ESPE Abstracts (2021) 94 WG4.1

ESPE2021 Working Group Symposia ESPE Working Group on Disorders of Sex Development (DSD) Symposium (2 abstracts)

New insights into sex differentiation and their relevance to disorders of sex development

Barbara Nicol


Embryos initially form undifferentiated gonads, reproductive tracts and external genitalia that will progressively acquire female or male characteristics. This fate decision is initiated in the undifferentiated gonads and depends on sex chromosomes and fine-tuned expression of complex networks of molecular pathways. Defects at different levels of this cascade of events can trigger a large spectrum of Disorders of sex development (DSDs), defined as “congenital conditions within which the development of chromosomal, gonadal, and anatomic sex is atypical”. For a majority of DSD cases, the genetic etiology remains unfortunately unknown. Our lab uses the mouse as a model to understand the molecular events that control sex differentiation during fetal development. Supporting cells dictate the fate of the gonads by differentiating into either Sertoli cells or granulosa cells. We recently identified the transcription factor RUNX1 as a supporting cell marker that becomes granulosa cell specific during gonad differentiation. RUNX1 plays complementary/redundant roles with FOXL2 to maintain fetal granulosa cell identity and combined loss of RUNX1 and FOXL2 results in masculinization of fetal ovaries. Genome-wide binding of RUNX1 overlaps with FOXL2 occupancy in the fetal ovary, suggesting that RUNX1 and FOXL2 directly target common sets of genes. This result also highlights the interest of identifying the genomic regions bound by transcription factors involved in gonad differentiation as potential regions of interest for DSDs, beyond the genes themselves. Finally, new technologies like single-cell RNA-seq are revolutionizing the field by creating a detailed roadmap of dynamic changes happening in each cell population composing the reproductive organs, which could be a steppingstone in better understanding of the molecular origins of DSDs.

Volume 94

59th Annual ESPE (ESPE 2021 Online)

22 Sep 2021 - 26 Sep 2021

European Society for Paediatric Endocrinology 

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