Novel insights into the genetic and epigenetic paternal contribution to the human embryo

The integrity of the sperm genome and epigenome are critical for normal embryonic development. The advent of assisted reproductive technology has led to an increased understanding of the role of sperm in fertilization and embryogenesis. During fertilization, the sperm transmits not only nuclear DNA to the oocyte but also activation factor, centrosomes, and a host of messenger RNA and microRNAs. This complex complement of microRNAs and other non-coding RNAs is believed to modify important post-fertilization events. Thus, the health of the sperm genome and epigenome is critical for improving assisted conception rates and the birth of healthy offspring.

DAZL 260A>G and MTHFR 677C>T variants in sperm DNA of infertile Indian men.

DAZL (deleted in azoospermia-like) 260A>G and MTHFR (methylene tetrahydrofolate reductase) 677C>T are two important autosomal variants associated with impaired spermatogenesis. In this study, we investigated DAZL 260A>G and MTHFR 677C>T variants in sperm DNA and their frequency in oligozoospermic infertile men of Indian origin. The study on sperm DNA was performed, since it is more prone to oxidative stress-induced damage and mutation. One hundred oligozoopsermic infertile men having normal chromosomal complement with intact Y chromosome and 100 age- and ethnically-matched fertile controls were investigated for these variants in their sperm genome. Spermatozoa were separated by gradient centrifugation and DNA was isolated and analyzed for the single nucleotide polymorphisms (SNPs) by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). The results showed no significant differences in the frequency of DAZL AG (P = 0.58) and MTHFR CT (P = 0.44) between oligozoospermic infertile men and controls. However, 8% (8/100) oligozoospermic infertile men harbored both the variants and showed significantly (P<0.0001) lower sperm count (3.28 ± 1.1 vs 12.50 ± 4.09) compared to infertile men with either of the single variant. None of the fertile controls showed the presence of the both variants. In conclusion, the combined effect of both DAZL 260A>G and MTHFR 677C>T variants may have role in compromised sperm count. However, further studies are required to find the pathological role of these combined variants in male infertility.