A series of findings from the Oklahoma Medical Research Foundation could someday lead to extending the female reproductive period.
Menopause officially signals the end of female fertility, but for most women, ovaries begin their downswing around age 35 – years before their menstrual cycle ends.
The driver of that reproductive decline isn’t clear, but recent experiments conducted by OMRF scientists José Victor Isola, Ph.D., Sarah Ocañas, Ph.D., and Michael Stout, Ph.D., offer new clues. And with the upward trend in the mean age of pregnant women in the U.S., the knowledge is critical. According to 2020 data from the Centers for Disease Control and Prevention, nearly 19% of all pregnancies and 11% of all first pregnancies in the U.S. were in women aged 35 years and older.
Isola, Ocañas and Stout demonstrated for the first time that, in preclinical models that correspond to a woman in her mid- to late 30s, a particular type of immune cell accumulates more rapidly in the ovaries.
“Now we can begin trying to understand why this is happening,” said Isola, a postdoctoral researcher in Stout’s lab. “Our findings represent a potential step toward trying to slow the ovarian aging process.”
The experiments also showed that around the same time, inflammation forms in cells that encircle developing eggs. This inflammation complicates the process of an egg maturing to the point it can be ovulated and fertilized.
“We still don’t know which came first – the chicken or the egg,” Stout said. “Are those cells that encircle the egg drawing in all those immune cells, or are the immune cells causing the inflammation? That answer will require additional research.”
Additionally, the researchers found a buildup of collagen in the normally pliable ovarian tissue, causing it to become fibrotic. “This is important,” Ocañas said, “because when the tissue becomes hard and stiff, it makes ovulation of the egg much more difficult.”
Stout’s lab has been studying whether a protein complex called mTORC1 promotes ovarian decline. While the protein plays a significant role in cell division, wound healing and inflammatory responses, its role in ovarian decline is less clear.
Stout now plans to test whether inhibiting mTORC1 reduces inflammation in the cells encircling the egg.
“We’re still in the early stages of discovering why the ovary ages so fast and why it’s one of the first human organs to lose its function,” Isola said. “These experiments provided information that we can build upon.”
The journal Nature Aging recently published the team’s findings.
This research was supported by National Institutes of Health grant No. R01AG069742 to Stout and by grants to Ocañas and Stout from the Global Consortium for Reproductive Longevity and Equality. The Oklahoma City-based Presbyterian Health Foundation provided funding for Stout’s preliminary research.
