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Updated: Nov 11, 2025

Enrichment of Mammalian Tissues and Xenopus Oocytes with Cholesterol
Published on: March 25, 2020
Cholesterol Contributes to Male Sex Differentiation Through Its Developmental Role in Androgen Synthesis and Hedgehog
Anbarasi Kothandapani1, Colin R Jefcoate2, Joan S Jorgensen1
1Department of Comparative Biosciences, University of Wisconsin-Madison, Madison, Wisconsin 53705, USA.
Abstract:
Two specialized functions of cholesterol during fetal development include serving as a precursor to androgen synthesis and supporting hedgehog (HH) signaling activity. Androgens are produced by the testes to facilitate masculinization of the fetus. Recent evidence shows that intricate interactions between the HH and androgen signaling pathways are required for optimal male sex differentiation and defects of either can cause birth anomalies indicative of 46,XY male variations of sex development (VSD). Further, perturbations in cholesterol synthesis can cause developmental defects, including VSD, that phenocopy those caused by disrupted androgen or HH signaling, highlighting the functional role of cholesterol in promoting male sex differentiation. In this review, we focus on the role of cholesterol in systemic androgen and local HH signaling events during fetal masculinization and their collective contributions to pediatric VSD.
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