Maternal age dependent loss of SMC1 transcripts in human oocytes. V. Jobanputra1, S. K. Nurudeen2, M. Shirazi1, R. W. Prosser2, A. Naini1, J. K. Kline3, M. V. Sauer2, D. Warburton1,4 1) Pathology; 2) Obstetrics and Gynecology; 3) Epidemiology; 4) Genetics and Development, Columbia University, New York, NY.

   The pathogenic mechanisms underlying the well-established association of advancing maternal age with increased risk of meiotic nondisjunction are unknown. Studies of human oocytes obtained in assisted reproductive settings suggest that premature chromatid separation may be more common than previously thought. One hypothesis is that age-related meiotic errors are the result of failure of cohesins to maintain the association of chromatids during either the resting period in female meiosis or the completion of MI or MII. Evidence supporting this hypothesis is based mainly on studies in the mouse showing that cohesion binding to chromosomes decreases in oocytes of older mothers and that mutations in cohesins lead to errors in meiosis. We set out to examine this hypothesis in humans by measuring the transcript levels of SMC1B, one of the meiosis-specific cohesins, in human oocytes. Immature oocytes which were not used for intracytoplasmic sperm injection ICSI were collected from women undergoing in vitro fertilization (IVF). A total of 90 oocytes were collected from 67 women (age range 21 to 43 years). We extracted RNA from the oocytes and used quantitative real-time PCR to measure the relative amount of SMC1 mRNA. We classified women in four age groups: < 30years (n=27), 30-34 years (n=26), 35-39 years (n=23) and > 40 years (n=14). SMC1 transcripts were detectable in all oocytes. Maternal age was negatively associated with SMC1 mRNA levels. When comparing the transcript levels by age groups, women over 40 years of age had significantly lower SMC1 transcript levels compared with women < 30 years (p=0.0234). Our results implicate an age-dependent loss in the transcript levels of SMC1 in human oocytes. To our knowledge, this is the first study to demonstrate a relation between maternal age and cohesion level in human oocytes.

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