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Mol Cell Endocrinol

Title:		Social and neuromolecular phenotypes are programmed by prenatal exposures to endocrine-disrupting chemicals
Author(s):		Topper VY; Reilly MP; Wagner LM; Thompson LM; Gillette R; Crews D; Gore AC;
Address:		"The Institute for Cellular and Molecular Biology, The University of Texas at Austin, Austin, TX 78712, USA. Division of Pharmacology and Toxicology, The University of Texas at Austin, Austin, TX 78712, USA. The Institute for Cellular and Molecular Biology, The University of Texas at Austin, Austin, TX 78712, USA; Department of Integrative Biology, The University of Texas at Austin, Austin, TX 78712, USA. The Institute for Cellular and Molecular Biology, The University of Texas at Austin, Austin, TX 78712, USA; Division of Pharmacology and Toxicology, The University of Texas at Austin, Austin, TX 78712, USA. Electronic address: andrea.gore@austin.utexas.edu"
Journal Title:		Mol Cell Endocrinol
Year:		2019
Volume:		20181001
Issue:
Page Number:		133 - 146
DOI:		10.1016/j.mce.2018.09.010
ISSN/ISBN:		1872-8057 (Electronic) 0303-7207 (Print) 0303-7207 (Linking)
Abstract:		"Exposures to endocrine-disrupting chemicals (EDCs) affect the development of hormone-sensitive neural circuits, the proper organization of which are necessary for the manifestation of appropriate adult social and sexual behaviors. We examined whether prenatal exposure to polychlorinated biphenyls (PCBs), a family of ubiquitous industrial contaminants detectable in virtually all humans and wildlife, caused changes in sexually-dimorphic social interactions and communications, and profiled the underlying neuromolecular phenotype. Rats were treated with a PCB commercial mixture, Aroclor 1221 (A1221), estradiol benzoate (EB) as a positive control for estrogenic effects of A1221, or the vehicle (4% DMSO), on embryonic day (E) 16 and 18. In adult F1 offspring, we first conducted tests of ultrasonic vocalization (USV) calls in a sociosexual context as a measure of motivated communications. Numbers of certain USV call types were significantly increased by prenatal treatment with A1221 in males, and decreased by EB in females. In a test of sociosexual preference for a hormone-vs. a non-hormone-primed opposite sex conspecific, male (but not female) nose-touching with opposite-sex rats was significantly diminished by EDCs. Gene expression profiling was conducted in two brain regions that are part of the social decision-making network in the brain: the medial preoptic nucleus (MPN) and the ventromedial nucleus (VMN). In both regions, many more genes were affected by A1221 or EB in females than males. In female MPN, A1221 changed expression of steroid hormone receptor and neuropeptide genes (e.g., Ar, Esr1, Esr2, and Kiss1). In male MPN, only Per2 was affected by A1221. The VMN had a number of genes affected by EB compared to vehicle (females: Kiss1, Kiss1r, Pgr; males: Crh) but not A1221. These differences between EB and A1221 indicate that the mechanism of action of A1221 goes beyond estrogenic pathways. These data show sex-specific effects of prenatal PCBs on adult behaviors and the neuromolecular phenotype"
Keywords:		"Animals Corticosterone/blood Endocrine Disruptors/*toxicity Female Gene Expression Regulation Male Mating Preference, Animal Phenotype Pregnancy Prenatal Exposure Delayed Effects/*genetics/*pathology Preoptic Area/metabolism Rats, Sprague-Dawley Sex Chara;"
Notes:		"MedlineTopper, Viktoria Y Reilly, Michael P Wagner, Lauren M Thompson, Lindsay M Gillette, Ross Crews, David Gore, Andrea C eng R01 ES020662/ES/NIEHS NIH HHS/ R01 ES023254/ES/NIEHS NIH HHS/ Research Support, N.I.H., Extramural Ireland 2018/10/06 Mol Cell Endocrinol. 2019 Jan 5; 479:133-146. doi: 10.1016/j.mce.2018.09.010. Epub 2018 Oct 1"