Follicle-stimulating hormone regulates oocyte growth by modulation of expression of oocyte and granulosa cell factors.
Oocyte-granulosa cell communication is essential for oocyte development. The aims of this study were: 1) to determine the effect of FSH on expression of Kit ligand (KL), growth/differentiation factor-9, bone morphogenetic protein (BMP)-15, and Kit during growth of oocyte-granulosa cell complexes (OGCs) in vitro; 2) to investigate the role of BMP-15 in regulation of KL expression; and 3) to correlate mRNA expression with oocyte growth. OGCs from 12-d-old mice were cultured for up to 7 d in the presence of FSH [0.05 ng/ml (low), 5 ng/ml (high)] or BMP-15 (10 or 100 ng/ml). Transcripts were quantified using real-time RT-PCR, and oocyte and OGC diameters were measured. FSH regulated KL expression in a biphasic manner, with low FSH decreasing the KL-1/KL-2 ratio, and high FSH increasing the KL-1/KL-2 ratio, compared with controls (P < 0.05). The decrease in KL-1/KL-2 ratio with low FSH was due to increased KL-2 mRNA expression. Both FSH concentrations increased OGC diameter (P < 0.05), but only low FSH promoted oocyte growth (P < 0.05). High FSH also decreased BMP-15 expression (P < 0.05). FSH-stimulated oocyte growth was inhibited by Gleevec, an inhibitor of Kit activity. BMP-15 increased both KL-1 and KL-2 mRNA levels in a dose-dependent manner (P < 0.05) but did not alter the KL-1/KL-2 ratio or promote oocyte growth. When the KL-1/KL-2 ratio was increased by exogenous KL-1, FSH-stimulated oocyte growth was suppressed (P < 0.05), suggesting that lowered KL-1/KL-2 ratio is important for oocyte growth. In summary, the correct concentration of FSH is crucial for appropriate modulation of KL and BMP-15 to promote oocyte growth.
Thomas
Fiona H
FH
Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa Regional Cancer Centre, Ottawa, Ontario, Canada K1H 1C4. fthomas@uottawa.ca.
Ethier
Jean-François
JF
Shimasaki
Shunichi
S
Vanderhyden
Barbara C
BC
D000818:Animals; D055430:Bone Morphogenetic Protein 15; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D005260:Female; D005640:Follicle Stimulating Hormone / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D055429:Growth Differentiation Factor 9; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics; D051379:Mice; D008817:Mice, Mutant Strains; D015513:Oncogene Proteins / Q000235:genetics; D009865:Oocytes / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D019009:Proto-Oncogene Proteins c-kit; D012333:RNA, Messenger / Q000032:analysis; D019089:Stem Cell Factor / Q000235:genetics
C525902:Bmp15 protein, mouse; D055430:Bone Morphogenetic Protein 15; C525898:Gdf9 protein, mouse; D055429:Growth Differentiation Factor 9; D036341:Intercellular Signaling Peptides and Proteins; D015513:Oncogene Proteins; D012333:RNA, Messenger; D019089:Stem Cell Factor; D005640:Follicle Stimulating Hormone; D019009:Proto-Oncogene Proteins c-kit