Bisphenol A alters differentiation of Leydig cells in the rabbit fetal testis

• Published in: The International journal of developmental biology Vol. 65; no. 4-5-6; pp. 403 - 412
• Main Authors: Ortega-García, Alexis P, Díaz-Hernández, Verónica, Collazo-Saldaña, Pedro, Merchant-Larios, Horacio
• Format: Journal Article
• Language: English
• Published: Spain University of the Basque Country Press 2021
• Subjects: Androgen receptors; Androgens; Animals; Benzhydryl Compounds - pharmacology; Bisphenol A; Cell differentiation; Cell Differentiation - drug effects; Cell proliferation; Differentiation; Electron microscopy; Female; Gene expression; Genes; Gestation; Gonads; Leydig cells; Leydig Cells - cytology; Leydig Cells - drug effects; Male; Maternal Exposure; Medulla oblongata; Organs; Paracrine signalling; Phenols - pharmacology; Phenotypes; Placenta; Pregnancy; Rabbits; Signaling; Testes; Testis - cytology; Testis - drug effects; Testosterone
• ISSN: 0214-6282; 1696-3547
• DOI: 10.1387/ijdb.200185hm

The endocrine disruptor Bisphenol A (BPA) crosses the placental barrier and reaches the fetal organs, including the gonads. In the testis, fetal Leydig cells (FLC) produce testosterone required for the male phenotype and homeostatic cell-cell signaling in the developing testis. Although it is known that BPA affects cell proliferation and differentiation in FLC, results concerning the mechanism involved are contradictory, mainly due to differences among species. Fast developing fetal gonads of rodents lack cortex and medulla, whereas species with more extended gestation periods form these two tissue compartments. The rabbit provides a good subject for studying the disruptive effect of BPA in fetal Leydig and possible postnatal endocrine consequences in adult Leydig cells. Here, we investigated the impact of BPA administered to pregnant rabbits on the FLC population of the developing testes. Using qRT-PCR, we assessed the levels of S , , and androgen receptor genes, and levels of fetal serum testosterone were measured by ELISA. These levels correlated with both the mitotic activity and the ultrastructural differentiation of the FLC by confocal and electron microscopy, respectively. Results indicate that BPA alters the expression levels of essential genes involved in androgen paracrine signaling, modifies the proliferation and differentiation of the FLCs, and alters the levels of serum testosterone after birth. Thus, BPA may change the postnatal levels of serum testosterone due to the impaired FLC population formed by the proliferating stem and non-proliferating cytodifferentiated FLC.