The fetal origins of adult disease theory links early developmental events with diseases including heart disease, diabetes, cancer and depression[1]. Additionally a growing body of evidence suggests that fertility may also be affected by the fetal environment. Mammalian oocyte development begins in fetal life and so environmental and lifestyle factors of the mother could directly impact the fertility of the subsequent generation. Cigarette smoking is a known ovotoxicant in active smokers, yet disturbingly 13% of pregnant Australian women continue to smoke. The focus of our investigation was to characterise the adverse effects of smoking on ovaries of female offspring exposed in utero. Pregnant mice were nasally exposed to cigarette smoke for 12 weeks (human equivalent of a pack-a-day smoking) throughout pregnancy/lactation and oocyte number and quality of the F1 generation examined. In utero exposure to cigarette smoke significantly reduced the number of ovulated oocytes. These oocytes exhibited enhanced lipid peroxidation, mitochondrial ROS leakage, decreased metaphase II spindle size and reduced zona pellucida thickness. Together with a decrease in sperm-zona and sperm-oolemma binding, reduced litter sizes and increased time to conception, our data indicates that in utero exposure to cigarette smoke produces oocytes of poor quality. Previous studies have also found that in utero exposure to the constituents of cigarette smoke causes epigenetic changes in the fetus, which can impact the health of the subsequent F2 generation [2]. Consistent with such a model, investigation of oocyte quality in the F2 generation revealed an altered metaphase II spindle and increased interkinetochore distances which might influence the ability of the oocyte to undergo correct chromosome segregation. Collectively our results demonstrate that in utero exposure to cigarette smoke has a transgenerational effect upon female fertility which manifests as an overt reduction in oocyte quality at the F1 and F2 generations.
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