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Ovary gene may explain certain aspects of infertility

Boston--December 2, 2002--Harvard Medical School researchers have uncovered an ovary gene whose absence from mouse egg cells produced severe pregnancy complications. The gene, Fmn2, which produces the protein formin-2, is similar in mice and humans and offers promise for understanding embryo loss, birth defects, and infertility in women. The study appears in the December Nature Cell Biology.

"As humans we are incredibly bad at producing eggs with the normal number of chromosomes, which is the leading cause of pregnancy loss in women," says Benjamin Leader, an HMS MD/PhD candidate, and the paper's lead author. "The biological means for ensuring proper distribution of chromosomes to the egg has been difficult to determine.

"Our study shows that the formin-2 gene is required in order to ensure the proper distribution of chromosomes to the egg. About one percent of women suffer from recurrent pregnancy loss, which can be defined as a loss of greater than two or three pregnancies. We are now actively searching for mutations involving the formin-2 gene in women with reproductive loss and infertility," Leader added.

Egg cells lacking Fmn2 were unable to complete the first round of reproductive cell division, known as meiosis I. The egg cell failed to correctly position a significant protein-DNA, the metaphase spindle, thereby halting the division process. The result was lack of formation of the first polar body, a new cell that signifies completion of the first meiotic division, and the daughter egg cell, which would otherwise develop into a mature egg.

Leader observed that Fmn2-deficient female mice produced embryos with three or five sets of chromosomes, a deviation that resulted in cell death. Normal mice with Fmn2 produce embryos with two sets of chromosomes. The researchers also found that healthy ovaries transplanted into Fmn2-deficient females rescued pregnancy loss, whereas transplant of Fmn2-deficient ovaries into healthy females destr
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Contact: Donna Burtanger
donna_burtanger@hms.harvard.edu
617-432-0442
Harvard Medical School
25-Nov-2002


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