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J Appl Toxicol. 2019 Nov;39(11):1516-1531. doi: 10.1002/jat.3836. Epub 2019 Jul 23.

Developmental programming: Sex-specific programming of growth upon prenatal bisphenol A exposure.

Author information

1
College of Medicine, California Northstate University, Elk Grove, California.
2
Department of Animal Science, Michigan State University, East Lansing, Michigan.
3
Biostatistics Department, School of Public Health, Ann Arbor, Michigan.
4
Department of Pediatrics, University of Michigan, Ann Arbor, Michigan.
5
Department of Obstetrics and Gynecology and Wisconsin National Primate Research Center, University of Wisconsin, Madison, Wisconsin.
6
Department of Biostatistics, Pennington Biomedical Research Center, Baton Rouge, Louisiana.
7
New York State Department of Health, Wadsworth Center, Albany, New York.

Abstract

In both human and animals, in utero exposure to bisphenol A (BPA), an endocrine-disrupting chemical used in the production of plastics and epoxy resins, has been shown to affect offspring reproductive and metabolic health during adult life. We hypothesized that the effect of prenatal exposure to environmentally relevant doses of BPA will be evident during fetal organogenesis and fetal/postnatal growth trajectory. Pregnant ewes were administered BPA subcutaneously from 30 to 90 days of gestation (term 147 days). Fetal organ weight, anthropometric measures, maternal/fetal hormones and postnatal growth trajectory were measured in both sexes. Gestational BPA administration resulted in higher accumulation in male than female fetuses only at fetal day 65, with minimal impact on fetal/maternal steroid milieu in both sexes at both time points. BPA-treated male fetuses were heavier than BPA-treated female fetuses at fetal day 90 whereas this sex difference was not evident in the control group. At the organ level, liver weight was reduced in prenatal BPA-treated female fetuses, while heart and thyroid gland weights were increased in BPA-treated male fetuses relative to their sex-matched control groups. Prenatal BPA treatment also altered the postnatal growth trajectory in a sex-specific manner. Males grew slower during the early postnatal period and caught up later. Females, in contrast, demonstrated the opposite growth trend. Prenatal BPA-induced changes in fetal organ differentiation and early life growth strongly implicate translational relevance of in utero contributions to reproductive and metabolic defects previously reported in adult female offspring.

KEYWORDS:

developmental origins of health and disease; endocrine disruptors; obesity; obesogens

PMID:
31338854
PMCID:
PMC6810745
[Available on 2020-11-01]
DOI:
10.1002/jat.3836

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