BackgroundInfertility is a common reproductive disorder, with male factor infertility accounting for approximately half of all cases. Taking a paternal perceptive, recent research has shown that sperm epigenetics, such as changes in DNA methylation, histone modification, chromatin structure, and noncoding RNA expression, can impact reproductive and offspring health. Importantly, environmental conditions during the preconception period has been demonstrated to shape sperm epigenetics.ObjectivesTo provide an overview on epigenetic modifications that regulate normal gene expression and epigenetic remodeling that occurs during spermatogenesis, and to discuss the epigenetic alterations that may occur to the paternal germline as a consequence of preconception environmental conditions and exposures.Materials and methodsWe examined published literature available on databases (PubMed, Google Scholar, ScienceDirect) focusing on adult male preconception environmental exposures and sperm epigenetics in epidemiologic studies and animal models.ResultsThe preconception period is a sensitive developmental window in which a variety of exposures such as toxicants, nutrition, drugs, stress, and exercise, affects sperm epigenetics.Discussion and ConclusionUnderstanding the environmental legacy of the sperm epigenome during spermatogenesis will enhance our understanding of reproductive health and improve reproductive success and offspring well‐being.

Parental age at time of offspring conception is increasing in developed countries. Advanced male age is associated with decreased reproductive success and increased risk of adverse neurodevelopmental outcomes in offspring. Mechanisms for these male age effects remain unclear, but changes in sperm DNA methylation over time is one potential explanation. We assessed genome-wide methylation of sperm DNA from 47 semen samples collected from male participants of couples seeking infertility treatment. We report that higher male age was associated with lower likelihood of fertilization and live birth, and poor embryo development (p < 0.05). Furthermore, our multivariable linear models showed male age was associated with alterations in sperm methylation at 1698 CpGs and 1146 regions (q < 0.05), which were associated with > 750 genes enriched in embryonic development, behavior and neurodevelopment among others. High dimensional mediation analyses identified four genes (DEFB126, TPI1P3, PLCH2 and DLGAP2) with age-related sperm differential methylation that accounted for 64% (95% CI 0.42–0.86%; p < 0.05) of the effect of male age on lower fertilization rate. Our findings from this modest IVF population provide evidence for sperm methylation as a mechanism of age-induced poor reproductive outcomes and identifies possible candidate genes for mediating these effects.

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Background: Currently, the precise mechanisms that underline male infertility are still unclear. Accumulating data implicate non-coding RNA cargo of seminal plasma extracellular vesicles due to their association with poor semen quality and higher expression levels relative to vesicle-free seminal plasma. Method: We assessed sperm-free seminal plasma extracellular vesicle non-coding RNA profiles from 91 semen samples collected from male participants of couples seeking infertility treatment. Men were classified into two groups (poor, n = 32; normal, n = 59) based on World Health Organization semen cutoffs. Small RNA sequencing reads were mapped to standard biotype-specific transcriptomes in the order micro RNA > transfer RNA > piwi-interacting RNA > ribosomal RNA > ribosomal RNA > circular RNA > long non-coding RNA using STAR. Differential expression of normalized non-coding RNA read counts between the two groups was conducted by EdgeR (Fold change ≥1.5 and (false discovery rate [FDR] < 0.05). Result: Small RNA sequencing identified a wide variety of seminal plasma extracellular vesicle non-coding RNA biotypes including micro RNA, ribosomal RNAs, piwi-interacting RNAs, transfer RNA, long non-coding RNAs as well as circular RNAs, and fragments associated with pseudogenes, and nonsense-mediated decay. The expression levels of 57 seminal plasma extracellular vesicle non-coding RNAs (micro

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