Human mtDNA Haplogroups Associated with High or Reduced Spermatozoa Motility

Abstract

A variety of mtDNA mutations responsible for human diseases have been associated with molecular defects in the OXPHOS system. It has been proposed that mtDNA genetic alterations can also be responsible for sperm dysfunction. In addition, it was suggested that if sperm dysfunction is the main phenotypic consequence, these mutations could be fixed as stable mtDNA variants, because mtDNA is maternally inherited. To test this possibility, we have performed an extensive analysis of the distribution of mtDNA haplogroups in white men having fertility problems. We have found that asthenozoospermia, but not oligozoospermia, is associated with mtDNA haplogroups in whites. Thus, haplogroups H and T are significantly more abundant in nonasthenozoospermic and asthenozoospermic populations, respectively, and show significant differences in their OXPHOS performance.

Mitochondrial DNA haplogroup associated with sperm motility in the Han population

“…We should pay attention to the probability that many different polymorphisms may militate against mitochondrial function together vs. single base differences. Ruiz-Pesini et al 6 demonstrated the existence of variable complex IV-specific and cytochrome c oxidase activities between haplotypes H and T. Variable complex I-specific activities were included in our investigation perhaps due to different mtDNA haplogroup polymorphisms.…”

“…In the study by Ruiz-Pesini et al, 6 mtDNA haplotype H was found to be underrepresented and haplotype T was overrepresented in men with asthenozoospermic ejaculates. Furthermore, significant differences in OXPHOS component activity were found between different haplotypes.…”

“…9 Several studies have also investigated mtDNA and sperm function in humans. The most famous study of mtDNA haplotype variation on sperm motility was reported by Ruiz-Pesini et al 6 The authors showed that haplotype H was underrepresented and haplotype T was overrepresented in men with asthenozoospermic ejaculates, and a subsequent study provided some support for these findings. 10 However, other studies failed to identify an association between mtDNA and either sperm motility 11,12 or cellular bioenergetic parameters.…”

“…These mtDNA variants create clusters of related mtDNA haplotypes known as haplogroups. 5 A considerable body of data suggests that mtDNA haplogroups have functional importance, being associated with respiratory-chain activity 6 and disease susceptibility, such as Alzheimer's disease, 7 Parkinson's disease 8 and severe sepsis. 9 Several studies have also investigated mtDNA and sperm function in humans.…”

Mitochondrial DNA haplogroups: Role in the prevalence and severity of knee osteoarthritis

“…Among Europeans, 95% of the population belongs to 1 of 9 haplogroups: H, I, J, K, T, U, V, W, or X. Given the lines of evidence that describe the contribution of mtDNA to cellular physiology, as well as its critical importance for energy production, a number of studies have investigated the association between mtDNA haplogroups and multifactorial diseases (22)(23)(24)(25)(26)(27)(28), mitochondrial diseases (29,30), and aging (31)(32)(33).…”