期刊
TOXICOLOGICAL SCIENCES
卷 172, 期 2, 页码 292-302出版社
OXFORD UNIV PRESS
DOI: 10.1093/toxsci/kfz198
关键词
bisphenols; fetal; skeletal muscle; myogenesis
类别
资金
- National Institute of Environmental Health Sciences of the National Institute of Health [1K22ES026208, R01ES027863]
- Michigan State University (MSU) General Funds
- AgBioResearch
- United States Department of Agriculture (USDA) National Institute of Food and Agriculture
- China Scholarship Council Fellowship
- MSU Office of the Vice President for Research and Graduate Studies
- MSU College of Graduate Studies
- MSU College of Human Medicine
- MSU AgBioResearch
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.
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