Association of Sperm Methylation at LINE-1, Four Candidate Genes, and Nicotine/Alcohol Exposure With the Risk of Infertility

Abstract

In this study, we examined whether smoking and drinking affect sperm quality and the DNA methylation of the repetitive element LINE-1, MEST, P16, H19, and GNAS in sperm. Semen samples were obtained from 143 male residents in a minority-inhabited district of Guizhou province in southwest China. Quantitative DNA methylation analysis of the samples was performed using MassARRAY EpiTYPER assays. Sperm motility was significantly lower in both the nicotine-exposed (P = 0.0064) and the nicotine- and alcohol-exposed (P = 0.0008) groups. Follicle-stimulating hormone (FSH) levels were higher in the nicotine-exposed group (P = 0.0026). The repetitive element LINE-1 was hypermethylated in the three exposed groups, while P16 was hypomethylated in the alcohol and both the alcohol and nicotine exposure groups. Our results also show that alcohol and nicotine exposure altered sperm cell quality, which may be related to the methylation levels of MEST and GNAS. In addition, MEST, GNAS, and the repetitive element LINE1 methylation was significantly associated with the concentration of sperm as well as FSH and luteinizing hormone levels.

Minor DNA methylation changes are observed in spermatozoa prepared using different protocols

“…The field of human reproduction is no exception in following this trend, as studying epigenetic changes in gametes is even more interesting considering that gametes are responsible for transferring genetic material to the next generation 11 . Lately, a number of studies exploring sperm DNA methylation from different angles have been published, 12‐18 but there is a lack of studies on how different sperm preparation methods could possibly influence the sperm DNA methylation profile. To our knowledge, only one study has explored the DNA methylation profile of spermatozoa after DGC sperm preparation, 22 which is one of the most often used sperm preparation method in assisted reproduction 23 .…”

“…Consequently, this can affect the outcome of in vitro fertilization (IVF) procedures in terms of abnormal embryogenesis and pregnancy rates 13,14 . In studies on sperm DNA methylation, whole‐genome methylation analysis can be performed 13‐15 but often, only particular regions or genes are examined exclusively, for instance, regions and genes that are known to have specific paternal or maternal imprinting 16‐18 . Thus, these genes or regions are expressed only from one parental allele and around 100 such imprints have been found in mammalian genomes 19 …”

Idiopathic Infertility as a Feature of Genome Instability

“…It is unclear in what way the sperm epigenome is sensitive to potential mutagens and how these factors impact fertility parameters. Recent investigations have confirmed a link between potentially damaging agents and disruption to epigenetic processes [ 92 , 93 ], however, several studies have reported controversial results [ 94 ].…”

Global DNA Methylation as a Potential Underlying Mechanism of Congenital Disease Development

“…The DMRs are established during gametogenesis at imprinted and non-imprinted loci and are susceptible to environmental factors [65,66]. LINE-1 methylation in sperm could be a risk marker of infertility in man at nicotine/alcohol exposure [67]. It is also possible to alter DNA methylation levels and patterns within intact mammalian cells by treatment with various chemical inhibitors, DNA-demethylating drugs, which have recently been introduced as potential therapeutic agents for the treatment of human diseases, particularly myelodysplastic syndromes [68].…”

“…The dynamic reprogramming and other epigenetic patterns which could affect normal patterns of gene expression/genome stability during development could lead to an increased risk of CAs or complex diseases later in life [65][66][67].…”