Nicotine exposure impairs germ cell development in human fetal ovaries cultured in vitro.

Shun-Feng Cheng,Lan Li,Yong Zhao,Fan Yang,Yi Zhou,Shu-Hua Zou,Yan-Ni Feng,Wei Ge,Xun-Si Qin,Wei Shen,Massimo De Felici,Xiao-Feng Sun,Ze-Li Han

doi:10.18632/aging.101492

Abstract

In the present paper, we found that human fetal ovaries (at ~16 weeks) express the transcripts for several subunits of the nicotinic acetylcholine receptor (nAChR). Exposure to the drug in vitro resulted in the marked increase of apoptosis in the ovaries in a time and dose-dependent manner. Evidence that adverse nicotine effects are potentially due to an increased level of reactive oxygen species (ROS) and consequent DNA damage, both in the ovarian somatic cells and germ cells, are reported. After 4 days of culture, exposure to 1 mM and 10 mM nicotine caused a 50% and 75% decrease, respectively, in the number of oogonia/oocytes present in the fetal ovaries. These results represent the first indication that nicotine may directly cause apoptosis in cells of the fetal human ovary and may lead to a reduction of the ovarian reserve oocytes and consequent precocious menopause in mothers smoking during pregnancy.

Highlights

The adverse effects of maternal tobacco smoke on fetuses have been well documented for more than three decades and remains one of the main preventable causes of perinatal complications
In a first series of experiments, we investigated the expression of nicotinic acetylcholine receptors www.aging‐us.com in the ovary using qRT-PCR
The results showed that the ovaries expressed the transcripts of various subunits of nicotinic acetylcholine receptor (nAChR), and that exposure for 4 days to 1 mM nicotine significantly increased the mRNA level of some subunits, namely nAChRα1, 2, 3 and 9, in comparison to control, while 10mM nicotine caused, almost invariably, a decrease of the transcript levels of most of the subunits (Figure 1)

Summary

Introduction

The adverse effects of maternal tobacco smoke on fetuses have been well documented for more than three decades and remains one of the main preventable causes of perinatal complications. Evidence is accumulating that components present in cigarette smoke can affect the prenatal development of the reproductive organs including the ovaries in exposed offspring [3,4,5,6,7]. After entering into the GRs (7-9 weeks gestation), PGCs, called oogonia, undergo several rounds of mitotic division leading to a large increase in their numbers [9]. Mitotic divisions of oogonia end around the 18th week www.aging‐us.com of gestation, reaching a peak number of germ cells at 67 million. Female germ cells lose the ability to divide mitotically and are termed oocytes. During late gestation a large number of oogonia and oocytes undergo cell death which reduces the germ cell population to ~1-2 million at birth. All gametogenesis processes reported above are potentially vulnerable to environmental pollutants that can impact the fertility of females postnatally [13, 14]

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Conclusion