4.7 Article

Obesity modulates cell-cell interactions during ovarian folliculogenesis

期刊

ISCIENCE
卷 25, 期 1, 页码 -

出版社

CELL PRESS
DOI: 10.1016/j.isci.2021.103627

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资金

  1. Ministry of Science and Technology of China [2018YFC1003401, 2018YFA0107701]
  2. National Natural Science Foundation of China [31771590, 31822035]
  3. CAS Project for Young Scientists in Basic Research [YSBR-012]
  4. Strategic Collaborative Research Program of the Ferring Institute of Reproductive Medicine, Ferring Pharmaceuticals
  5. Chinese Academy of Sciences [FIRMC200510]

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Obesity affects female reproduction by disrupting the balance of ovarian follicle cell types. This study reveals that excessive androgen secretion from endocrine theca cells contributes to this imbalance through interactions with granulosa cells. The use of an androgen receptor antagonist can alleviate this imbalance. Additionally, specific markers for evaluating female fertility in obesity were identified.
Obesity is known to affect female reproduction, as evidenced by obese patients suffering from subfertility and abnormal oogenesis. However, the underlying mechanisms by which obesity impairs folliculogenesis are poorly documented. Here, we performed comprehensive single-cell transcriptome analysis in both regular diet (RD) and obese mouse models to systematically uncover how obesity affects ovarian follicle cells and their interactions. We found an increased proportion of Inhbb highly expressed granulosa cells (GCs) among all the GC subpopulations in obese mice. Under obese conditions, excessive androgen secreted from endocrine theca cells (ETCs) may contribute to the imbalanced change of GCsubtypes through ETCs-GCs interactions. This is alleviated by enzalutamide, an androgen receptor antagonist. We also identified and confirmed typical GC markers, such as Marcks and Prkar2b, for sensitive evaluation of female fertility in obesity. These data represent a resource for studying transcriptional networks and cell-cell interactions during folliculogenesis under physiological and pathological conditions.

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