Open AccessCBX2 and the Ovary: Novel Insights into Regulatory Networks in Humans
Publication year - 2018
Publication title -
journal of gynecology and reproductive medicine
Language(s) - English
Resource type - Journals
ISSN - 2576-2842
DOI - 10.33140/jgrm/02/01/00002
Subject(s) - wnt4 , biology , gene isoform , microbiology and biotechnology , polycystic ovary , ovary , genetics , signal transduction , gene , endocrinology , wnt signaling pathway , insulin resistance , insulin
Background: Chromobox protein homolog 2 (CBX2) is a DNA-interacting protein present in humans in twoisoforms, CBX2.1 and CBX2.2. Isoform-1 promotes testis development, butthe role of both variants in the femalegonad 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 isoformsand vice versa.Results: The two isoforms appeared to be functionally distinct. CBX2.1 has proved to be a pro-male by enhancingSOX9, SF1 and androgen receptor (AR) expression, whereas CBX2.2 might be partly pro-female most likely viainteraction 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 fromuncontrolled growth and proliferation by adjusting WNT4 and RSPO1 signaling pathways, and participate tofollicular development and fate by regulating the expression of SF1 and AR, thus potentially influencing fertility,menopause, ovarian cancer and perhaps polycystic ovary syndrome.