PMID- 31501865 OWN - NLM STAT- MEDLINE DCOM- 20200821 LR - 20201201 IS - 1096-0929 (Electronic) IS - 1096-6080 (Print) IS - 1096-0929 (Linking) VI - 172 IP - 2 DP - 2019 Dec 1 TI - Gestational Exposure to Bisphenol A and Bisphenol S Leads to Fetal Skeletal Muscle Hypertrophy Independent of Sex. PG - 292-302 LID - 10.1093/toxsci/kfz198 [doi] AB - Gestational exposure to bisphenol A (BPA) can lead to offspring insulin resistance. However, despite the role that the skeletal muscle plays in glucose homeostasis, it remains unknown whether gestational exposure to BPA, or its analog bisphenol S (BPS), impairs skeletal muscle development. We hypothesized that gestational exposure to BPA or BPS will impair fetal muscle development and lead to muscle-specific insulin resistance. To test this, pregnant sheep (n = 7-8/group) were exposed to BPA or BPS from gestational day (GD) 30 to 100. At GD120, fetal skeletal muscle was harvested to evaluate fiber size, fiber type, and gene and protein expression related to myogenesis, fiber size, fiber type, and inflammation. Fetal primary myoblasts were isolated to evaluate proliferation and differentiation. In fetal skeletal muscle, myofibers were larger in BPA and BPS groups in both females and males. BPA females had higher MYH1 (reflective of type-IIX fast glycolytic fibers), whereas BPS females had higher MYH2 and MYH7, and higher myogenic regulatory factors (Myf5, MyoG, MyoD, and MRF4) mRNA expression. No differences were observed in males. Myoblast proliferation was not altered in gestationally BPA- or BPS-exposed myoblasts, but upon differentiation, area and diameter of myotubes were larger independent of sex. Females had larger myofibers and myotubes than males in all treatment groups. In conclusion, gestational exposure to BPA or BPS does not result in insulin resistance in fetal myoblasts but leads to fetal fiber hypertrophy in skeletal muscle independent of sex and alters fiber type distribution in a sex-specific manner. CI - (c) The Author(s) 2019. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com. FAU - Jing, Jiongjie AU - Jing J AD - Department of Animal Science, Michigan State University, East Lansing, Michigan 48824. FAU - Pu, Yong AU - Pu Y AD - Department of Animal Science, Michigan State University, East Lansing, Michigan 48824. FAU - Gingrich, Jeremy AU - Gingrich J AD - Department of Animal Science, Michigan State University, East Lansing, Michigan 48824. AD - Department of Pharmacology and Toxicology, Michigan State University, East Lansing, Michigan 48824. FAU - Veiga-Lopez, Almudena AU - Veiga-Lopez A AD - Department of Animal Science, Michigan State University, East Lansing, Michigan 48824. LA - eng GR - K22 ES026208/ES/NIEHS NIH HHS/United States GR - R01 ES027863/ES/NIEHS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. PL - United States TA - Toxicol Sci JT - Toxicological sciences : an official journal of the Society of Toxicology JID - 9805461 RN - 0 (Benzhydryl Compounds) RN - 0 (Endocrine Disruptors) RN - 0 (Phenols) RN - 0 (Sulfones) RN - 80-09-1 (bis(4-hydroxyphenyl)sulfone) RN - MLT3645I99 (bisphenol A) SB - IM MH - Animals MH - Benzhydryl Compounds/blood/*toxicity MH - Cell Differentiation/drug effects MH - Cell Proliferation/drug effects MH - Cells, Cultured MH - Endocrine Disruptors/blood/*toxicity MH - Female MH - Fetal Development/*drug effects MH - Gestational Age MH - Hypertrophy MH - Muscle Cells/drug effects/pathology MH - Muscle Development/*drug effects MH - Muscle, Skeletal/*drug effects/embryology/pathology MH - Myoblasts/drug effects/pathology MH - Phenols/blood/*toxicity MH - Pregnancy MH - Prenatal Exposure Delayed Effects/*chemically induced/pathology MH - Primary Cell Culture MH - Sheep MH - Sulfones/blood/*toxicity PMC - PMC6876539 OTO - NOTNLM OT - bisphenols OT - fetal OT - myogenesis OT - skeletal muscle EDAT- 2019/09/11 06:00 MHDA- 2020/08/22 06:00 PMCR- 2020/12/01 CRDT- 2019/09/11 06:00 PHST- 2019/09/11 06:00 [pubmed] PHST- 2020/08/22 06:00 [medline] PHST- 2019/09/11 06:00 [entrez] PHST- 2020/12/01 00:00 [pmc-release] AID - 5566505 [pii] AID - kfz198 [pii] AID - 10.1093/toxsci/kfz198 [doi] PST - ppublish SO - Toxicol Sci. 2019 Dec 1;172(2):292-302. doi: 10.1093/toxsci/kfz198.