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Toxicol Sci

Title:		"Distinct Transcriptional Profiles of the Female, Male, and Finasteride-Induced Feminized Male Anogenital Region in Rat Fetuses"
Author(s):		Schwartz CL; Vinggaard AM; Christiansen S; Darde TA; Chalmel F; Svingen T;
Address:		"Division of Diet, Disease Prevention and Toxicology, National Food Institute, Technical University of Denmark, Kgs. Lyngby, Denmark. INSERM, Universite de Rennes, EHESP, IRSET (Institut de Recherche en Sante, Environnement et Travail) - UMR_S1085, Rennes, France"
Journal Title:		Toxicol Sci
Year:		2019
Volume:		169
Issue:		1
Page Number:		303 - 311
DOI:		10.1093/toxsci/kfz046
ISSN/ISBN:		1096-0929 (Electronic) 1096-0929 (Linking)
Abstract:		"A short anogenital distance (AGD) in males is a marker for incomplete masculinization and a predictor of adverse effects on male reproductive health. For this reason, AGD is used to assess the endocrine disrupting potential of chemicals for risk assessment purposes. The molecular mechanisms underpinning this chemically induced shortening of the AGD, however, remains unclear. Although it is clear that androgen receptor-mediated signaling is essential, evidence also suggest the involvement of other signaling pathways. This study presents the first global transcriptional profile of the anogenital tissue in male rat fetuses with chemically induced short AGD, also including comparison to normal male and female control animals. The antiandrogenic drug finasteride (10 mg/kg bw/day) was used to induce short AGD by exposing time-mated Sprague Dawley rats at gestation days 7-21. The AGD was 37% shorter in exposed male fetuses compared with control males at gestation day 21. Transcriptomics analysis on anogenital tissues revealed a sexually dimorphic transcriptional profile. More than 350 genes were found to be differentially expressed between the 3 groups. The expression pattern of 4 genes of particular interest (Esr1, Padi2, Wnt2, and Sfrp4) was also tested by RT-qPCR analyses, indicating that estrogen and Wnt2 signaling play a role in the sexually dimorphic development of the anogenital region. Our transcriptomics profiles provide a stepping-stone for future studies aimed at characterizing the molecular events governing development of the anogenital tissues, as well as describing the detailed Adverse Outcome Pathways for short AGD; an accepted biomarker of endocrine effects for chemical risk assessment"
Keywords:		Anal Canal/*drug effects/embryology Androgen Antagonists/*toxicity Animals Endocrine Disruptors/*toxicity Estrogen Receptor alpha/genetics/metabolism Female Feminization/*chemically induced/embryology/genetics Fetal Development Finasteride/*toxicity Gene;
Notes:		"MedlineSchwartz, Camilla Lindgren Vinggaard, Anne Marie Christiansen, Sofie Darde, Thomas Alain Chalmel, Frederic Svingen, Terje eng Research Support, Non-U.S. Gov't 2019/02/16 Toxicol Sci. 2019 May 1; 169(1):303-311. doi: 10.1093/toxsci/kfz046"