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GCNF‐dependent repression of BMP‐15 and GDF‐9 mediates gamete regulation of female fertility
Author(s) -
Lan ZiJian,
Gu Peili,
Xu Xueping,
Jackson Kathy J.,
DeMayo Francesco J.,
O'Malley Bert W.,
Cooney Austin J.
Publication year - 2003
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/cdg405
Subject(s) - biology
To determine the function of germ cell nuclear factor ( GCNF ) in female reproduction, we generated an oocyte‐specific GCNF knockout mouse model ( GCNF fl/fl Zp3 Cre + ). These mice displayed hypofertility due to prolonged diestrus phase of the estrous cycle and aberrant steroidogenesis. These reproductive defects were secondary to a primary defect in the oocytes, in which expression of the paracrine transforming growth factor‐β signaling molecules, bone morphogenetic protein 15 ( BMP‐15 ) and growth differentiation factor 9 ( GDF‐9 ), were up‐regulated in GCNF fl/fl Zp3 Cre + females at diestrus. This was a direct effect of GCNF, as molecular studies showed that GCNF bound to DR0 elements within the BMP‐15 and GDF‐9 gene promoters and repressed their reporter activities. Consistent with these findings, abnormal double‐oocyte follicles, indicative of aberrant BMP‐15/GDF‐9 expression, were observed in GCNF fl/fl Zp3 Cre + females. The Cre/loxP knockout of GCNF in the oocyte has uncovered a new regulatory pathway in ovarian function. Our results show that GCNF directly regulates paracrine communication between the oocyte and somatic cells by regulating the expression of BMP‐15 and GDF‐9 , to affect female fertility.