Genetic Association in the Maintenance of the Mitochondrial Microenvironment and Sperm Capacity

Abstract

Sperm motility is one of the major determinants of male fertility. Since sperm need a great deal of energy to support their fast movement by active metabolism, they are thus extremely vulnerable to oxidative damage by the reactive oxygen species (ROS) and other free radicals generated as byproducts in the electron transport chain. The present study is aimed at understanding the impact of a mitochondrial oxidizing/reducing microenvironment in the etiopathology of male infertility. We detected the mitochondrial DNA (mtDNA) 4,977 bp deletion in human sperm. We examined the gene mutation of ATP synthase 6 (ATPase6 m.T8993G) in ATP generation, the gene polymorphisms of uncoupling protein 2 (UCP2, G-866A) in the uncoupling of oxidative phosphorylation, the role of genes such as manganese superoxide dismutase (MnSOD, C47T) and catalase (CAT, C-262T) in the scavenging system in neutralizing reactive oxygen species, and the role of human 8-oxoguanine DNA glycosylase (hOGG1, C1245G) in 8-hydroxy-2 ′ -deoxyguanosine (8-OHdG) repair. We found that the sperm with higher motility were found to have a higher mitochondrial membrane potential and mitochondrial bioenergetics. The genotype frequencies of UCP2 G-866A, MnSOD C47T, and CAT C-262T were found to be significantly different among the fertile subjects, the infertile subjects with more than 50% motility, and the infertile subjects with less than 50% motility. A higher prevalence of the mtDNA 4,977 bp deletion was found in the subjects with impaired sperm motility and fertility. Furthermore, we found that there were significant differences between the occurrences of the mtDNA 4,977 bp deletion and MnSOD (C47T) and hOGG1 (C1245G). In conclusion, the maintenance of the mitochondrial redox microenvironment and genome integrity is an important issue in sperm motility and fertility.

Molecular and physiochemical evaluation of buck semen cryopreserved with antioxidants

“…Mitochondria metabolic activity is crucial for sperm motion and fertilizing ability (Thomas et al, 2021). Our results demonstrated up-regulation of two mitochondrial transcripts (CPT2 and ATP5F1A) that enhance metabolic activity of spermatozoa in semen groups supplemented with Cys, LC + M, LC + Cys and M + Cys.…”

“…Antioxidant capacity and metabolic activity are correlated when taken into account that some genes encoding for antioxidant enzymes (such as SOD1, SOD2 and PRDX1) are transcribed from mitochondria (Madeja et al, 2021; Saraf et al, 2021; Thomas et al, 2021). Mitochondria metabolic activity is crucial for sperm motion and fertilizing ability (Thomas et al, 2021). Our results demonstrated up‐regulation of two mitochondrial transcripts (CPT2 and ATP5F1A) that enhance metabolic activity of spermatozoa in semen groups supplemented with Cys, LC + M, LC + Cys and M + Cys.…”

“…Increased expression profile of mitochondrial proteins (ATP5A1 and ATP5B) was linked with enhanced post-thaw viability and motility of boar spermatozoa (Chen et al, 2014). On the contrary, two different investigations confirmed the presence of mtDNA 4977 bp deletion that negatively affects sperm motility (Steger et al, 2001;Thomas et al, 2021). Moreover, the abundance of genes regulating mitochondrial NADH dehydrogenase 2 (MTND2) was down-regulated in men suffering from asthenospermia (Jodar et al, 2012).…”

In-silico molecular characterization of DNAH6 and ATPase6 (Mitochondrial DNA) genes in asthenozoospermia patients in the northern region of India

“…The loss of centriole translocation may lead to physical contact between the centriole and nucleus and cause decapitated sperm(Li et al 2018). However, in accordance with Gershoni et al, a rare mutation in DNAH6 has been shown to be associated with azoospermia patients(Gershoni et al 2017).In the last few years, mutation in mitochondrial DNA (mtDNA) or ATP-generating genes has been noted to infer changes in sperm motility(Shamsi et al 2011;Thomas et al 2021). The role of mtDNA in male infertility was rst correlated in early 1990 when scientists reported reduced sperm motility in individuals having structural defects in mitochondria.…”

“…Genetic factors involved in male infertility manifest as chromosomal disorders, mitochondrial DNA (mtDNA) mutations, monogenic disorders, multifactorial disorders, and endocrine disorders of genetic origin. Male infertility is often related to chromosome abnormalities or other genetic factors (Holyoake et al 2002;Nakada et al 2006; Elrahman et al 2021;Thomas et al 2021). DNAH6 (Dynein Axonemal Heavy Chain 6) is a protein-coding gene, part of the microtubule-associated motor protein and is a testis-speci c-expressed protein, located in the neck region of the spermatozoa, required for the function of cilia function in spermatozoa (Li et al 2017).…”