As it is becoming increasingly accepted that maternal exposure to the ubiquitous environmental pollutant bisphenol A (BPA) predisposes offspring to metabolic impairments, paternal contribution in this context remains unresolved. To investigate a relationship between paternal BPA exposure and offspring obesity and glucose tolerance, a mouse model was developed using dietary BPA exposure at doses comparable to human exposure levels (7% Corn Oil diet (Control), 10 μg/mg/day (Lower BPA), and 10 mg/kg/day (Upper BPA)). Two exposure windows were investigated: 1) direct exposure of male mice beginning at sexual maturation (5 weeks of age) and continuing for 12 weeks prior to mating, and 2) in utero exposure, in which dams were exposed beginning 2 weeks prior to mating and ending at weaning. F1 males were sired to unexposed females. At 16 weeks of age, offspring from both exposure windows underwent body composition analysis via NMR or DEXA scan as well as glucose tolerance testing. Paternal BPA exposure during adulthood did not affect body weight, adiposity or glucose tolerance in offspring. In utero-exposed sires produced offspring that also had no changes in body weight or adiposity. However, female offspring from the Lower BPA dose were glucose intolerant. Females with glucose intolerance were selected for islet perifusion, and interestingly, those females from Lower BPA dose exhibited enhanced glucose-stimulated insulin secretion compared to controls indicating insulin resistance. These data demonstrate that while paternal BPA exposure after sexual maturity may be metabolically innocuous, paternal BPA exposure during gestation and lactation precipitates sex-specific impairments in glucose tolerance. Further studies are required to describe precisely the glucose homeostatic impairment and elucidate epigenetic changes in sperm associated with phenotypic transmission.


C.S. Rashid: None. A. Bansal: None. R.A. Simmons: None.

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