Research Article: Protective effects of melatonin against nicotine-induced disorder of mouse early folliculogenesis

Date Published: March 28, 2018

Publisher: Impact Journals

Author(s): Yu-Feng Wang, Xiao-Feng Sun, Ze-Li Han, Lan Li, Wei Ge, Yong Zhao, Massimo De Felici, Wei Shen, Shun-Feng Cheng.


In this paper, we show that neonatal mice injected for five consecutive days with nicotine display impaired germ cell cyst breakdown and primordial follicle assembly resulting in decreased ovarian reserve lasting until sex maturation age. The effects of nicotine on the pups ovaries were associated with decreased expression of oocyte specific genes such as Nobox, Lhx8, Figlα and Sohlh2. Moreover, the ovaries of pups injected with nicotine showed increased level of cell oxidative stress and autophagic markers (upregulation of AMPKα-1, increased ratio LC3-II/LC3-I, downregulation of AKT and mTOR). Noteworthy, all these effects were counteracted by the administration of the hormone melatonin in 1 μM. In vitro culture of 0 dpp ovaries for 5 days in the presence of 10 μM nicotine reproduced its effect on germ cell cyst breakdown and primordial follicle assembly, furthermore it also revealing about 20% reduction of somatic cells proliferation, and these effects was prevented when melatonin was added to the medium. Taken together these results show that nicotine exposure can adversely affect the establishment of the ovarian reserve in the mouse likely by locally inducing cellular stress altering the primordial follicle assembly and that melatonin, however, is able to counteract such effects.

Partial Text

Smoking is a well-established risk factor for many human health conditions, including increased risk of subfertility, infertility and pregnancy loss [1,2]. The incidence of smoking has generally fallen over the last 20 years but significant numbers of women continue to smoke before and during pregnancy. Total 13-25% of pregnancies are exposed tobacco smoke in many countries [3]. There are evidences that in utero exposure to cigarette smoke has long-term consequences on the fertility of the offspring, including reproductive abnormalities and reduced fertility [2]. Indeed, the daughters of mothers who smoked during pregnancy have an earlier menopause, shorter reproductive lifespan, and reduced fecund ability [2,4,5].

There is a plethora of evidence linking smoking to a host of adverse health outcomes including infertility by generation of free radicals [17–19]. However, the studies in the effect of nicotine on the establishment of the primordial follicle pool are very limited. The current study provides evidence that neonatal mouse ovary development is vulnerable to daily intraperitoneal administration of nicotine, which alters germ cell cyst breakdown and primordial follicle assembly. Furthermore, we also showed exposure to nicotine impaired primordial follicle formation by activation of the autophagy pathway.




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