MATERNAL AGING AND MEIOTIC REGULATION IN OOCYTES

The goal of this research is to examine the effects of maternal aging on
the process of meiosis in the human oocyte. Women attempting to reproduce
when they are beyond their prime reproductive years often experience an
increased incidence of nondisjunction in their oocytes. This represents a
significant public health issue since more women are attempting to
reproduce at an older age than ever before. The cause of the
nondisjunction is due to abnormalities in the process of meiosis that have
yet to be identified. We have data from younger (age 20-25) and older
women (age 40-45) demonstrating that the meiotic spindle in older women is
abnormal with regard to the microtubule matrix and chromosome alignment.
This suggests that the regulatory mechanism responsible for meiotic
spindle assembly are altered in older women, thus leading to irregular
spindles and abnormal chromosome placement. There are large gaps in our
knowledge of the different phases of meiosis in the human oocyte
particularly with regard to the affects of aging. Our specific goals are
threefold: 1) To examine the patterns of chromosome movement during
meiosis in living human oocytes from different age groups followed by
examination of the expression and placement of regulatory proteins
involved in meiotic spindle assembly. 2) Analyze the recruitment of
specific cytoplasmic domains that are thought to be involved in meiosis in
the human oocyte. 3) Use an aging animal model to examine similar aspects
of meiosis during maternal aging. We hypothesize that maternal aging
causes temporal and spatial changes in chromosome movement and alteration
of specific regulatory elements during the early phases of meiosis. These
experiments will provide information on the mechanisms responsible for the
nondisjunction that often occurs due to advanced maternal age.
Identification of specific molecular events in the oocyte that are
affected by age will lead to strategies for the prevention of
nondisjunction in older women.