Sperm Mitochondria, the Driving Force Behind Human Spermatozoa Activities: Its Functions and Dysfunctions - A Narrative Review

Abstract

Male infertility is a major issue and numerous factors contribute to it. One of the important organelles involved in the functioning of human spermatozoa is mitochondria. There are 50-75 mitochondria helically arranged in mid-piece bearing one mitochondrial DNA each. Sperm mitochondria play a crucial role in sperm functions including the energy production required for sperm motility, production of reactive oxygen species which in the physiological range helps in sperm maturation, capacitation, and acrosome reaction. It also plays a role in calcium signaling cascades, intrinsic apoptosis, sperm hyperactivation. Any structural or functional dysfunction of sperm mitochondria results in increased production of reactive oxygen species and a state of oxidative stress, decreased energy production, all leading to sperm DNA damage, impaired sperm motility and semen parameters, and reduced male fertility. Furthermore, human sperm mitochondrial DNA mutations can result in impaired sperm motility and parameters leading to male infertility. Numerous types of point mutations, deletions, missense mutations have been identified in mtDNA that are linked with male infertility. Methods: Recent literature was searched from English language peer-reviewed journals from databases including PubMed, Scopus, EMBASE, Scholar, Web of Science till September 2021. Search terms used were “Sperm mitochondria and male fertility”; “Bioenergetics of sperm”; “Sperm mitochondria and reactive oxygen species”, “Sperm mitochondrial mutations and infertility”. Conclusion: Sperm mitochondria is an important organelle involved in various functions of human spermatozoa and sperm mitochondrial DNA, has emerged as one of the potent biomarkers of sperm quality and male fertility.

Map-1a regulates Sertoli cell BTB dynamics through the cytoskeletal organization of microtubule and F-actin

“…Second, the acrosome is formed by the vacuoles of the Golgi body by filling with lytic enzymes (e.g., acrosin) and forming a cap-like structure at the anterior end of the spermatid head [ 88 , 89 ]. Third, assembly of the mid-piece of the tail with tightly packed mitochondria to provide the ATPs necessary to support the flagellar movement of the sperm tails following the maturation of sperms in the epididymis [ 90 , 91 ]. The conventional concept is that these cytoskeletons are to be used for intracellular trafficking supported by corresponding actin- or MT-dependent plus ( +) or minus (-) end motor proteins.…”

Evaluation of Genistein as a Mitochondrial Modulator and Its Effects on Sperm Quality

“…Also, mitochondrial oxygen consumption is considered a central parameter of mitochondrial function and is positively correlated with sperm motility and vitality [ 15 ]. Thus, recent research in sperm physiology is focusing on this important organelle as a biomarker of sperm health and fertility [ 15 , 18 ].…”

“…These cells are sensitive to oxidation because they lack adequate repair mechanisms and possess inadequate antioxidant capacity. In contrast, at physiological concentrations, ROS trigger several important reproductive controls, such as sperm capacitation, hyperactivation, acrosome reaction, and oocyte fusion [ 18 ]. More recent studies are changing the dogma that ROS is a negative indicator of sperm function, indicating that ROS production may also reflect intense mitochondrial activity, leading to increased sperm function [ 15 , 18 ].…”

“…Mitochondria are key organelles in crucial sperm functions, such as motility, hyperactivation, capacitation, acrosome reaction, and fertilization [ 13 , 14 , 15 , 16 , 17 ]. Any structural or functional dysfunction of sperm mitochondria results in increased production of reactive oxygen species and decreased energy production, leading to sperm DNA damage and impaired sperm motility and semen parameters, consequently reducing male fertility [ 18 ]. Therefore, sperm mitochondrial functionality assessment is frequently used as an important screening tool for evaluating not only sperm quality but also the effects of various compounds, especially those with a hormone-like activity such as isoflavone [ 10 , 19 , 20 , 21 , 22 , 23 , 24 ].…”

Mitochondrial metabolism determines the functional status of human sperm and correlates with semen parameters

“…The source of ATP production for mammalian sperm motility has been widely studied ( Miki et al, 2004 ; Mukai and Okuno, 2004 ; Miki, 2007 ; Ruiz-Pesini et al, 2007 ; Ferramosca et al, 2008 , 2012 ; Goodson et al, 2012 ; Mukai and Travis, 2012 ; Piomboni et al, 2012 ; Moscatelli et al, 2017 ). The question of whether glycolysis or OXPHOS is the main source of ATP for sperm motility is controversial and considered species-specific ( Storey, 2008 ; Amaral et al, 2013 ; Castellini et al, 2021 ; Kumar, 2022 ). By inhibiting the glycolytic pathway and mitochondrial function, we were able to confirm that energy supply (ATP) formed at the mitochondrial level is important for sperm motility in semen samples with normal parameters.…”