Editors' ChoiceObesity

It’s Not My Fault, I Was Born This Way

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Science Translational Medicine  24 Feb 2010:
Vol. 2, Issue 20, pp. ec28
DOI: 10.1126/scitranslmed.3000981

“It’s not my fault, I was born this way.” How often have people said this in response to questions about their metabolism? Well, to some extent they may be right. Developmental programming and the effect of the intrauterine environment on fetal health are now hot topics in the lay and scientific press, particularly with regard to how they relate to the obesity epidemic and reproduction.

Previous work with animal models suggests that prenatal exposure to testosterone plays a role in the development of polycystic ovary syndrome (PCOS), a leading cause of infertility. For example, exposure of ewes to excess testosterone during a critical period of prenatal development culminates in lack of ovulation, excessive secretion of androgens, a surplus of luteinizing hormone, and polyfollicular ovaries in female offspring, all of which are features comparable with those in PCOS in women. Padmanabhan et al. have now investigated the effect of prenatal exposure to testosterone on insulin sensitivity—a key factor in type 2 diabetes—and found that such exposure led to reduced insulin sensitivity in the offspring. This characteristic is found in more than 70% of PCOS women and in all individuals with type 2 diabetes. In addition, postnatal weight gain increased the severity of the reproductive and metabolic defects, and the offspring of overweight controls manifested defects in insulin dynamics, supporting the idea that obesity-related traits can be transferred to the next generation.

Other studies indicate that these findings in sheep may be applicable to humans and support the role of prenatal steroids—particularly androgens—in fetal metabolic programming and reproductive health. The results of Padmanabhan et al. illustrate the importance of postnatal nutrition and weight gain on the phenotypic expression of these traits.

V. Padmanabhan et al., Developmental programming: Impact of prenatal testosterone excess and postnatal weight gain on insulin sensitivity index and transfer of traits to offspring of overweight females. Endocrinology 151, 595–605 (2010). [Abstract]

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