Targeted disruption of Mapk14 (p38MAPKalpha) in granulosa cells and cumulus cells causes cell-specific changes in gene expression profiles that rescue COC expansion and maintain fertility.

Journal Article (Journal Article)

MAPK14 (p38MAPKalpha) is critical for FSH and prostaglandin E (PGE)2 signaling cascades in granulosa cells (GCs) and cumulus cell-oocyte complexes (COCs) in culture, indicating that this kinase might impact follicular development and COC expansion in vivo. Because Mapk14 knockout mice are embryonic lethal, we generated GC specific Mapk14 knockout mice (Mapk14gc(-/-)) by mating Mapk14(fl/fl) and Cyp19-Cre mice. Unexpectedly, the Mapk14gc(-/-) female mice were fertile. Analyses of gene expression patterns showed that amphiregulin (Areg) and epiregulin (Ereg), two key regulators of ovulation and COC expansion, were up-regulated in the GCs but down-regulated in cumulus cells of the mutant mice in vivo. COCs from the mutant mice expanded and expressed matrix-related genes, if cultured with AREG, but not when cultured with forskolin or PGE2, the latter being a key factor regulating MAPK14 activity in cumulus cells. Conversely, when GCs from the Mapk14gc(-/-) mice were cultured with forskolin, they produced more Areg and Ereg mRNA than did wild-type GCs. These results indicate that disruption of Mapk14 selectively alters the expression of Areg and other genes in each cell type. Greater AREG and EREG produced by the GCs appears to by-pass and compensate for the critical need for MAPK14 signaling and induction of Areg/Ereg (and hence matrix genes) by PGE2 in cumulus cells of the mutant mice. In conclusion, although MAPK14 is not overtly essential for preovulatory follicle development or events associated with ovulation and luteinization in vivo, it does impact gene expression profiles.

Full Text

Duke Authors

Cited Authors

  • Liu, Z; Fan, H-Y; Wang, Y; Richards, JS

Published Date

  • September 2010

Published In

Volume / Issue

  • 24 / 9

Start / End Page

  • 1794 - 1804

PubMed ID

  • 20610537

Pubmed Central ID

  • PMC2940481

Electronic International Standard Serial Number (EISSN)

  • 1944-9917

Digital Object Identifier (DOI)

  • 10.1210/me.2010-0086

Language

  • eng

Conference Location

  • United States