Formin-2, polyploidy, hypofertility and positioning of the meiotic spindle in mouse oocytes

Nat Cell Biol. 2002 Dec;4(12):921-8. doi: 10.1038/ncb880.

Abstract

Successful reproduction in mammals requires a competent egg, which is formed during meiosis through two assymetrical cell divisions. Here, we show that a recently identified formin homology (FH) gene, formin-2 (Fmn2), is a maternal-effect gene that is expressed in oocytes and is required for progression through metaphase of meiosis I. Fmn2(-/-) oocytes cannot correctly position the metaphase spindle during meiosis I and form the first polar body. We demonstrate that Fmn2 is required for microtubule-independent chromatin positioning during metaphase I. Fertilization of Fmn2(-/-) oocytes results in polyploid embryo formation, recurrent pregnancy loss and sub-fertility in Fmn2(-/-) females. Injection of Fmn2 mRNA into Fmn2-deficient oocytes rescues the metaphase I block. Given that errors in meiotic maturation result in severe birth defects and are the most common cause of chromosomal aneuploidy and pregnancy loss in humans, studies of Fmn2 may provide a better understanding of infertility and birth defects.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / genetics
  • Female
  • Fertility / genetics
  • Gene Expression Regulation, Developmental / physiology
  • Meiosis / genetics*
  • Meiosis / physiology
  • Mice
  • Nerve Tissue Proteins / genetics*
  • Nerve Tissue Proteins / physiology
  • Oocytes / cytology
  • Oocytes / physiology*
  • Polyploidy

Substances

  • Nerve Tissue Proteins