Boston - Researchers have discovered a gene mutation in mice that causes premature ovarian failure, a form of infertility affecting an estimated 250 000 women in the United States.
The investigators at Dana-Farber Cancer Institute and Brigham and Women's Hospital (BWH) say the discovery will lead to unique animal models of premature ovarian failure (POF), or early menopause, useful for further studying the poorly understood condition.
POF, which is diagnosed in 1 in 100 women ages 30 to 39, results from the depletion of a woman's supply of eggs early in her reproductive years.
The lead author of the report is Diego H. Castrillon, MD, PhD, a postdoctoral fellow in the laboratory of Ronald A. DePinho, MD, at Dana-Farber, where the work was done. DePinho is the senior author, and three other Dana-Farber researchers contributed to the paper.
Continues Below ↓
Castrillon made the comparison to an hourglass The findings grew out of an experiment in which the researchers created mice lacking both copies of the FOXO3a gene, which belongs to the forkhead gene family.
As transcription regulators, or switches that turn other genes on and off, forkhead genes are believed to control processes related to aging, cancer and diabetes. In this experiment, the researchers "knocked out" the FOXO3a gene, effectively mutating it, in mice to observe the consequences.
As the gene-altered mice aged, the females were observed to have fewer and smaller litters, and by 15 weeks of age - comparable to early adulthood in a woman - they were sterile.
Further study revealed that within the ovaries of mice lacking the FOXO3a gene, the follicles that contain eggs had been activated earlier and much more widely than in the females with normal FOXO3a genes.
When a follicle is activated, it moves from the "resting pool" - a female's entire repository of eggs - to the "growing pool" and begins maturation, a process that is necessary before the egg can be released (ovulation) prior to fertilisation.
Once activated, a follicle has a finite lifespan, however, so the premature activation of follicles resulted in the early death of most eggs in mice that lacked the FOXO3a gene.
Castrillon made the comparison to an hourglass: "There is a finite number of grains of sand that are released in a metred way. Similarly, a woman's eggs are gradually released over her reproductive lifespan.
Menopause occurs when all the grains of sand have fallen. In mice lacking the FOXO3a gene, all of the grains of sand fall out very quickly, resulting in early menopause. "Our findings raise the possibility that increased activation of eggs over a woman's lifespan could result in premature ovarian failure and early menopause."
From the experimental results, it appears that abnormal FOXO3a gene function leads to faulty regulation of follicle activation, causing POF in mice.
Continues...
» View article on a single page
|
StumbleUpon
Reddit
Digg
Delicious
Newsvine
Facebook
muti
Twitter
