Opinion | Ovaries Are Prone to ‘Exhaustion’ and ‘Fatigue.’ Or Are They? – The New York Times


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Ms. Gross is a science journalist and the author of “Vagina Obscura.”
Women, you may have heard, are born with all the eggs they will ever have. It’s one of those factoids that gets repeated ad nauseam in medical textbooks, health magazines and high school biology classrooms.
Sometimes, it is used to awe and inspire: Is it not incredible that at one point, a woman pregnant with a female fetus carries not only her daughter but also the eggs that could one day become her grandchildren — three generations in one body? Other times, it’s used to illustrate the bedrock differences between male and female biology: Ovaries are degenerating organs, prone to exhaustion and fatigue, while testes are hotbeds of renewal, pumping out sperm long into old age.
But what if there is more to the story?
As the traditional tale goes, the ovary is like an hourglass. Starting before birth, egg follicles begin trickling away like grains of sand. A fetus floating in the womb is bursting with as many eggs as she will ever have: 6 million to 7 million. More than three-quarters of them die off before she’s even born. By the time a girl has her first period, only 300,000 to 400,000 remain.
Between the ages of 45 and 55, most women run out of almost all the eggs they were born with. The hourglass is now nearly empty — an event known as menopause. The significance of this event goes far beyond fertility, thanks to the ovaries’ crucial second function: churning out estrogen and progesterone, which support the health of nearly every body system.
The born-with-all-your-eggs mantra has been a linchpin of reproductive biology ever since a study in 1951 established it as scientific dogma. As it’s been told, the story of women’s reproductive life is one of limits and restrictions. The idea that ovaries degenerate and run out of eggs has given rise to the pernicious image of the ticking female biological clock and the larger cultural trope that women lose femininity, vigor and value as they age.
But for the past two decades or so, there have been hints that ovaries may be doing more than we give them credit for. The research is still in its infancy, but some biologists now argue that ovaries appear to have the ability to grow brand-new eggs throughout a woman’s life.
The first modern evidence of this came in 2004, when a team led by the Boston-based biologist Jonathan Tilly found signs of stem cells in mouse ovaries that appeared to be able to develop into new eggs. Five years later, a Chinese research team showed that these stem cells could give rise to healthy mouse pups. In 2012, Dr. Tilly teamed up with the biologist Dori Woods to identify the same stem cells in human ovaries, using small pieces of gonadal tissue removed from patients undergoing gender affirmation surgery.
At this point, the question is increasingly less about whether human ovarian stem cells exist; it’s more about how they behave. Do they contribute to the standing egg pool? Or are they held in reserve, stirring into action only when the ovaries suffer serious injury or damage, as when undergoing certain forms of chemotherapy? Either way, the existence of these cells has the potential to profoundly change our understanding of how the ovaries work.
Yet many leading scientists have been resistant to the new research. When the idea that ovaries could continue to make new eggs came out, other researchers derided it as faulty and premature and a distraction from serious inquiry into ovarian biology. Subsequent research confirming the findings was also greeted with contempt. “Except at Disney World, humans are not large mice,” one critic pronounced after the news of the studies on the mice pups.
It would take several years and dozens more papers for ovarian stem cells to be mentioned in some medical textbooks, where they are still described as controversial. (Some of those papers revealed conflicting data, and some scientists remain unconvinced.)
At some level, the hostility to the possible existence of ovarian stem cells isn’t surprising. Science has a tendency to resist destabilizing new information, at least at first. It took years for neuroscience to accept that human brain cells regenerate, despite evidence that they do so in other species. Today the finding that neurons die and are replaced throughout life is recognized as one of biology’s greatest paradigm shifts, inspiring new possibilities for tackling degenerative conditions like Parkinson’s and Alzheimer’s.
Resistance to the idea that neurons regenerate was due in part to deeply ingrained ideas about human exceptionalism. The mere fact that songbird neurons regenerate, some argued, told us little about how the sophisticated human brain worked. Humans, it was thought, were special. Humans were not birds.
In the case of the ovary, there may be another factor at play: deeply held assumptions about the differences between men and women.
“Cultural biases about women” have long shaped reproductive medicine and reproductive science, said Evelyn Telfer, a reproductive biologist at the University of Edinburgh who has studied ovaries since the 1980s and led a study suggesting that the human ovary may be able to grow new eggs in adulthood. And these biases, “whether conscious or not,” are likely shaping responses to ovarian stem cell research, too, she said.
Biology texts describe men as reproductively prolific. They make hundreds of sperm every time they breathe and keep making them into old age. (Their quality is another matter.) By contrast, ovaries are said to “fail” (despite the fact that they continue to make some hormones after menopause). “The field was so entrenched in the idea that the ovary had no regenerative capacity, period,” said Dr. Tilly. “It came out of decades of the unfailing belief that the ovary was different from the testis.”
But if ovaries regenerate, how do we explain menopause? Traditionally, it’s been defined as simply running out of eggs and ceasing to menstruate — the hourglass metaphor. Ovarian stem cells suggest an alternative possibility. Perhaps it isn’t that ovaries run out of eggs but that the cells that nourish those eggs and pump out hormones to the rest of the body may be too damaged to continue. (This idea is supported by the fact that stem cells have been found in the ovaries of postmenopausal women.)
This scenario suggests interventions we previously couldn’t imagine. First, ovarian stem cells could be stockpiled to make future eggs on demand. Beyond fertility, ovarian tissue grown in a lab and implanted back into a woman could jump-start hormonal function for, say, cancer survivors or women with Turner syndrome. More controversially, the same technology could theoretically be used to delay natural menopause.
These technologies are fraught with medical, legal and ethical hurdles, and future research may not bear out the possibility of human ovaries being able to produce new eggs. (Dr. Tilly holds several patents related to fertility preservation and ovarian tissue bioengineering technologies, five of which he shares with Dr. Woods.) But whether or not it comes to fruition, there’s a broader point here: Increasingly, it’s looking as though the ovaries are one more example of how old assumptions about women have prevented us from a fuller understanding of the female body.
To wit: We now know that the vagina is no passive receiver but a muscular organ lined with billions of microbes that have likely evolved with humans over millenniums. Recent research has shown that the egg is no patient damsel but a dynamic cell that undergoes brutal competition and draws flailing sperm into its orbit. The clitoris is no pea-size nub but a richly innervated structure that extends deep into the pelvis.
These discoveries suggest that the female body may be more resilient, dynamic and expansive than science has historically considered it. To rethink the ovary is to open the door to questioning a whole host of things that everybody knows are “true” about the female body. It is to reimagine how the female body works — and rethink what all bodies are capable of.
Rachel E. Gross is a science journalist and the author of “Vagina Obscura,” from which this essay was adapted.
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