Transgenerational effects of maternal exposure to nicotine on structures of pituitary-gonadal axis of rats.

Smoking can lead to several diseases and cause a reduction in fertility in men and women. Among the various components of cigarettes harmful during pregnancy, nicotine stands out. It can cause a reduction in placental blood flow, compromising the development of the baby with neurological, reproductive and endocrine consequences. Thus, we aimed to evaluate the effects of nicotine on the pituitary-gonadal axis of rats exposed during pregnancy and breastfeeding (1st generation - F1), and whether the possible damage observed would reach the 2nd generation (F2). Pregnant Wistar rats received 2 mg/kg/day of nicotine throughout the entire gestation and lactation. Part of the offspring was evaluated on the first neonatal day (F1) for macroscopic, histopathological and immunohistochemical analyses of brain and gonads. Another part of the offspring was kept until 90 days-old for mating and obtainment of progenies that had the same parameters evaluated at the end of pregnancy (F2). The occurrence of malformations was more frequent and diversified in nicotine-exposed F2. Brain alterations, including reduced size and changes in cell proliferation and death, were seen in both generations of nicotine-exposed rats. Male and female gonads of F1 exposed rats were also affected. The F2 rats showed reduced cellular proliferation and increased cell death on the pituitary and ovaries, besides increased anogenital distance in females. The number of mast cells was not enough altered to indicate an inflammatory process in brain and gonads. We conclude that prenatal exposure to nicotine causes transgenerational alterations in the structures of pituitary-gonadal axis in rats.

Does maternal exposure to nicotine affect the oocyte quality and reproductive capacity in adult offspring?

Gonadal development begins in the intrauterine phase and females from most species are born with an established oocyte reserve. Exposure to drugs during gestation can compromise the offspring health, also affecting the gametes quality. Nicotine, the main component of cigarettes, is an oxidant agent capable of altering the fertility in men and women. As female gametes are susceptible to oxidative stress, this drug can damage the oolemma and affect oocyte maturation, induce errors during chromosomal segregation and DNA fragmentation. Oocyte mitochondria are particularly susceptible to injuries, contributing to the oocyte quality loss and embryonic development disruption. Thus, considering the high number of women who smoke during pregnancy, while significant events are occurring in the embryo for future fertility of offspring, we seek to verify the quality of the oocytes from adult rats exposed to nicotine during intrauterine phase and breastfeeding. Pregnant Wistar rats received nicotine by osmotic mini-pumps and the female progenies were evaluated in adulthood for oocyte quality (viability, lipid peroxidation, generation of reactive oxygen species and mitochondrial integrity) and reproductive capacity. Embryos (3dpc) and fetuses (20dpc) generated by these rats were also evaluated. The results showed that the dose of 2 mg/kg/day of nicotine through placenta and breast milk does not affect the number of oocytes and the fertility capacity of adult rats. However, it causes some morphological alterations in oocytes, mitochondrial changes, embryonic fragmentation and disruption of fetal development. The malformations in fetuses generated from these gametes can also indicate the occurrence of epigenetic modifications.