
TY  - JOUR
A1  - Dragovic, R. A. 
A1  - Ritter, L. J. 
A1  - Amato, F. 
A1  - Scott, S. J. 
A1  - Cranfield, M. 
A1  - Groome, N. P. 
A1  - Armstrong, D. T. 
A1  - Gilchrist, R. B. 
T1  - 251. Regulation of mouse cumulus expansion by oocyte-secreted growth differentiation factor-9 (GDF-9)
JF  - Reproduction, Fertility and Development
JO  - Reprod. Fertil. Dev.
Y1  - 2004
VL  - 16
IS  - 9
SP  - 251
EP  - 251
KW  - 
UR  - https://doi.org/10.1071/SRB04ABS251 
N2  - Oocyte paracrine signalling is necessary for mouse cumulus cell expansion, an important preovulatory process. The oocyte-secreted factor growth differentiation factor-9 (GDF-9) signals through the bone morphogenetic protein receptor-II (BMPR-II) and is currently the primary candidate molecule for the cumulus expansion enabling factor (CEEF). The present study was conducted to determine whether in the mouse GDF-9 is the CEEF. Cumulus oocyte complexes (COC) were collected from eCG-primed mice and the oocyte was microsurgically removed to generate an oocytectomised complex (OOX). An established scoring system was used to measure FSH-induced cumulus expansion&#x003B; 0 (no expansion) to +4 (maximum expansion). OOX complexes treated with FSH alone failed to expand (score: 0), whereas expansion was significantly (P &#60; 0.05) induced by either recombinant mouse GDF-9 (score&#x003B; mean +/&#8211; SEM: 2.7 +/&#8211; 0.1), recombinant TGF-&#956;1 (score: 2.6 +/&#8211; 0.2) or co-culture with oocytes (score: 2.3 +/&#8211; 0.2). A GDF-9 neutralising antibody mAb-53, raised against hGDF-9, was effective in neutralising the response of OOX complexes to GDF-9 (score: 0.1 +/&#8211; 0.1), but had no significant effect on the expansion of OOX complexes co-cultured with oocytes (score: 2.3 +/&#8211; 0.2). Likewise, a TGF-&#956; antagonist neutralised (P &#60; 0.05) TGF-&#956;-induced, but not oocyte-induced, expansion of OOX complexes. A soluble portion of the BMPR-II ectodomain, a known GDF-9 antagonist, failed to neutralise oocyte-induced cumulus expansion (P &#62; 0.05) at the highest dose implying that BMPR-II is not a critical receptor involved in regulating cumulus expansion. Using real-time RT-PCR, hyaluronan synthase-2 (HAS2) mRNA expression by OOXs was upregulated 6- to 7-fold by oocytes and GDF-9. The GDF-9 neutralising antibody mAb-53, partially neutralised GDF-9-induced OOX HAS2 expression, but not oocyte-induced HAS2 expression. This study provides evidence that like TGF-&#956;1, GDF-9 can enable FSH-induced cumulus expansion, however more importantly demonstrates that neither GDF-9 nor TGF-&#956;1 alone account for the crucial oocyte-secreted factor regulating cumulus expansion in the mouse. 
ER  -

