Study provides new insights into development of ovarian follicles and previously unknown variations microbiologystudy

A recent study published in Nature Communications by researchers at Karolinska Institutet offers new insights into the development of ovarian follicles, which are vital for female fertility as they contain oocytes.

The study, led by Pauliina Damdimopoulou, Senior Lecturer and Research Group Leader at the Department of Clinical Science, Intervention and Technology, provides a detailed comparison of immature follicles from both children and adults. The findings reveal significant previously unknown variations in immature oocytes and identify key markers involved in the early growth activation of follicles.

Ovarian follicles are essential for female fertility, forming during fetal development and establishing a finite reserve of approximately one million primordial follicles. Each follicle contains one immature oocyte that is arrested in development and stays dormant until it is activated to grow. The activation and growth of follicles to ovulation is a process that spans about a year in humans.

While full growth to ovulation is only possible after puberty, the early stages of growth occur even in children. This study focuses on the early arrested follicles and their first stages of growth, providing the first ever comparison between adult and child follicles.

The research team analyzed the transcriptomes of 120 immature follicles from both children and adults. They discovered two main types of follicles in both age groups: one with a gene expression profile typical of immature oocytes, and another with very low oocyte markers but a predicted role in signaling. This suggests that a subset of follicles may not be focused on maturing their oocytes but instead may play a role in secreting growth factors, potentially supporting the growth of other follicles.

While transcriptional changes during early follicle growth were similar overall in both children and adults, variations related to the extracellular matrix, theca cells, and miRNA profiles were observed. This suggests that the immature follicles formed during fetal development undergo changes as girls reach sexual maturity.

The study also found that follicle morphology alone is insufficient for reliably categorizing follicles, highlighting the need for additional markers. The identification of marker genes for follicle subtypes and early growth could help refine methods for fertility assessment in women.

Implications for fertility preservation

Children and women undergoing cancer treatments are at a higher risk of infertility because chemotherapy is toxic to follicles. Some of the samples in the study were derived from children undergoing fertility preservation, a technique in which a piece of an ovary containing immature follicles is removed and cryopreserved before the damaging treatments begin.

The authors found that follicles from treated children displayed increased inflammation. It is not known how inflammation in follicles might impact the quality of oocytes.

“Ovarian tissue cryopreservation is an established method to preserve fertility in adults and is even applied in prepuberty despite unproven efficacy,” says Pauliina Damdimopoulou. “Our findings will help refine these techniques and improve outcomes for patients across different age groups.”

The research underscores the importance of understanding the complex biology of ovarian follicles in both children and adults to develop better fertility preservation strategies as well as infertility treatments. By identifying key markers for ovarian follicle health, the study paves the way for more effective interventions to protect and preserve fertility.

“Our study provides a deeper understanding of the heterogeneity in ovarian follicles and emphasizes the need for more precise markers for follicle classification,” adds Damdimopoulou. “This knowledge is crucial for advancing fertility preservation methods and could even impact how we assess fertility in adult women seeking medically assisted reproduction”