Reproductive Research

By Riva Preil

It is well known that a defective BRCA-1 gene has been associated with increased risk of developing breast cancer.  However, scientists under the auspices of the National Institutes of Health have recently discovered an additional clinical feature connected to this gene: age-related fertility decline.

The ovaries of newborn baby girls contain approximately one million primordial follicle oocytes, immature egg cells.  When she reaches puberty, these eggs mature into viable, fertile egg cells which are released from each ovary once per month on an alternating basis.  Over the course of her reproductive life, most women only release approximately 500 of the one million eggs.  As a woman enters her mid to late thirties, the number and health of her eggs significantly decreases.  In fact, by the time she arrives at her early fifties, the large quantity of original eggs has disappeared.  Most of the original oocytes self-destruct due to an accumulation of double stranded DNA breaks.  Earlier in life, individuals have improved ability to “autocorrect” breaks in DNA molecules due to properly functioning repair molecules.  However, as a woman ages, her supply of repair molecules decreases, which contributes to an accumulation of double-stranded breaks.

BRCA-1, along with ATM, Rad51, and MRE11, are DMA repair genes- they are responsible for producing repair molecules. A dysfunctional BRCA-1 gene, therefore, can be likened to a spell check system that has gone awry- it is less capable of detecting DNA problems that require fixing.  Therefore, a dysfunctional BRCA-1 gene is associated with faster decline in reproductive abilities compared to women with fully functioning ovarian DNA molecule repair systems.  This knowledge can help guide future research involving searching for methods to improve the DNA repair system. By fixing the broken spell check system, so to speak, ovarian aging may be slowed down and perhaps fertility can be prolonged.  The direct benefit that this will have to many couples is extremely valuable.

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