Wang Yu-Feng, Sun Xiao-Feng, Han Ze-Li, Li Lan, Ge Wei, Zhao Yong, De Felici Massimo, Shen Wei, Cheng Shun-Feng
College of Animal Science and Technology, Qingdao Agricultural University, Qingdao 266109, China.
College of Life Sciences, Institute of Reproductive Sciences, Qingdao Agricultural University, Qingdao 266109, China.
Aging (Albany NY). 2018 Mar 28;10(3):463-480. doi: 10.18632/aging.101405.
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 , , and . 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. 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.
在本文中，我们表明连续五天注射尼古丁的新生小鼠表现出生殖细胞囊肿破裂和原始卵泡组装受损，导致卵巢储备减少，这种情况持续到性成熟年龄。尼古丁对幼鼠卵巢的影响与卵母细胞特异性基因如 、 、 和 的表达降低有关。此外，注射尼古丁的幼鼠卵巢显示细胞氧化应激水平和自噬标志物增加（AMPKα-1上调，LC3-II/LC3-I比值增加，AKT和mTOR下调）。值得注意的是，1 μM褪黑素的给药抵消了所有这些影响。在10 μM尼古丁存在的情况下，将0日龄幼鼠的卵巢培养5天再现了其对生殖细胞囊肿破裂和原始卵泡组装的影响，此外还显示体细胞增殖减少约20%，当向培养基中添加褪黑素时，这些影响得到预防。综上所述，这些结果表明，尼古丁暴露可能通过局部诱导细胞应激改变原始卵泡组装，从而对小鼠卵巢储备的建立产生不利影响，然而，褪黑素能够抵消这种影响。
