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Complete male-to-female sex reversal in XY mice lacking the miR-17~92 cluster

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Item Type:Article
Title:Complete male-to-female sex reversal in XY mice lacking the miR-17~92 cluster
Creators Name:Hurtado, A. and Mota-Gómez, I. and Lao, M. and Real, F.M. and Jedamzick, J. and Burgos, M. and Lupiáñez, D.G. and Jiménez, R. and Barrionuevo, F.J.
Abstract:Mammalian sex determination is controlled by antagonistic gene cascades operating in embryonic undifferentiated gonads. The expression of the Y-linked gene SRY is sufficient to trigger the testicular pathway, whereas its absence in XX embryos leads to ovarian differentiation. Yet, the potential involvementofnon-codingregulationinthisprocessremainsunclear.Herewe show that the deletion of a single microRNA cluster, miR-17~92,induces complete primary male-to-female sex reversal in XY mice. Sry expression is delayedinXYknockoutgonads,whichdevelop as ovaries. Sertoli cell differentiation is reduced, delayed and unable to sustain testicular development. Pre-supporting cells in mutant gonads undergo a transient state of sex ambiguity which is subsequently resolved towards the ovarian fate. The miR-17~92 predicted target genes are upregulated, affecting the fine regulation of gene networks controlling gonad development. Thus, microRNAs emerge as key components for mammalian sex determination, controlling Sry expression timing and Sertoli cell differentiation.
Keywords:Cell Differentiation, Developmental Gene Expression Regulation, Disorders of Sex Development, Gonads, Knockout Mice, MicroRNAs, Ovary, Sertoli Cells, Sex Determination Processes, Sex Differentiation, Sex-Determining Region Y Protein, Testis, Animals, Mice
Source:Nature Communications
Publisher:Nature Publishing Group
Page Range:3809
Date:7 May 2024
Official Publication:https://doi.org/10.1038/s41467-024-47658-x
PubMed:View item in PubMed

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