Neuroscience Research Center, Institute of Neuropharmachology, Kerman University of Medical Sciences, Kerman, Iran.
Department of Anatomical Sciences, School of Medicine, Kerman University of Medical Sciences, Kerman, Iran.
Sci Rep. 2021 Jun 10;11(1):12311. doi: 10.1038/s41598-021-91739-6.
It is well established that maternal lifestyle during pregnancy and lactation affects the intrauterine programming of F1 offspring. However, despite the co-use of alcohol and nicotine is a common habit, the effects of exposure to both substances on the reproductive system of F1 male offspring and the underlying mechanisms of developmental programming have not been investigated. The present study aimed to examine pre- and postnatal concurrent exposure to these substances on genetic and epigenetic alterations of sperm cells as well as testis properties of F1 offspring compared with exposure to each substance alone. Pregnant dams in the F0 generation randomly received normal saline, nicotine, ethanol, and combinations throughout full gestation and lactation periods. Sperm cells and testes of F1 male offspring were collected at postnatal day 90 for further experiments. High levels of sperm DNA fragmentation were observed in all exposed offspring. Regarding epigenetic alterations, there was a significant increase in the relative transcript abundance of histone deacetylase 1 and 2 in all exposed sperm cells. Moreover, despite a decrease in the expression level of DNA methyltransferase (DNMT) 3A, no marked differences were found in the expression levels of DNMT1 and 3B in any of the exposed sperm cells compared to non-exposed ones. Interestingly, combined exposure had less prominent effects relative to exposure to each substance alone. The changes in the testicular and sperm parameters were compatible with genetic and epigenetic alterations. However, MDA level as an oxidative stress indicator increased in all exposed pups, which may be responsible for such outputs. In conclusion, maternal co-exposure to these substances exhibited epigenotoxicity effects on germline cells of F1 male offspring, although these effects were less marked relative to exposure to each substance alone. These counteracting effects may be explained by cross-tolerance and probably less impairment of the antioxidant defense system.
众所周知，母体在妊娠和哺乳期的生活方式会影响 F1 后代的宫内编程。然而，尽管同时饮酒和吸烟是一种常见的习惯，但暴露于这两种物质对 F1 雄性后代生殖系统的影响以及发育编程的潜在机制尚未得到研究。本研究旨在检查这些物质的产前和产后同时暴露对精子细胞的遗传和表观遗传改变以及与单独暴露于每种物质相比 F1 后代睾丸特性的影响。F0 代怀孕母鼠在整个妊娠期和哺乳期随机接受生理盐水、尼古丁、乙醇和组合处理。在产后第 90 天收集 F1 雄性后代的精子细胞和睾丸进行进一步实验。所有暴露组的精子 DNA 碎片化水平均升高。关于表观遗传改变，所有暴露的精子细胞中组蛋白去乙酰化酶 1 和 2 的相对转录丰度均显著增加。此外，尽管 DNA 甲基转移酶（DNMT）3A 的表达水平下降，但与未暴露组相比，任何暴露组的精子细胞中 DNMT1 和 3B 的表达水平均无明显差异。有趣的是，与单独暴露相比，联合暴露的影响相对不明显。睾丸和精子参数的变化与遗传和表观遗传改变一致。然而，所有暴露的幼鼠的 MDA 水平（一种氧化应激标志物）均升高，这可能是导致这种结果的原因。总之，母体同时暴露于这些物质对 F1 雄性后代的生殖细胞表现出表观遗传毒性作用，尽管与单独暴露于每种物质相比，这些作用不那么明显。这些相互拮抗的作用可能是由于交叉耐受和抗氧化防御系统的损伤可能较小。
