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

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.

• Authors: Benjamin Leader, Hyunjung Lim, Mary Jo Carabatsos, Anne Harrington, Jeffrey Ecsedy, David Pellman, Richard Maas, Philip Leder
• Journal: Nature cell biology (Nat Cell Biol) Vol. 4 Issue 12 Pg. 921-8 (Dec 2002) ISSN: 1465-7392 [Print] England
• PMID: 12447394 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Nerve Tissue Proteins

Topics

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