By: Akanksha
When all is said and done, fertility is determined not only by the number of eggs a woman is born with but also by their quality throughout the life. This theory has prompted Hongmei Wang, a 52 year old Chinese biologist who works at the State Key Laboratory of Stem Cell and Reproductive Biology in Beijing. Wang was born in Inner Mongolia in 1973 and decided to use her scientific knowledge to conduct groundbreaking research instead of referencing unproven methods or mentioning distractions.
It appears that reducing the frequency of ovulation to once every three months might help women maintain healthy eggs for a more extended period and extend fertile years, postponing menopause.
Her research comes as China, like many Western democracies, encounters a steep decline in birth rates and an aging population, which threatens to undermine public health systems through reduced workforces and increased care costs. According to United Nations estimates, China’s population could halve by the end of the century if this trend continues.
Wang has two siblings — unthinkable for Chinese citizens born after 1979, when Communist leader Deng Xiaoping promoted the one-child policy devised by rocket specialist Song Jian.
China now faces the opposite problem. Despite allowing two children in 2015 and three in 2021, birth rates have failed to take off. Consequently, Wang’s Laboratory now looks into ways of prolonging reproductive periods.
Unlike the male body constantly produces sperms (up to 70 million spermatozoids in a single ejaculation), women are born with a fixed number of primordial follicles that are gradually depleted from puberty to menopause (only about 400 available eggs will be functional).
Chinese women display a noticeable fertility decline at ~ 37 years old, enter perimenopause at 46, and typically reach menopause at ~48.6 years old, as compared to 48.4 - 52 in Europe, 51.2 in Australia , 49.1 in Canada, and 51 in the USA.
In a 2024 Cell Discovery study by Long Yan et al., supervised by Wang, researchers looked into 28 ovaries from 26 Chinese women aged 35-52. The average number of primordial follicles per ovary dropped from 11,098 (ages 35-39) to 6,728 (ages 40-44), 1,019 (ages 45-49), and 151 (ages 50-52), accompanied by increased ovarian fibrosis. However, growing primary and secondary follicles were still present at age 49, suggesting that the remaining ~1,000 primordial follicles in perimenopausal ovaries could be activated to restore ovarian function.
By reducing menstrual cycles from roughly a dozen a year to four (once every three months), Wang hypothesizes that we might be able to keep healthy eggs, slow ovarian aging, and consequently delay menopause. Delaying menopause by even just a year, “would have huge social importance,” said the biologist in EL PAÍS.
Despite findings from mouse studies suggesting that it is possible to delay menopause, Wang warns that it is a double-edged sword, as suppressing ovulation also suppresses estrogen, putting one at risk of bone-density loss, osteoporosis, cardiovascular effects, and neurodegenerative diseases.
“When we stop ovulation, we save more eggs, but we also stop the body from making estrogen, and that molecule is absolutely vital for health,” Dr. Wang told EL PAÍS.
“If we inhibit ovulation, we can preserve available eggs, but at the same time, we inhibit the production of estrogen, which is a very important molecule for health,” Dr. Wang warned during the Spain conference.
Also Read: Study Reveals How Estrogen Exerts its Anti-Diabetic Effects
Ovaries are among the first organs to age, and Harvard University studies suggest ovarian aging influences broader aging. Dr. Nandita Palshetkar, Scientific Director and Head of the Bloom IVF Unit at Lilawati Hospital in Mumbai, noted in the India Today article that researchers are focused on “health span” — how long people stay healthy as they age.
“We all know the ovary is not only a reproductive organ, it is also an important endocrine organ producing oestrogen, progesterone and several molecules that influence bone health, cardiovascular function, brain health, cognition, metabolism, skin and overall well-being,” Dr. Palshetkar explained.
“Menstrual suppression alone does not necessarily preserve fertility or extend oestrogen production. It has not been proven for sure,” she added.
According to Wang, whose team patented and licensed the methods to a private company, stem cell transplants allowed four of 63 women with premature ovarian failure to have healthy children in a small clinical trial.
In the 2024 Cell Discovery study, researchers transplanted human embryonic stem cell-derived MSC-like cells (M cells) into naturally aging perimenopausal Cynomolgus monkeys aged 18-23 years (n = 7 treated, n = 3 saline control). M-cell transplantation increased ovarian diameters, endometrial thickness, and estradiol (E2) and progesterone (P4) levels.
After superovulation, treated monkeys yielded oocytes that fertilized via ICSI, whereas controls yielded none. Following natural mating, one treated monkey conceived and delivered a healthy baby monkey now over 3 years old — a breakthrough Wang discusses with pride.
Single-cell RNA sequencing and in vitro KGN cell assays showed that M cells improved follicular development and angiogenesis while reducing apoptosis, oxidative damage, inflammation, and fibrosis by upregulating PPARG, PRDX4, and RDX.
“There are studies showing that PRP injections into the ovary can help. Research is moving in many different directions,” Dr. Palshetkar said.
“I feel the future will be about rejuvenating the ovaries. And rejuvenation of the ovaries is not only for fertility, but has far-reaching implications for the overall health and healthy lifespan of women,” she added.
Also Read: What Happens to Ovaries After Menopause? Scientists Found a Surprising Second Job
Two weeks after fertilization, the embryo begins gastrulation to produce a three-dimensional body plan. Why half of all fertilizations fail may lie in this window, but most countries ban culturing human embryos beyond 14 days. Although China and other countries are preparing to update regulations to allow cultivation up to 20 or 28 days.
Wang is collaborating with Alfonso Martínez Arias at Pompeu Fabra University to build stem-cell embryonic models (organoids) to work around legal restrictions. Wang hopes to replicate the ovary, the embryo, and the placenta.
“Right before birth, the placenta holds around 58,000 cell nuclei and covers about 172 square feet. There’s no other organ-linked structure in the body that’s that big,” said Wang in a publication.
Public reaction to Wang’s work is mixed, and Wang admitted that her preliminary research — which steps outside the usual boundaries of science — may come too late to fix China’s demographic decline.
“It’s one thing to prove something possible in the lab, like slowing menstruation or making reproductive life longer. It is another thing entirely for people to actually want such things in practice,” said Wang in EL PAÍS.
Reference:
Yan, Long, Wan Tu, Xuehan Zhao, Haifeng Wan, Jiaqi Wu, Yuting Zhao, et al. “Stem Cell Transplantation Extends the Reproductive Life Span of Naturally Aging Cynomolgus Monkeys.” Cell Discovery 10, no. 1 (2024): 111.
https://pmc.ncbi.nlm.nih.gov/articles/PMC11535534/
(Rh/APC)
