During the last decades the study of male infertility & the introduction of the assisted reproductive techniques (ARTs) has allowed to understand that normal sperm parameters do not always predict fertilization. Sperm genetic components could play an important role in the early stages of embryonic development. Based on these acquisitions, several epigenetic investigations have been developed on spermatozoa, with the aim of understanding the multifactorial etiology of male infertility & of showing whether embryonic development may be influenced by sperm epigenetic abnormalities. This article reviews the possible epigenetic modifications of spermatozoa & their effects on male fertility, embryonic development & ART outcome. It focuses mainly on sperm DNA methylation, chromatin remodeling, histone modifications & RNAs.
A session "Epigenetics in reproductive health" going to be held at Vienna.
Epigenetics process is the heritable
change in gene function that does not involve changes in the DNA sequence.
Until now, several types of epigenetic mechanisms have been characterized,
including DNA methylation, histone modification (acetylation, methylation,
etc.) nucleosome remodeling, and noncoding RNAs. With the biological
investigations of these modifiers, some of them are identified as promoters in
the process of various diseases, such as cancer, cardiovascular disease and
virus infection. Epigenetic changes may serve as potential "first
hits" for tumorigenesis. Hence, targeting epigenetic modifiers is being
considered as a promising way for disease treatment. To date, six agents in two
epigenetic target classes (DNMT and HDAC) have been approved by the US Food and Drug Administration (FDA).
Most of these drugs are applied in leukemia, lymphoma therapy, or are combined
with other drugs for the treatment of solid tumor. Due to the rapid development
of epigenetics and epigenetics targeted drugs, it is becoming an emerging area in targeted drug design.
Hypermethylation of CpG islands in the promoter
region of many tumor suppressor genes downregulates their expression & in a
result promotes tumorigenesis. Therefore, detection of DNA methylation status
is a convenient diagnostic tool for cancer detection. Here, we reported a novel
method for the integrative detection of methylation by the microfluidic
chip-based digital PCR. This method relies on methylation-sensitive restriction
enzyme HpaII, which cleaves the unmethylated DNA strands while keeping the methylated
ones intact. After HpaII treatment, the DNA methylation level is determined
quantitatively by the microfluidic chip-based digital PCR with the lower limit
of detection equal to 0.52%. To validate the applicability of this method,
promoter methylation of two tumor suppressor genes (PCDHGB6 and HOXA9) was
tested in 10 samples of early stage lung adenocarcinoma and their adjacent
non-tumorous tissues. The consistency was observed in the analysis of these
samples using our method and a conventional bisulfite pyrosequencing. Combining
high sensitivity & low cost, the microfluidic chip-based digital PCR method
might provide a promising alternative for the detection of DNA methylation
& early diagnosis of epigenetics-related diseases.
Epidemiological
evidence increasingly suggests that environmental exposures early in
development have a role in susceptibility to disease in later life. In
addition, some of these environmental effects seem to be passed on through
subsequent generations. Epigenetic modifications provide a plausible link
between the environment and alterations in gene expression that might lead to
disease phenotypes. An increasing body of evidence from animal studies supports
the role of environmental epigenetics in disease susceptibility. Furthermore,
recent studies have demonstrated for the first time that heritableenvironmentally induced epigenetic modifications underlie reversible
transgenerational alterations in phenotype. Methods are now becoming available
to investigate the relevance of these phenomena to human disease.
