PT  - JOURNAL ARTICLE
AU  - Yan Yun
AU  - Zijie Wei
AU  - Neil Hunter
TI  - Maternal Obesity Enhances Oocyte Chromosome Abnormalities Associated With Aging
AID  - 10.1101/505511
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 505511
4099  - http://biorxiv.org/content/early/2018/12/23/505511.short
4100  - http://biorxiv.org/content/early/2018/12/23/505511.full
AB  - Obesity is increasing globally and maternal obesity has adverse effects on pregnancy outcomes and the long-term health of offspring. Maternal obesity has been associated with pregnancy failure through impaired oogenesis and embryogenesis. However, whether maternal obesity causes chromosome abnormalities in oocytes has remained unclear. Here we show that chromosome abnormalities are increased in the oocytes of obese mice and identify weakened sister-chromatid cohesion as the likely cause. Numbers of full-grown follicles retrieved from obese mice were the same as controls and the efficiency of in vitro oocyte maturation remained high. However, chromosome abnormalities presenting in both metaphase-I and metaphase-II were elevated, most prominently the premature separation of sister chromatids. Weakened sister-chromatid cohesion in oocytes from obese mice was manifested both as the terminalization of chiasmata in metaphase-I and as increased separation of sister centromeres in metaphase II. Obesity-associated abnormalities were elevated in older mice implying that maternal obesity exacerbates the deterioration of cohesion seen with advancing age.We thank Richard Shultz and members of the Hunter Lab for support and discussions. N.H. is an Investigator of the Howard Hughes Medical Institute, which also supported this study.