Saturday, July 13, 2024

Deleting a MicroRNA Cluster Reversed Biological Sex in Mice

Transgender studies in mice? Just kidding!

"... In a recent study, researchers found that embryonic deletion of a cluster of microRNA—noncoding small molecules that control gene expression—transformed male mice into female mice. The findings ... revealed that non-coding molecules play a fundamental role in mammalian sex determination. ...
the team was surprised by the complete sex reversal. ...
Their finding was so rare that the team used several methods to confirm that XY mice developed a female phenotype. ..."

From the 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 involvement of non-coding regulation in this process remains unclear. Here we 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 delayed in XY knockout gonads, which develop 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."

Deleting a MicroRNA Cluster Reversed Biological Sex in Mice  | The Scientist Magazine® Removing microRNA that caused conversion of male mice embryos into female sheds light on key noncoding elements in sex determination.

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