Spatiotemporally primed coelomic epithelium and supporting-like cells establish the dual origin of granulosa cells.

Authors

Cyril Djari, Chloé Mayère, Maëva Guy, Aitana Perea-Gomez, Laura Bellutti, Paul Barreau, Herta Ademi, Agathe Rozier, Anthony S Martinez, Tyler J Gibson, Françoise Kühne, Cassandre Guérin, Dagmar Wilhelm, Gabriel Livera, Jennifer McKey, Marie-Christine Chaboissier, Serge Nef

Published in

Proceedings of the National Academy of Sciences of the United States of America. Volume 123. Issue 40. Pages e2615939123. Oct 06, 2026. Epub Sep 28, 2026.

Abstract

Ovarian organogenesis relies on the coordinated specification of supporting and steroidogenic lineages from multipotent progenitors of the coelomic epithelium. However, how these progenitors adopt distinct fates and differentiate into pregranulosa cells and steroidogenic progenitors of theca cells remain poorly understood. Here, we show that the dynamics of ovarian somatic lineage specification are conserved between human and mouse. Coelomic epithelial cells covering the fetal ovaries are heterogeneous and already biased toward supporting or steroidogenic fates. This priming is spatially and temporally organized, influenced by proximity to the mesonephros, and characterized by a transient coexistence of both progenitor types before resolving into predominantly supporting-biased cells. In mice, local delamination of these primed epithelial progenitors seeds intragonadal domains that give rise to pregranulosa and steroidogenic progenitors. We further demonstrate that these fetal steroidogenic progenitors generate adult stromal and theca cells. In addition, we uncover that granulosa cells arise from two distinct sources: Coelomic epithelium-derived progenitors generate the majority of cortical granulosa cells forming the long-lived follicle reserve, whereas supporting-like cells contribute to a smaller granulosa subpopulation. Together, these findings establish a revised model of ovarian development in which early spatial patterning of coelomic epithelial progenitors directs lineage specification, reveals the dual origin of granulosa cells, and defines the developmental origin of theca cells.

PMID:
42804628
Bibliographic data and abstract were imported from PubMed on 29 Sep 2026.

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