Fibrillin-3 in the fetal ovary: can it contribute to polycystic ovary syndrome?

Evaluation of: Hatzirodos N, Bayne RA, Irving-Rodgers HF et al. Linkage of regulators of TGF-b activity in the fetal ovary to polycystic ovary syndrome. FASEB J. 25(7), 2256-2265 (2011). Polycystic ovary syndrome (PCOS), a prevalent hyperandrogenic and anovulatory infertility and metabolic syndrome in reproductive-aged women, is heritable but its etiology is unknown. An allele within an intron of fibrillin-3, a TGF-beta pathway regulator, is reliably associated with PCOS, and the epigenome of an early gestation monkey model for PCOS implicates altered TGF-beta signaling. In the recent article by Hatzirodos et al., and in contrast to prior findings in mature human ovaries, prominent and transient fibrillin-3 expression is found in human and bovine fetal ovarian stroma during early gestation. Such developmentally constrained ovarian expression of a gene associated with PCOS phenotype has considerable implications for fetal origins of PCOS in women. Further study is needed, however, to determine whether differential expression of fetal ovarian fibrillin-3 results in polycystic ovary morphology, and whether differential fetal expression of fibrillin-3 in non-ovarian tissues enables PCOS-like dysfunction.