Genetic and epigenetic modifications of F1 offspring's sperm cells following in utero and lactational combined exposure to nicotine and ethanol.

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.

Effects of ethanol and nicotine co-administration on follicular atresia and placental histo-morphology in the first-generation mice pups during intrauterine development and lactation periods.

This study is evaluating the effects of ethanol and nicotine exposure during pregnancy and lactation on placenta histology and follicular atresia in the first-generation (f1) mice pups. The experimental groups were 5 groups of NMRI pregnant mice, including: control, vehicle (received normal saline) ethanol (3 g/kg/day, 20 % v/v intraperitoneally), nicotine (1 mg/kg/day, subcutaneously), and ethanol plus nicotine which received both. Pregnant animals in each group were then divided into two groups, one group for examining the placenta that was treated for 18 days and the other group for the ovary of one-day-old (PND1) and fifty-six-day-old (PND56) female offspring who were treated for 42 days (during intrauterine development and lactation). After the autopsy procedure, histopathological and morphometrical observations were done. Data revealed that the exposed mice had a significant change in the placenta morphometry and histology as well as a marked increase in the number of ovarian TUNEL positive cells on postnatal days 1 and 56. Therefore, maternal exposure to alcohol and nicotine during developmental and lactation periods could lead to changes in the placenta properties as well as an increase in the apoptotic ovarian follicles in f1 mice pups.