CBX2 and the Ovary: Novel Insights into Regulatory Networks in Humans

Abstract

Leila Bouazzi, Mariangela Franco, Alexander Maret and Anna Biason-Lauber

Background: Chromobox protein homolog 2 (CBX2) is a DNA-interacting protein present in humans in two isoforms, CBX2.1 and CBX2.2. Isoform-1 promotes testis development, butthe role of both variants in the female gonad pathway remains unknown.

Methods: To understand its function in human ovaries, we evaluated expression of known female genes i.e.FOXL2, RSPO1 and WNT4 in human pre-granulosa cells after forced expression and RNA interference of CBX2 isoforms and vice versa.

Results: The two isoforms appeared to be functionally distinct. CBX2.1 has proved to be a pro-male by enhancing SOX9, SF1 and androgen receptor (AR) expression, whereas CBX2.2 might be partly pro-female most likely via interaction with RSPO1 and the regulation of ovary developmental markers (i.e. OCT-4, AMH and ERβ).

Conclusions: Both CBX2 isoforms might act as distinct regulatory agents protecting granulosa cells from uncontrolled growth and proliferation by adjusting WNT4 and RSPO1 signaling pathways, and participate to follicular development and fate by regulating the expression of SF1 and AR, thus potentially influencing fertility, menopause, ovarian cancer and perhaps polycystic ovary syndrome.

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