Melatonin ameliorates murine fetal oocyte meiotic dysfunction in F1 and F2 offspring caused by nicotine exposure during pregnancy

Wen-Xiang Liu, Shao-Jing Tan, Yu-Feng Wang, Lan Li, Xiao-Feng Sun, Jing Liu, Francesca Gioia Klinger, Massimo De Felici, Wei Shen, Shun-Feng Cheng

Environmental Pollution 263 (2020) 114519 – Received 30 October 2019 Received in revised form, 24 December 2019, Accepted 31 March 2020, Available online 14 April 2020


Although there is abundant evidence to demonstrate that maternal smoking during pregnancy will harm the health of future generations, the impact of nicotine use by pregnant woman upon the oogenesis and folliculogenesis of female offspring has not been as widely scrutinized. Here we focus on the effects of nicotine on the meiotic progression of fetal oocytes. The data indicated that in pregnant mice treated with nicotine, intracellular ROS increased in follicles within the fetal ovary. Excessive intracellular hydrogen peroxide (H2O2) and superoxide anion (O2-) decreased mitochondrial membrane potential, inducing mitochondrial dysfunction, triggering an autophagic cascade and inhibiting anti-autophagic proteins. Fetal oocytes in F1 offspring of pregnant mice treated with nicotine exhibited a delay in meiotic prophase I, especially from the stage of pachytene to diplotene. In pubertal F1 offspring we observed a reduced number of follicles; the same reduction was also observed in F2 offspring. Of note, we found that melatonin ameliorated nicotine-induced oocyte damage and increased the expression of MnSOD, which decreased the production of nicotine-induced intracellular ROS. In addition, melatonin also maintained normal H3K4 and H3K9 di- and tri-methylation in F1 and F2 ovaries. Taken together, the current evidence suggests that, in the mouse, melatonin could prevent nicotine-impaired fetal oogenesis and folliculogenesis in offspring.

Keywords: Nicotine – Melatonin – Meiotic progression – ROS – Folliculogenesis – Inter-generational transmission