Steroidogenic factor 1 (SF-1; Nr5a1) regulates the formation of the ovarian reserve

Camilla H.K. Hughes, Olivia E. Smith, Marie Charlotte Meinsohn, Mylène Brunelle, Nicolas Gévry, Bruce D. Murphy

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Abstract

The ovarian follicle reserve, formed pre- or perinatally, comprises all oocytes for lifetime reproduction. Depletion of this reserve results in infertility. Steroidogenic factor 1 (SF-1; Nr5a1) and liver receptor homolog 1 (LRH-1; Nr5a2) are two orphan nuclear receptors that regulate adult endocrine function, but their role in follicle formation is unknown. We developed models of conditional depletion of SF-1 or LRH-1 from prenatal ovaries. Depletion of SF-1, but not LRH-1, resulted in dramatically smaller ovaries and fewer primordial follicles. This was mediated by increased oocyte death, resulting from increased ovarian inflammation and increased Notch signaling. Major dysregulated genes were Iroquois homeobox 3 and 5 and their downstream targets involved in the establishment of the ovarian laminin matrix and oocyte-granulosa cell gap junctions. Disruptions of these pathways resulted in follicles with impaired basement membrane formation and compromised oocyte–granulosa communication networks, believed to render them more prone to atresia. This study identifies SF-1 as a key regulator of the formation of the ovarian reserve.

Original languageEnglish (US)
Article numbere2220849120
JournalProceedings of the National Academy of Sciences of the United States of America
Volume120
Issue number32
DOIs
StatePublished - Aug 8 2023

All Science Journal Classification (ASJC) codes

  • General

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