Endocrine Abstracts

Fetal programming is triggered when a stimulus or insult occurs at a stage in fetal life, critical for target organ differentiation, growth and development. As a result, permanent changes in organ structure or function are induced that manifest as disease in adulthood. Impaired fetal growth or stress during fetal life and subsequent cardiometabolic disease in adult life is a well recognized example of fetal programming.

Growing evidence suggests that prenatal exposure to excess androgens may be another source of fetal programming leading to alterations to the adult female phenotype resembling those of polycystic ovary syndrome (PCOS). Experimental studies have shown that female primates, exposed in utero to androgen excess, exhibit in adult life the phenotypic features of PCOS, including enlarged polyfollicular, hyperandrogenic, anovulatory ovaries with accompanying LH hypersecretion, central adiposity, and impaired insulin secretion and action. Clinical observations also suggest a potential fetal origin of PCOS. Women with fetal androgen excess disorders, including congenital 21-hydroxylase deficiency and congenital adrenal virilizing tumors, develop features characteristic of PCOS during adulthood despite the normalization of androgen excess after birth.

In regard to PCOS in humans, the potential origin of increased androgenic activity during fetal life is not clear. However, maternal and/or fetal hyperandrogenism may provide a plausible mechanism for programming of PCOS and this, in part, may be genetically determined. Genetic association studies have indicated that common polymorphic variants of genes determining androgen activity, or genes that influence the availability of androgens to target tissues, are associated with PCOS and increased androgen levels. These genetic variants may provide the genetic link to the developmental origin hypothesis of PCOS.

In conclusion, prenatal androgenization of the female fetus induced by genetic and/or environmental factors or the interaction of both, may programme differentiating target tissues towards the development of PCOS phenotype in adult life.