phone consultation to discuss the logistics, where they told me I had to do my ‘business’ at a hotel, before donating to the clinic.
‘It’s quite uncomfortable to do this at a clinic, so I was pleased.
‘However, we had to lie and tell them we’ve been together for three months and that I’m doing this as a gift for her birthday.
‘In our emails and phone calls, we’re classed as in a relationship – as if we didn’t, this would have been so much more expensive.’
On 3 August, the eggs will be fertilised with Kyle’s sperm and the resulting embryos will be frozen for a year, until she’s ready to have a baby.
Now, he plans on carrying out the process again in future to help families further – and has a few women already interested.
Kyle added: ‘I’ve spoken to a few more ladies who would like to do this with me, including a former Playboy playmate.
‘I would be happy to do whatever process, as long as it makes people happy and that’s what they want – I have no issues.’
Previously, he shared that despite being inundated with attention from women, he has struggled with dating.
He believes women only approach him because they want a baby and that many who are interested in a relationship, don’t agree with his hobby.
He said: ‘Unfortunately, most women aren’t interested in dating me.
‘Although I’ve had a few women interested in a possible relationship, it never goes anywhere – but if a special lady comes along, I’d be happy to indulge.
‘I have accepted my decision to donate sperm, but I’ve realized that my dating may never be the same as it once was.
‘If I really like them and we’re compatible, I possibly would give it up though.’
In the years since the 1859 publication of “On the Origin of Species,” CharlesDarwin’s ideas about evolution have become foundational to the field of biology. Yet though his ideas were revolutionary, Darwin was not all-seeing — and recent scientific work has revealed a missing element in his theories. That missing piece has to do with sperm.
Indeed, beginning in 1970 and continuing full throttle with new research published earlier this year, biology experiments highlighting “sperm competition” among males are filling in some of the blanks left by the great 19th-century evolutionary scientist. As it turns out, there are evolutionary battles raging in microscopic, behavioral, and physical fields. These skirmishes are about the rights and abilities of rival males to impregnate females.
Darwin used the term “natural selection” to describe the ability of genetically lucky organisms to survive long enough to procreate under environmental conditions that kill others. Animals’ supreme and universal urge to send their DNA into subsequent generations drives evolution. Indeed, to them, it is the very meaning of life. Copulation is how animals satisfy their urgent evolutionary impulse. And for almost all species of multicellular animals, procreation requires that sperm meets egg.
In 1871, twelve years after the publication of “Origin,”Darwin’s “The Descent of Man and Selection in Relation to Sex” made clear that getting sperm to meet egg relies on “sexual selection.” By that term, he meant the preference in one sex for certain attributes in the other. For example, male peacocks with spectacularly feathered tails get sexually selected more often to copulate with fertile females than do less well-ornamented males. Stags with big antlers score more often than stags with small ones.
As world-enlightening as Darwin’s ideas of natural and sexual selection were, there’s a tiny whiff of failure about him as a scientist. Brilliant as he was, he never realized that natural selection and sexual selection aren’t quite enough to explain evolution.
The piece of the evolutionary puzzle Darwin missed
In many species, females take more than one mate during a breeding cycle. (The technical term is that they are “polyandrous.”) For males, this means that successfully copulating isn’t a guarantee that they’ve fertilized eggs. A rival might get to those eggs instead.
Some modern scholars consider Darwin’s failure to recognize polyandry as the wrench jamming up the works of evolution to be one of his biggest oversights.
Here are some of the disruptions to the simple “sperm + egg = baby(ies)” equation that polyandry creates. Say, for example, that multiple males have copulated with the same fertile female. Probably at least one of those males will impregnate her.
But which one?
If she’s carrying more than one egg (and some insects carry hundreds), many males might get to be biological fathers. Some males will probably end up fertilizing more eggs than others, and some may not get to fertilize any at all. Usually, a competition of sorts determines who fertilizes what and in what number. The battle can happen on a microscopic scale, with immediate physiological changes to semen and sperm quality. On the other hand, behavioral adaptations may give an animal his needed edge. (Sometimes, to the casual human eye, these behavioral adaptations can seem impossibly weird.) Even physiological adaptations can boost a male’s chances. (Physical adaptations don’t happen on the spur of the moment during sex like physiological changes to sperm do. They evolve over millions of years.)
Dr. Parker noted that, usually, the last male to inseminate before the female drops her sac in dung wins. He becomes the biological father of around 80% of the eggs.
As a group, the adaptations are called “sperm competition.” The first evidence of sperm competition was identified by Dr. Geoff Parker of the University of Liverpool. His 1970 research described mating behavior in polyandrous yellow dung flies (Scatophaga stercoraria, common in Northern Hemisphere pastures). Females copulate with many males, all while carrying the same egg sac. Dr. Parker noted that, usually, the last male to inseminate before the female drops her sac in dung wins. He becomes the biological father of around 80% of the eggs.
A male of any species can only make so much sperm in a day or maybe even a lifetime. Since 1970, Dr. Parker and others have found that males in polyandrous species spend sperm prudently. For the yellow dung fly, sperm is best spent on virgins. Some male insects boost their paternity chances by flooding only one female with sperm. Still others spread sperm promiscuously, and so on.
Nursery web spiders
Perhaps because they’re easy to catch and breed, much of the research about sperm competition has been done on spiders. February 2022 work from biologists at Ludwig Maximilian University in Munich and Aarhus University in Denmark shows the benefit to mating males of long copulations. When a male nursery web spider (species Pisaura mirabilis, found all over Europe) offers a female a “nuptial gift” of a silk-wrapped bug, she allows him to copulate. What’s more, she lets him continue to flood her receptacle with sperm for as long as the proffered meal lasts. In an email, co-investigator Dr. Cristine Tuni explained the logic of this adaptation. The spider’s ejaculate doesn’t arrive as a brief, happy burst and then stop. Rather:“In this species, sperm is transferred continuously over time from his copulatory organ into hers,” Tuni says. “So, the longer a male has his organ coupled to a female organ, the more sperm is transferred. The relationship is basically linear.”
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One egg sac can carry hundreds of eggs. Because of this, any male wanting a big bang for his f**k probably intuits that size (of the gift) matters. Pumping as much semen as possible can help send his DNA on its way.
Malabar spiders
The Malabar spider (Nephilengys malabarensis, found in Asian rain forests) wields a far more dramatic sperm competition adaptation. Each male has two genital appendages extending from behind the mouth. As semen pulsates out of one, the spider detaches it and leaves it inside the female’s receptacle. Even severed like that, the genital continues to ejaculate. Meanwhile, it also plugs the receptacle, making it difficult for another male to get a genital in. Ready to fend off anyone who tries, the mating male stays on the web near the female. Unfortunately for him, each female’s semen receptacle has two openings. He has only plugged one. This means that, if a rival approaches, the mating male will have to fight fiercely to keep him at bay. To that end, and while ejaculation from the abandoned genital continues, many males eat their only remaining genital.
Of course, that seems like a counter-intuitive strategy. Why get hungry at that very moment? Why hurt yourself right when you may need all the energy you can muster?
A team of biologists from several institutions in Europe and Asia seem to have an answer. They compared the battle survival rates of spiders who’d severed one genital to those of spiders who’d severed one and eaten the other. Additionally, they tested the battle survival rates of genitally intact males. The name of the team’s paper — “Eunuchs Are Better Fighters” — says a lot about why, under duress, a Malabar spider would eat its only remaining genital.
RELATED: How testosterone and oxytocin hormones influence male behavior
God knows why that’s true, but apparently it is. What’s more, turning himself into a eunuch is not where a Malabar spider’s sperm competition adaptation ends.
Immediately after mating, a eunuch male usually lets the female eat him. Why not? Doing his best to fulfill his biological imperative to guarantee the intergenerational survival of his DNA, he has left himself incapable of copulating. At least any eggs he has already fertilized will benefit from his calories and protein.
Sperm competition in mammals (including humans)
Coyotes and other canines have an anatomical sperm competition adaptation. A bulbous gland at the base of the penis inflates, locking it inside the vagina and giving ejaculated sperm time to reach the female’s eggs before another male mounts the female. This doesn’t necessarily mean that the first canine’s sperm will fertilize the entire littler. Even so, the arrival time of a canine’s sperm may make a critical difference in whether he can fertilize at least one egg.
In great apes, a primary adaptation is semen volume, which is reflected in testes size. For example, silverback gorillas are not particularly polyandrous. Typically, several females are sexually dominated by a single male. With no need to out-compete the inseminations of other males, gorillas have small testes relative to their enormous bodies.
Female chimps and bonobos, on the other hand, are decidedly polyandrous. Indeed, bonobos are notorious libertines; a fertile female chimp might copulate three or four times an hour with different males. Both males and females copulate with same- and different-sex partners freely and joyfully as a way to have fun, make friends, soothe tempers, and (yes) make babies.
Humans, too, are great apes. In general, women are less polyandrous than chimps and bonobos and more polyandrous than gorillas. Relative to their body sizes, men’s testes are not typically as large as those of chimps and bonobos and they’re not as small as those of gorillas.
In 1993, environmental biologists R. Robin Baker and Mark A. Bellis found one way in which men may have evolved to help sperm meet egg. Testing 35 men, they found that the ones whose mates had recently been out of their sight had more sperm in their ejaculate.
Certainly, many modern humans have intercourse for reasons other than procreation. Providing sexually active people with ways to avoid pregnancy is a multi-billion-dollar industry. Even so, humans’ mating behaviors may be driven to some extent by the same “meaning of life” urge to ensure the survival of their DNA that motivates other animals.
In 1993, environmental biologists R. Robin Baker and Mark A. Bellis found one way in which men may have evolved to help sperm meet egg. Testing 35 men, they found that the ones whose mates had recently been out of their sight had more sperm in their ejaculate. The biologists reasoned from the data that a partner’s temporary absence might make a man uncertain about her fidelity. Niggling suspicion that his sperm has to compete with that of other men might create a physiological response increasing sperm count.
In more recent years, Dr. Leigh Simmons of the Centre for Evolutionary Biology at the University of Western Australia has run a series of experiments with carefully controlled parameters. He and Dr. Sarah J. Kilgallon demonstrated that the very idea of sexual rivals can trigger sperm changes. They showed one group of men pornography involving one woman and two men. A second group saw pornography involving only women. The two researchers found that the sperm produced by men who viewed pornography involving one woman and two men swam faster.
At least one possible sperm competition adaptation in humans is anatomical. Simmons and collaborator Dr. Samantha Leivers have proposed that the piston shape of men’s penises may have evolved to help men rid their mates’ vaginas of a rival’s previously deposited sperm. With a flat-bottomed head and a shaft that is narrower at top than bottom, the human penis can scoop out semen each time it momentarily withdraws from a vagina in preparation for the next thrust.
Males in polyandrous non-human species can ramp up sperm volume, count, and vitality in response to the presence of rivals.
Meanwhile, Simmons and many others have acknowledged mate guarding behaviors like sexual jealousy as a primary sperm competition adaptation. Surprisingly, work in the Simmons lab has also demonstrated that mate guarding behaviors like jealousy work against production of higher quality sperm. In 2014 in the peer-reviewed journal PLOS ONE, Simmons and Dr. Gillian Rhodes reported:
We found that men who performed fewer mate guarding behaviors produced higher quality ejaculates, having a greater concentration of sperm, a higher percentage of motile sperm and sperm that swam faster and less erratically.
Score one, perhaps, for the idea that the ideal mate is more courtly than boorish.
Sperm competition adaptations and human infertility
The Urology Care Foundation reports that up to 50% of infertility issues among human couples are linked to problems with male semen.
Males in polyandrous non-human species can ramp up sperm volume, count, and vitality in response to the presence of rivals. For humans, even the thought of polyandry can jack up a man’s sperm quality. Considering all of that, might turning the knob way up on polyandry as a real or imagined stimulus rocket launch the get-up-and-go of any given man’s sperm? Might overt and rampant promiscuity on the part of a woman help her man with his fertility problem?
That’s a bit of a sci-fi scenario, but by email and on Zoom I asked Dr. Simmons what he thought about it. By way of an answer, he told me about a body of work by Drs. Mariana Wolfner (Cornell University), Tracy Chapman (University of East Anglia), and Stuart Wigby (University of Liverpool). It shows that a protein called “sex peptide” in the ejaculate of male fruit flies (Drosophila melanogaster, originally an African species)diminishes a female’s sex drive. This reduces the likelihood that, once inseminated, a female will let additional males try to fertilize her enormous sac of eggs.
Unfortunately for the female of that species, sex peptide shortens her lifespan.
The research to which Dr. Simmons referred raises the specter of unpredictable results for humans of a modern reproductive strategy reaching to ludicrous lengths to boost sperm quality.
That said, there’s probably a second problem with my idea of operatic promiscuity, or at least there’s a problem with asking a well-respected scientist to weigh in on it. Generations of anthropologists have made clear that, across cultures, women sometimes take more than one mate. Even so, most women wanting to conceive take pains to seem to do so as part of a couple, harem, or intentional family. Potential risks to women who use exaggerated promiscuity to boost a male partner’s fertility have not been well-studied. Maybe, given the outré arrangement that would be needed to conduct such an experiment, the risks never will be studied at all.
With no easy sperm competition fixes to the infertility problem that 10 to 15% of American couples face, many couples are unable to revel in the meaning of life as Darwin’s natural selection theory defined it. They might take comfort in the realization that philosophers have wondered, without resolution, about “why life?” for millennia. They might also find comfort — or at least comic relief — in the 1983 Monty Python film, “The Meaning of Life.”
In particular, one of the movie’s songs might help boost moods. Granted, its lyrics aren’t about sperm competition per se. They bash narrow-minded ideas about fertility and masturbation. Even so, “Every Sperm is Sacred” might work as a fertility anthem. It could be sung in biology labs and bedrooms as well as in jungles, on spider webs, and near bowls of fruit everywhere.
Read more on the search for extraterrestrial intelligence:
A jury in Colorado awarded $8.75 million on Wednesday to the plaintiffs in a civil lawsuit who accused a former fertility doctor of using his own sperm to impregnate at least a dozen women via artificial insemination over more than two decades.
The judgment was awarded to Cheryl Emmons, her husband and two of her daughters, who their lawyer Patrick Fitz-Gerald said had been surreptitiously fathered by the doctor, Paul B. Jones.
The Emmonses and seven other families filed a lawsuit in October 2019 against Dr. Jones and the clinic where he worked, Women’s Health Care of Western Colorado, on claims of medical negligence, lack of informed consent, fraud, negligence misrepresentation, breach of contract, battery, and extreme and outrageous conduct, according to the lawsuit.
Five of the families settled for an undisclosed amount before the case went to trial, Mr. Fitz-Gerald said. Two other claims against Dr. Jones are still active.
Because the Emmonses filed more claims against Dr. Jones than against the clinic, he is expected to pay a vast majority of the $8.75 million award, Mr. Fitz-Gerald said.
Dr. Jones’s lawyers, Nicole Marie Black and Nancy L. Cohen, did not immediately respond Thursday to emails or phone calls seeking comment. But in 2019, around the time the lawsuit was filed, Dr. Jones refused to tell a reporter from KUSA in Denver whether he had fathered the children named in the lawsuit.
“I don’t deny it; I don’t admit it,” he said at the time.
He gave up his physician’s license in November 2019, days after the families filed the lawsuit, according to state records.
Ivan Sarkissian, a lawyer for Women’s Health Care of Western Colorado, where Dr. Jones worked, did not immediately return emails or calls on Thursday.
Dr. Jones, Ms. Emmons’s former obstetrician and gynecologist in Grand Junction, Colo., was believed to have fathered at least 17 children with 12 women from 1975 to 1997, Maia Emmons-Boring, one of Ms. Emmons’s daughters, said on Thursday.
In 1979 and 1984, Dr. Jones impregnated Ms. Emmons by artificial insemination after suggesting that he would find a doctor or medical student to be her sperm donor, Ms. Emmons-Boring said.
He never told the family that he was the one providing the sperm sample, Ms. Emmons-Boring said. Dr. Jones, now 83, even helped deliver both Ms. Emmons-Boring and her sister Tahnee Scott.
Ms. Emmons-Boring had never questioned that the man who raised her was not her father until a series of events that began after she took a DNA test from Ancestry.com.
In 2018, after Ms. Emmons-Boring took the test, she said she received a message from a woman who believed they were half-siblings. She did not believe the woman at first, but then she did some digging.
Her parents then told her for the first time that she and her sister had been conceived using artificial insemination. She spent weeks constructing a family tree “until it ran into Dr. Jones,” she said.
She messaged five other half-siblings she had found online, who “were all shocked and disgusted” by the news, said Ms. Emmons-Boring, 41.
Maia Emmons-Boring with her sister Tahnee Scott.Credit…The Emmons family
A few weeks later, they called Mr. Fitz-Gerald’s law firm, Driskell, Fitz-Gerald & Ray. Eight families eventually filed the lawsuit against him and the clinic, Mr. Fitz-Gerald said.
Dr. Jones was never charged with a crime in connection with the artificial insemination, according to Daniel P. Rubinstein, the district attorney from the 21st Judicial District Attorney’s Office in Mesa County, Colo. At the time, Mr. Rubinstein said, it was not a crime in Colorado for a doctor not to disclose the identity of a sperm donor.
After news of Dr. Jones’s actions spread through Colorado, the state passed a law in 2020 that made it a felony if a health care provider “knowingly uses gametes” from a donor without a patient’s consent.
At least 50 fertility doctors in the United States have been accused in recent years of donating sperm after commercial DNA testing became more widespread.
Ms. Emmons-Boring said she was working with Colorado lawmakers on one of the country’s first laws that would offer certain protections to children conceived as a result of fertility fraud.
For now, she said, she “deals with a lot of guilt” over the fact that she ever took a DNA test.
“It’s turned so many lives upside down because I took that test,” she said.
She is also concerned that, because Dr. Jones fathered so many children in one area, some of them may date or marry one another.
Ms. Emmons-Boring said that some of her half-siblings believe Dr. Jones may have passed down a gene for cystic fibrosis, but they cannot know for certain because he has refused to share his medical history with them.
“It would be nice,” she said, “if he showed some sort of compassion.”
Testicular pain, erectile dysfunction, reduced sperm count and quality, decreased fertility are direct consequence of infection, new study shows.
Multiple tissues of the male genital tract can be infected with https://www.youtube.com/watch?v=eVRnxBtTpAM
The evidence that infection with SARS-CoV-2 can negatively impact male sexual health and fertility is increasing every day. But scientists didn’t know the reason and wondered if the cause was fever and inflammation.
“We just didn’t understand why it had this negative impact until this study,” Hope said. He noted viruses such as mumps, Ebola, Zika, SARS-COV-1, and other viruses also can infect tissues of the male genital tract and negatively impact fertility. Mumps infection is well known to potentially cause male sterility.
The new study shows how the virus can cause pathology in the prostate, penis, testicles, and testicular vasculature (blood vessels), Hope said.
The study is posted as a preprint on bioRxiv, meaning it should be considered preliminary research until it is published in a peer-reviewed journal.
“Even if this is only a small percentage of the infected, it represents millions of men who may suffer from a negative impact on their sexual health and fertility,” Hope said.
Clinical studies suggest 10% to 20% of SARS-CoV-2-infected men have symptoms related to male genital tract dysfunction. This suggests tens of millions of men who have been infected with SARS-CoV-2, especially those who had severe
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Testicular pain, erectile dysfunction, reduced sperm count and quality, decreased fertility are direct consequence of infection, new study shows.
Multiple tissues of the male genital tract can be infected with
The evidence that infection with SARS-CoV-2 can negatively impact male sexual health and fertility is increasing every day. But scientists didn’t know the reason and wondered if the cause was fever and inflammation.
“We just didn’t understand why it had this negative impact until this study,” Hope said. He noted viruses such as mumps, Ebola, Zika, SARS-COV-1, and other viruses also can infect tissues of the male genital tract and negatively impact fertility. Mumps infection is well known to potentially cause male sterility.
The new study shows how the virus can cause pathology in the prostate, penis, testicles, and testicular vasculature (blood vessels), Hope said.
The study is posted as a preprint on bioRxiv, meaning it should be considered preliminary research until it is published in a peer-reviewed journal.
“Even if this is only a small percentage of the infected, it represents millions of men who may suffer from a negative impact on their sexual health and fertility,” Hope said.
Clinical studies suggest 10% to 20% of SARS-CoV-2-infected men have symptoms related to male genital tract dysfunction. This suggests tens of millions of men who have been infected with SARS-CoV-2, especially those who had severe
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js = d.createElement(s); js.id = id;
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