This illustration shows a cross-section of the ovary of a rhesus macaque, with female reproductive cells highlighted in green. The small dots around the periphery (there are 25–30 of them in this plane) represent the ovarian reserve. The large cell is located inside the antral follicle, which synthesizes enzymes for hormonal production. (Image credit: Sissi Wamaita)
Researchers have come closer to deciphering the mechanisms by which the ovaries form a lifelong supply of eggs, known as the ovarian reserve.
The work, published August 26 in Nature Communications, details the emergence and evolution of the cellular structures and biomolecules involved in creating ovarian reserve in primates, from the embryonic stages of ovarian development to six months of age.
“This model helps fill in gaps in fundamental questions in biology,” Amander Clark, a co-author of the study and a developmental biology expert at UCLA, told Live Science.
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As Clark noted, the created model will allow the development of improved laboratory analogues of ovaries for the study of reproductive pathologies, including PCOS – a hormonal disorder that can provoke infertility.
Mysterious development
As a key reproductive organ, the ovaries perform two functions: the production of eggs and the synthesis of sex hormones (estrogen, progesterone, testosterone).
Their development begins in the embryo at about the sixth week. Primordial germ cells unite into complex nested structures, which later disintegrate into individual oocytes. The latter are surrounded by pregranulosa cells, which regulate maturation.
The aggregate of oocytes with the pregranulosa layer forms primordial follicles, the basis of the ovarian reserve.
These structures are formed by the 20th week of embryogenesis, concentrating on the periphery of the ovary. The most centrally located follicles are activated first, triggering growth and hormonal secretion.
According to Clark, it is the primordial follicles that provide the reproductive and endocrine functions of the organ.
Many pathologies, including PCOS, are associated with dysfunction of these structures. However, the mechanisms of their formation remain poorly understood.
Detailing the stages of ovarian reserve creation in the prenatal period can explain the causes of late fertility disorders. “This was the goal of our study,” the scientist explained.
Unexpected results
To study the process in primates, the team chose a species that is physiologically close to humans. This allowed them to extrapolate the data to the human body.
Scientists collected samples of ovarian tissue from monkey embryos and fetuses at different stages: day 34 (sexual differentiation), day 41 (beginning of ovarian growth), day 50–52 (end of embryogenesis), day 100 (nest expansion), and day 130 (follicle formation) after conception.
Analysis of the spatial arrangement and molecular profiles of cells revealed key events in the formation of the reserve.
It turned out that pregranulosa cells are formed in two waves, and only the second (41–52 days) participates in the formation of primordial follicles.
Two genes were also found to be activated before the second wave. Further study of these genes may shed light on the origins of reserve development disorders.
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Particularly surprising was the fact that some follicles were activated before birth. As the authors suggested, this discovery may help in understanding the causes of PCOS.
Luz Garcia-Alonso of the Wellcome Sanger Institute, who was not involved in the work, told Live Science that the researchers were dealing with highly dynamic cellular changes during the embryonic period. More frequent sampling time points are needed to get a full picture, she said.
Disclaimer
The material is intended for informational purposes and does not replace medical advice.
Sophie Berdugo, Social Link Navigator, Live Science Contributor
Sophie is a UK science journalist covering a range of topics from primatology to cosmology. Her work has appeared in New Scientist, The Observer and BBC Wildlife. In 2025, her work was nominated for an ASBJ award. Before her career in journalism, she completed a PhD in evolutionary anthropology at Oxford, studying tool use in chimpanzees.
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