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

Abstract

Evaluation of: Hatzirodos N, Bayne RA, Irving-Rodgers HF et al. Linkage of regulators of TGF-β 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-β pathway regulator, is reliably associated with PCOS, and the epigenome of an early gestation monkey model for PCOS implicates altered TGF-β 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.

Keywords::

• developmental programming
• extracellular matrix
• ovarian stroma remodeling
• TGF-β

Financial & competing interests disclosure

The author is a consultant for, and receives research funding from, Viamet Pharmaceuticals (NC, USA) and receives research funding from the NIH (grant RR000167). The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.