In Utero and Lactational Exposure of F1 Adult Pups to Ethanol and Nicotine: Alteration of The Reproductive System and Epigenetic Modifying Enzymes of Sperm Cells?

Abstract

Co-use of alcohol and nicotine is a common habit which could affect reproductive system. The present study was designed to investigate the effect of in-utero and lactational exposure of offspring to alcohol, nicotine, and combinations on the reproductive system and epigenetic alterations of male gamete. Pregnant mice and lactating NMRI pups randomly received nicotine, ethanol, and combinations during gestational days 1 until weaning. Sperm and testes were collected on postnatal day 90 for further experiments. Exposure to these substances, particularly, nicotine, highly affected testicular Johnsen’s score, sperm parameters including; number, motility, viability, DNA integrity and also serum MDA level. Interestingly, concurrent exposure to nicotine and alcohol somehow reversed the effects. Quantitative real-time PCR data showed an increase in the mRNA level of histone deacetylation 1 and 2 and a decrease in the level of DNA methyltransferase (DNMT) 3A, while no marked differences in the expression level of DNMT1 and 3B were observed between the exposed and non-exposed pups. Alleviating effects were observed in the epigenetic modifying enzymes transcripts of co-exposed pups compared with the exposure to nicotine or alcohol. Taken together, our findings determined that exposure of offspring in-utero and during lactational period to these substances could result in lasting epigenetic changes in sperm cells. However, unexpectedly co-exposure of pups to nicotine and alcohol lessened these negative effects.