Abstract : The formation of functional eggs in the ovarian follicles is a critical process of early mammalian development. While genetic studies have revealed key genes for oocyte functions, the underlying mechanisms driving follicle growth remain enigmatic. Recent studies showed that follicle growth is sensitive to mechanical environment, calling for a need to understand mechanical signalling within follicle. Here, we investigate the mechanical functions of theca cells (TCs), which sit on a basement membrane encapsulating the follicles. Using live imaging and ex vivo reconstitution, we demonstrate that the TCs are highly contractile and generate compressive stress to modulate follicle growth. We further found that the TCs are mechanosensitive to stretch and substrate stiffness, suggesting that the basement membrane may in turn regulate TC functions in vivo. We hypothesise that such mechanical feedback is essential for regulating follicle growth and oocyte functions through mechanotransduction pathways. Our work has implications for future understanding and treatment of ovarian disease and infertility.

Biography: Trained in soft matter physics, Joe carried out his PhD research with Jochen Guck at the University of Cambridge, studying the mechanical and optical properties of cells and nuclei using novel biophotonic tools. He then joined the lab of Takashi Hiiragi (EMBL Heidelberg) to study the roles of fluid pressure in regulating mouse blastocyst size and cell fate specification during early embryo development (Chan, 2019, Nature). Currently at NUS, his lab focuses on understanding how mechano-chemical signalling regulate mammalian ovarian follicle growth during development and ageing. To address these questions, the lab combines unique ex vivo reconstitution with quantitative imaging, biophysical, molecular and computational approaches to map out intra-follicular cellular dynamics and mechanical interactions. Other research themes in his lab include the biophysical control of ovulation and the study of crosstalk between ovarian macrophages and ECM in contributing to inflammation and fibrosis during ageing. He has recently been awarded the Singaporean Teaching and Academic Research Talent Inauguration Award (2022).