Classification of Atretic Small Antral Follicles in the Human Ovary

Author:

Wei Fu1,Fan Xueying1ORCID,del Valle Julieta S.1ORCID,Asseler Joyce D.234,van der Meeren Lotte E.56ORCID,Cheng Hui1ORCID,Roelen Bernard A. J.7ORCID,Louwe Leoni A.8,Pilgram Gonneke S. K.8,van der Westerlaken Lucette A. J.8,van Mello Norah M.234,Chuva de Sousa Lopes Susana M.19ORCID

Affiliation:

1. Department of Anatomy and Embryology, Leiden University Medical Center, 2333 ZC Leiden, The Netherlands

2. Department of Obstetrics and Gynaecology, Amsterdam University Medical Center, 1105 AZ Amsterdam, The Netherlands

3. Amsterdam UMC, Centre of Expertise on Gender Dysphoria, 1081 HV Amsterdam, The Netherlands

4. Amsterdam Reproduction and Development Research Institute, 1081 HV Amsterdam, The Netherlands

5. Department of Pathology, Leiden University Medical Center, 2333 ZC Leiden, The Netherlands

6. Department of Pathology, Erasmus Medical Center, 3015 GD Rotterdam, The Netherlands

7. Anatomy and Physiology, Department Clinical Sciences, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 1, 3584 CL Utrecht, The Netherlands

8. Department of Gynaecology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands

9. Department for Reproductive Medicine, Ghent University Hospital, 9000 Ghent, Belgium

Abstract

The reproductive lifespan in humans is regulated by a delicate cyclical balance between follicular recruitment and atresia in the ovary. The majority of the small antral follicles present in the ovary are progressively lost through atresia without reaching dominance, but this process remains largely underexplored. In our study, we investigated the characteristics of atretic small antral follicles and proposed a classification system based on molecular changes observed in granulosa cells, theca cells, and extracellular matrix deposition. Our findings revealed that atresia spreads in the follicle with wave-like dynamics, initiating away from the cumulus granulosa cells. We also observed an enrichment of CD68+ macrophages in the antrum during the progression of follicular atresia. This work not only provides criteria for classifying three stages of follicular atresia in small antral follicles in the human ovary but also serves as a foundation for understanding follicular degeneration and ultimately preventing or treating premature ovarian failure. Understanding follicular remodeling in the ovary could provide a means to increase the number of usable follicles and delay the depletion of the follicular reserve, increasing the reproductive lifespan.

Funder

European Research Council

Novo Nordisk Foundation

China Scholarship Council

Publisher

MDPI AG

Subject

Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis

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