Follicle-stimulating hormone regulates oocyte growth by modulation of expression of oocyte and granulosa cell factors

Endocrinology. 2005 Feb;146(2):941-9. doi: 10.1210/en.2004-0826. Epub 2004 Nov 11.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Morphogenetic Protein 15
  • Cell Division / drug effects
  • Cell Division / physiology
  • Cells, Cultured
  • Female
  • Follicle Stimulating Hormone / pharmacology*
  • Gene Expression / drug effects
  • Growth Differentiation Factor 9
  • Intercellular Signaling Peptides and Proteins / genetics
  • Mice
  • Mice, Mutant Strains
  • Oncogene Proteins / genetics
  • Oocytes / cytology*
  • Oocytes / drug effects
  • Oocytes / physiology*
  • Proto-Oncogene Proteins c-kit
  • RNA, Messenger / analysis
  • Stem Cell Factor / genetics

Substances

  • Bmp15 protein, mouse
  • Bone Morphogenetic Protein 15
  • Gdf9 protein, mouse
  • Growth Differentiation Factor 9
  • Intercellular Signaling Peptides and Proteins
  • Oncogene Proteins
  • RNA, Messenger
  • Stem Cell Factor
  • Follicle Stimulating Hormone
  • Proto-Oncogene Proteins c-kit