Estrogen promotes the development of mouse cumulus cells in coordination with oocyte-derived GDF9 and BMP15.
The differentiation and function of cumulus cells depend upon oocyte-derived paracrine factors, but studies on the estrogen receptor knockout mice suggested that estrogen also participates in these processes. This study investigates the possible coordination of estrogen and oocytes in the development and function of cumulus cells using cumulus expansion and the expression of transcripts required for expansion as functional endpoints. Preantral granulosa cell-oocyte complexes developed in vitro with 17β-estradiol (E2) exhibited increased levels of cumulus expansion and Has2 transcripts, encoding hyaluronan synthase 2, compared with those developed without E2. Moreover, cumulus cell-oocyte complexes (COCs) isolated from antral follicles and maintained in culture without E2 exhibited reduced cumulus expansion and Has2 mRNA levels compared with freshly isolated COCs. Exogenous E2, provided during the maintenance culture, alleviated these deficiencies. However, when oocytes were removed from COCs, E2 supplementation did not maintain competence to undergo expansion; the presence in culture of either fully grown oocytes or recombinant growth differentiation factor 9 (GDF9) was required. Recombinant bone morphogenetic protein 15, but not fibroblast growth factor 8, augmented the GDF9 effect. Oocytes or GDF9 suppressed cumulus cell levels of Nrip1 transcripts encoding nuclear receptor-interacting protein 1, a potential inhibitor of estrogen receptor signals. Therefore, E2 and oocyte-derived paracrine factors GDF9 and bone morphogenetic protein 15 coordinate to promote the development of cumulus cells and maintain their competence to undergo expansion. Furthermore, suppression of Nrip1 expression in cumulus cells by oocyte may be one mechanism mediating cross talk between oocyte and E2 signals that promotes follicular development.
The Jackson Laboratory, Bar Harbor, Maine 04609, USA.
Koji
K
Sugiura
You-Qiang
YQ
Su
Qinglei
Q
Li
Karen
K
Wigglesworth
Martin M
MM
Matzuk
John J
JJ
Eppig
D048868:Adaptor Proteins, Signal Transducing / Q000037:antagonists & inhibitors / Q000235:genetics; D000818:Animals; D055430:Bone Morphogenetic Protein 15 / Q000378:metabolism*; D002097:C-Reactive Protein / Q000235:genetics; D015815:Cell Adhesion Molecules / Q000235:genetics; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D054885:Cumulus Cells / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D051546:Cyclooxygenase 2 / Q000235:genetics; D004958:Estradiol / Q000494:pharmacology*; D004967:Estrogens / Q000502:physiology; D005260:Female; D051524:Fibroblast Growth Factor 8 / Q000378:metabolism; D014453:Glucuronosyltransferase / Q000235:genetics / Q000378:metabolism; D055429:Growth Differentiation Factor 9 / Q000378:metabolism*; D006801:Humans; D000076002:Hyaluronan Synthases; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000235:genetics; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors / Q000235:genetics; D000078723:Nuclear Receptor Interacting Protein 1; D009865:Oocytes / Q000187:drug effects* / Q000378:metabolism; D011960:Receptors, Estrogen / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D000099153:Pentraxins
D048868:Adaptor Proteins, Signal Transducing; D055430:Bone Morphogenetic Protein 15; D002097:C-Reactive Protein; D015815:Cell Adhesion Molecules; D051546:Cyclooxygenase 2; D004958:Estradiol; D004967:Estrogens; D051524:Fibroblast Growth Factor 8; D014453:Glucuronosyltransferase; D055429:Growth Differentiation Factor 9; D000076002:Hyaluronan Synthases; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D000078723:Nuclear Receptor Interacting Protein 1; D011960:Receptors, Estrogen; D000099153:Pentraxins; C525902:Bmp15 protein, mouse; C496457:Fgf8 protein, mouse; C525898:Gdf9 protein, mouse; C000627127:NRIP1 protein, human; C000627128:Nrip1 protein, mouse; C513057:Tnfaip6 protein, mouse; C077623:Ptgs2 protein, mouse; C491099:Has2 protein, mouse