Humans are not Naked Mole Rats and Can't Make Eggs in Adulthood

Dispelling the false claims of egg regeneration

I’ve lost count of the number of times that I’ve been asked about this post on Instagram that claims that women don’t have a finite number of follicles (aka eggs), but rather they keep making new ones in adulthood. 

I thought it wasn’t enough of a “thing” to write about, but yesterday I was sent another Instagram post making the same claims using much of the same “data” from a self-declared public figure and self-styled wellness expert and fertility detective.

It seems the false idea that ovaries don’t have a finite follicular lifespan is becoming a thing, and so here we are.

Before we get started, please don’t engage with these accounts, it only increases their engagement and the algorithm just drives even more eyeballs to them. My advice is to simply block people who share this kind of disinformation, it is the most evidence based way to protect yourself.

And a word to anyone who thinks it is mean to “call people out.” Correcting misinformation and disinformation is not calling people out, it’s being an expert and correcting the record. You know what is mean? Giving people false false hope that their ovaries can keep making eggs in adulthood.

I Have Questions

If humans are, right now, making more follicles as they age, then why does everyone have menopause? Why has the average age of menopause been stable for more than two thousand years? Why don’t we see lots of spontaneous pregnancies at age 50 and beyond?

Why??????

My guess is the people who want you to believe that humans can keep making follicles until they die have a service to sell you to help you develop or nurture that process. You know, a secret “they” (meaning medicine) don’t want you to know. Because of course, if there were a diet or coaching service to improve the health and longevity of ovarian follicles we doctors would be sure to hide it from you (insert massive eye-roll).

Kidding and sarcasm aside, there is real harm here. One, in wasting money on untested and often ludicrous supplements, diets, and coaching services. Two, it could lead some people to delay seeking care. Imagine you are 39 years old and having difficulty getting pregnant, but instead of contacting a board certified reproductive endocrinologist you contact a wellness expert because her posts on Instagram seemed authentic and insinuated you could have a baby without injections and procedures because you are still making new eggs even as you age? Two years go by, you don’t get pregnant from the diet or acupuncture or herbs (and spices) and so you finally seek care from a qualified medical professional and now you have even fewer options. Perhaps your window for conceiving without expensive therapy has closed. And the final harm here is the cruelty. Implying that a diet or lifestyle change can release the true potential of your ovaries implies that you have been doing something wrong all this time and you alone are the cause of your infertility or menopause. 

There is also real harm here for the menopause community. I’ve seen women spend a lot of money on tests and supplements and protocols designed to “prevent” the end of ovarian function or to “kick start” the ovaries back into action. Apparently there are even courses for learning the “root cause” of menopause and how to prevent it. 

Because of course there are. Sigh.

So what’s the deal here? 

Misinterpretation of Animal Studies

Some of the information in these two Instagram posts and others like them are cherry picked and some of it is misinterpreted and some is not accepted by the general medical community. For example, both these content creators appear to cite a “2023 study on naked mole rats” that shows the “phenomenon of new eggs appearing in the ovaries of adult female mammals” and the implications is this is somehow applicable to humans

I understand how this might sound convincing to someone who doesn’t know the science. Mammals are mammals, right? Well, naked mole rats are very different from humans in many ways. Read the Wikipedia page for fun after you finish this article. You will not be disappointed. It’s jaw dropping, and you will learn why they are most definitely not called sharply dressed rats. All I can say is, evolution, “That’s Incredible!”

Naked mole rats have a unique reproductive physiology, because they make ALL of their follicles (eggs) after birth, unlike humans who make ALL of their follicles before birth. Also, most female naked mole rats are workers and don’t breed, only the queen does and with a small selection of males. The queen has multiple litters a year with an average of 13 pups per litter over an average lifespan of 32 years (which is wildly long for a rodent). 

Naked mole rats also have a deficiency in substance P, an important neurotransmitter for pain. Many things that would cause us to feel pain don’t affect the naked mole rat at all. It's a pretty cool phenomenon and worthy of study, but it shouldn’t be used as evidence for why humans shouldn’t feel pain! 

Naked mole rats and humans have had very different evolutionary pressures and are not at all a good comparison group for humans. It’s true that naked mole rats might be a good model to learn more about human ovarian function, because their ovaries do after birth what ours do before birth and are far easier to access for study. However, the idea that someone would compare human reproduction to that of the naked mole rat to make their point is ridiculous on the face of it.

Controversial Research

About twenty years ago there was a buzz in reproductive medicine that ovarian stem cells had been discovered that could make new follicles. 

Some initial data emerged in 2002 that suggested egg regeneration may have happened in a mouse study. In this study, mouse ovaries were exposed to chemotherapy to kill the eggs, but instead, it seemed like more eggs were appearing. Meaning, the ovary was making new eggs! This data was eventually published in 2004 and made a splash at the time, and the conclusion was somehow the mouse ovaries were regenerating eggs from germline stem cells. And then another group suggested that follicle renewal might happen in mice. And then further research was published suggesting these stem cells had been identified in human ovaries and they could be stimulated to produce new eggs. 

Might this unlock new therapies for infertility and menopause? Was a major tenet of ovarian physiology incorrect? For a period of time this was a very hotly debated and researched topic. 

Several other researchers have not been able to reproduce the human data, finding no germline stem cells (cells that could become new follicles) in human ovaries and they have also not been found in primate ovaries (our closest relatives with similar ovarian function). And so the current belief is that humans do not have stem cells in the ovaries, and so all the follicles we have are those we developed by about 20 weeks as a fetus.

And here’s an important aside, even if these germline stem cells did exist it doesn’t support the claim that women are today making new eggs in adulthood, because that would have already been happening. We wouldn’t see fertility drop with age. Instead, for these stem cells to make new eggs manipulation in the lab would almost certainly be required.  

The End of Ovarian Reproductive Function is Inevitable

Enough with the bad mole rat comparisons.  What really happens in humans? Primordial follicles (immature eggs in hibernation) develop as a fetus, and by 20-22 weeks a fetus has all the primordial follicles it will ever have, about 5-6 million. Follicles begin to decline rapidly from that point onwards and at birth there are only 300,000-400,000 that remain.

Over time, primordial follicles continue to be lost, because some are regularly pulled out of hibernation and enter what is called the growing pool. This is a long process that takes months, but eventually some make it to the antral phase. Before menstruation starts there is no signal for these follicles to develop further, so they disintegrate. After menstruation has started, signaling from the brain triggers some of these antral follicles to grow and start the final trek to ovulation. The loss of follicles starts to accelerate around age 37, which lines up with the age-related decline in fertility. Once there are about 1,000 or so follicles left, ovulation is no longer possible. 

Genetics are mainly responsible for the amount of primordial follicles and their rate of loss, but environmental factors do play a role. For example, smoking damages follicles, and reduces their health and/or quantity. And those who have more pregnancies may have a slowing of the recruitment of follicles out of hibernation due to the high levels of progesterone during pregnancy. 

Some people wonder if an earlier puberty means an earlier menopause, but the answer is no. Whether you start menstruating at 8 or at 12 years of age, primordial follicles are still being pulled out of hibernation on a regular basis and then disintegrating. The only difference when menstruation starts is now the brain can trigger some of the antral follicles to enter the menstrual cycle and potentially ovulate. 

What about hormonal birth control? If ovulation is suppressed with contraception, does that delay menopause? While ovulation is suppressed, the recruitment of primordial follicles out of hibernation into the growing pool isn’t affected. Meaning the ovarian metronome keeps chugging along, but the hormones suppress messaging from the brain, so these follicles stop on day 2-3 of the menstrual cycle and don’t develop any further. This means follicles are developing and disappearing whether you are taking the pill or the patch of the ring or have the implant or use the shot or not. 

Hormonal contraception has been around for over 50 years, so if it delayed menopause we’d know. 

To Recap…

There is no evidence that humans can keep making new eggs in adulthood.

The evidence that the potential is there (meaning germline stem cells) is not supported by the bulk of the research and is considered highly controversial.

Also, if an “all natural” and “unprocessed” and “toxin free” diet really did extend the lifespan of human follicles, then why before the 1900s when everyone ate a local, “all natural,” “unprocessed diet,” was the average age of menopause still around 50? Inquiring minds want to know.

References

Marco Conti, R. Jeffrey Chang. Chapter 125 - Folliculogenesis, Ovulation, and Luteogenesis,

Editor(s): J. Larry Jameson, Leslie J De Groot, David M. de Kretser, Linda C. Giudice, Ashley B. Grossman, Shlomo Melmed, John T. Potts, Gordon C. Weir. Endocrinology: Adult and Pediatric (Seventh Edition). W.B. Saunders, 2016, Pages 2179-2191.e3, ISBN 9780323189071.

Wagner, M., Yoshihara, M., Douagi, I. et al. Single-cell analysis of human ovarian cortex identifies distinct cell populations but no oogonial stem cells. Nat Commun 11, 1147 (2020). https://doi.org/10.1038/s41467-020-14936-3.

Brieño-Enríquez, M.A., Faykoo-Martinez, M., Goben, M. et al. Postnatal oogenesis leads to an exceptionally large ovarian reserve in naked mole-rats. Nat Commun 14, 670 (2023). https://doi.org/10.1038/s41467-023-36284-8.

McGee EA, Hseueh AJW. Initial and Cyclic Recruitment of Ovarian Follicles. Endocrine Reviews 21(2): 200–214.

Masahito Yoshihara, Magdalena Wagner, Anastasios Damdimopoulos, Cheng Zhao, Sophie Petropoulos, Shintaro Katayama, Juha Kere, Fredrik Lanner, Pauliina Damdimopoulou. The Continued Absence of Functional Germline Stem Cells in Adult Ovaries. Stem Cells, 2023, 41, 105–110 https://doi.org/10.1093/stmcls/sxac070

Fan X, Bialecka M, Moustakas I, et al. Single-cell reconstruction of follicular remodeling in the human adult ovary. Nat Commun. 2019;10(1):3164. https://doi.org/10.1038/s41467-019-11036-9

Wang S, Zheng Y, Li J, et al. Single-cell transcriptomic atlas of primate ovarian aging. Cell. 2020;180(3):585-600.e19. https://doi.org/10.1016/j.cell.2020.01.009.