Mitochondria-related male infertility

TLDR

Approximately 15 % of human couples experience infertility, half of which is male and often due to low sperm motility or count, and mitochondrial DNA mutations suggest that defects in mitochondrial respiration may contribute to male infertility. The study used a transmitochondrial mouse model carrying wild‑type and mutant mtDNA with a 4,696‑bp deletion to test whether mitochondrial respiration defects cause male infertility. The authors generated mito‑mice with either wild‑type or mutant mtDNA and evaluated sperm motility, count, morphology, and testicular histology. Mito‑mice with accumulated ΔmtDNA displayed oligospermia, asthenozoospermia, sperm midpiece and nuclear abnormalities, meiotic arrest at the zygotene stage, and increased apoptosis, demonstrating that impaired mitochondrial respiration causes male infertility.

Abstract

Approximately 15% of human couples are affected by infertility, and about half of these cases of infertility can be attributed to men, through low sperm motility (asthenozoospermia) or/and numbers (oligospermia). Because mitochondrial genome (mtDNA) mutations are identified in patients with fertility problems, there is a possibility that mitochondrial respiration defects contribute to male infertility. To address this possibility, we used a transmitochondrial mouse model (mito-mice) carrying wild-type mtDNA and mutant mtDNA with a pathogenic 4,696-bp deletion (ΔmtDNA). Here we show that mitochondrial respiration defects caused by the accumulation of ΔmtDNA induced oligospermia and asthenozoospermia in the mito-mice. Most sperm from the infertile mito-mice had abnormalities in the middle piece and nucleus. Testes of the infertile mito-mice showed meiotic arrest at the zygotene stage as well as enhanced apoptosis. Thus, our in vivo study using mito-mice directly demonstrates that normal mitochondrial respiration is required for mammalian spermatogenesis, and its defects resulting from accumulated mutant mtDNAs cause male infertility.