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Title: The aryl hydrocarbon receptor mediates sex ratio distortion in the embryos sired by TCDD-exposed male mice.

Authors: Bircsak, Kristin M; Copes, Latresa T; King, Sara; Prantner, Andrew M; Hwang, Wei-Ting; Gerton, George L

Published In Reprod Toxicol, (2020 06)

Abstract: Many reports describe an association between preconceptional paternal exposure to environmental chemicals, including the persistent organic pollutant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) with an increased number of female offspring. We chronically treated wild-type C57BL/6 male mice with TCDD to investigate a role for the aryl hydrocarbon receptor (AHR) transcription factor. These mice had a 14 % lower male:female sex ratio than control mice, which was not observed in TCDD-treated Ahr knock out mice. AHR target genes Cyp1a1 and Ahrr were upregulated in the liver and testis of WT mice and Ahr expression was higher in the epididymis (2-fold) and liver (18-fold) than in whole testis tissue. The AHR protein was localized to round spermatids, elongating spermatids, and Leydig cells in the testis of WT mice. These studies demonstrate AHR involvement in the sex ratio distortion of TCDD-exposed males and the need for evaluating the molecular and genetic mechanism of this process.

PubMed ID: 32335222 Exiting the NIEHS site

MeSH Terms: Animals; Basic Helix-Loop-Helix Transcription Factors/genetics; Basic Helix-Loop-Helix Transcription Factors/metabolism*; Embryo, Mammalian/drug effects; Environmental Pollutants/toxicity*; Epididymis/drug effects; Epididymis/metabolism; Female; Liver/drug effects; Liver/metabolism; Male; Mice, Inbred C57BL; Mice, Knockout; Polychlorinated Dibenzodioxins/toxicity*; Receptors, Aryl Hydrocarbon/genetics; Receptors, Aryl Hydrocarbon/metabolism*; Sex Ratio*; Spermatids/drug effects; Testis/cytology; Testis/drug effects; Testis/metabolism

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