The impact of mitochondrial genetics on male infertility

Abstract

Summary Human mitochondrial DNA (mtDNA) encodes 13 of the polypeptides associated with the process of oxidative phosphorylation (OXPHOS), the cells most important ATP generating pathway. Until recently, the effects of mtDNA rearrangements on male fertility have been largely ignored. However, it is becoming increasingly evident that both point mutations and large-scale deletions may have an impact on sperm motility and morphology. We discuss the implications of these rearrangements in the context of the clinical setting. We further discuss the possible consequences resulting from the transmission of sperm mtDNA deletions to the offspring. The role of nucleo-cytoplasmic interaction is investigated in the context of nuclear transcription and replication factors that regulate mtDNA transcription and replication.

Mitochondria functionality and sperm quality

“…Furthermore, oxygen consumption in sperm mitochondria and mitochondrial respiratory efficiency also correlate with motility (Stendardi et al 2011, Ferramosca et al 2012, and many different ETC inhibitors (Fig. 1) have been shown to negatively affect sperm motility (Ruiz-Pesini et al 2000b, St John et al 2005. Given that these results depend on an organized ETC (rather than on the activity of individual components), the data suggest that a functional organelle is important for sperm function.…”

A multi-faceted approach to understanding male infertility: gene mutations, molecular defects and assisted reproductive techniques (ART)

“…Recent reports have shown that mtDNA point mutations or multiple deletions, mtDNA single nucleotide polymorphisms (SNPs) and mtDNA haplogroups can greatly influence sperm quality and are associated with asthenozoospermia or oligoasthenozoospermia [128][129][130][131][132][133][134][135][136][137][138]. Among the mitochondrial deletions observed, the deletion of 4977 bp was the most prevalent and abundant one.…”

CAG-repeat variant in the polymerase γ gene and male infertility in the Chinese population: a meta-analysis

“…2 Because spermatozoa contain a large number of mitochondria and mitochondria have an important role in the quality and quantity of spermatozoa by providing the energy needed to complete their functions, especially sperm motility, 3 it is generally hypothesized that the accumulation of pathogenic mitochondrial DNA (mtDNA) influences the function of spermatozoa, including sperm motility. 4 A series of studies have noted an association between alterations of mtDNA and sperm dysfunction. 4 DNA polymerase c (POLG), which is encoded by the POLG gene, is the only known DNA polymerase for mtDNA replication and maintenance in human beings.…”

“…4 A series of studies have noted an association between alterations of mtDNA and sperm dysfunction. 4 DNA polymerase c (POLG), which is encoded by the POLG gene, is the only known DNA polymerase for mtDNA replication and maintenance in human beings. The human POLG gene is located on 15q24-15q26, spans 23 exons and includes a trinucleotide CAG-repeat region that encodes a polyglutamine stretch near the N-terminus of the mature protein, downstream of the presumed mitochondrial targeting sequence.…”