Meiotic maturation of incompetent prepubertal sheep oocytes is induced by paracrine factor(s) released by gonadotropin-stimulated oocyte-cumulus cell complexes and involves mitogen-activated protein kinase activation

Endocrinology. 2008 Jan;149(1):100-7. doi: 10.1210/en.2007-0874. Epub 2007 Sep 20.

Abstract

In this study, sheep oocyte-cumulus cell complexes (OCC) derived from medium (M) antral follicles (M-OCC) were in vitro matured alone or in coculture with OCC derived from small (S) antral follicles (S-OCC) to investigate the contribution of cumulus cells (CC) and oocytes to the process of oocyte meiotic maturation and cumulus expansion (CE). Experiments were conducted with or without gonadotropins (FSH/LH). Regardless of culture conditions, about 12% of S-oocytes reached the metaphase II stage, and S-CC showed a low degree of CE. In contrast, both maturational processes were significantly stimulated by gonadotropins in M-OCC. However, about 48% of S-oocytes progressed to metaphase II, and S-CC expanded after coculture with gonadotropin-stimulated M-OCC and M-CC but not with mural granulosa cells. Both maturational processes were inhibited when S-OCC were cocultured with M-denuded oocytes, or when S-denuded oocytes were cocultured with M-CC. The capacity of these paracrine factor(s) to activate the MAPK pathway in somatic and germ cells of S-complexes was investigated. It was found that MAPK kinase/MAPK phosphorylation levels in M-OCC but not in S-OCC were significantly increased by gonadotropins, first in CC and later in the oocytes. Kinase phosphorylations were activated only in S-oocytes cocultured with M-OCC or M-CC. These results demonstrate that soluble factors specifically produced by M-CC are capable to induce meiotic maturation and CE in S-complexes by acting via CC. These factors can induce MAPK activation only in S-oocytes, whose meiotic arrest could be due to the inability of surrounding CC to respond to gonadotropin stimulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / drug effects
  • Cell Differentiation / physiology
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Coculture Techniques
  • Cumulus Cells / drug effects*
  • Cumulus Cells / physiology
  • Enzyme Activation / physiology
  • Female
  • Gonadotropins / pharmacology*
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Intercellular Signaling Peptides and Proteins / pharmacology*
  • MAP Kinase Kinase Kinases / metabolism
  • Meiosis / drug effects*
  • Meiosis / physiology
  • Mitogen-Activated Protein Kinases / metabolism*
  • Models, Biological
  • Oocytes / drug effects*
  • Oocytes / physiology
  • Oogenesis / drug effects*
  • Oogenesis / physiology
  • Sheep

Substances

  • Gonadotropins
  • Intercellular Signaling Peptides and Proteins
  • Mitogen-Activated Protein Kinases
  • MAP Kinase Kinase Kinases