Surface mechanics and compressive stress impact mammalian follicle development

Arikta Biswas, Yuting Lou, Boon Heng Ng, Kosei Tomida, Sukhada Darpe, Kim Whye Leong, Zihao Wu, Thong Beng Lu, Xiang Teng, Yusuke Toyama, Isabelle Bonne and Chii Jou Chan ()
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Arikta Biswas: National University of Singapore
Yuting Lou: National University of Singapore
Boon Heng Ng: National University of Singapore
Kosei Tomida: National University of Singapore
Sukhada Darpe: National University of Singapore
Kim Whye Leong: National University of Singapore
Zihao Wu: National University of Singapore
Thong Beng Lu: National University of Singapore
Xiang Teng: National University of Singapore
Yusuke Toyama: National University of Singapore
Isabelle Bonne: National University of Singapore
Chii Jou Chan: National University of Singapore

Nature Communications, 2025, vol. 16, issue 1, 1-19

Abstract: Abstract The maturation of functional eggs in ovaries is essential for successful reproduction in mammals. Despite its biological and clinical importance, the underlying mechanisms regulating folliculogenesis remain enigmatic. Here, using murine ovaries, we report that the theca cells surrounding secondary follicles play a critical role in regulating follicle development through mechanical signalling. Using biophysical approaches, we found that the contractile theca cells exert significant compressive stress to the follicular interior through active assembly of fibronectin. Manipulation of compressive stress by targeting theca cell contractility, basement membrane integrity or intrafollicular pressure leads to changes in follicle size and mechanics, granulosa cell YAP signalling and oocyte-granulosa cell communications. Transcriptomics and quantitative immunofluorescence reveal that compressive stress impacts functional follicle growth through regulating the balance between granulosa cell proliferation and death that drives tissue pressure homeostasis. Altogether, our study uncovers unique mechanical functions of theca cells and provides quantitative evidence of the role of compressive stress in regulating mammalian folliculogenesis.

Date: 2025
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DOI: 10.1038/s41467-025-65390-y

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