Mitochondria: their role in spermatozoa and in male infertility

Abstract

BACKGROUND The best-known role of spermatozoa is to fertilize the oocyte and to transmit the paternal genome to offspring. These highly specialized cells have a unique structure consisting of all the elements absolutely necessary to each stage of fertilization and to embryonic development. Mature spermatozoa are made up of a head with the nucleus, a neck, and a flagellum that allows motility and that contains a midpiece with a mitochondrial helix. Mitochondria are central to cellular energy production but they also have various other functions. Although mitochondria are recognized as essential to spermatozoa, their exact pathophysiological role and their functioning are complex. Available literature relative to mitochondria in spermatozoa is dense and contradictory in some cases. Furthermore, mitochondria are only indirectly involved in cytoplasmic heredity as their DNA, the paternal mitochondrial DNA, is not transmitted to descendants. OBJECTIVE AND RATIONAL This review aims to summarize available literature on mitochondria in spermatozoa, and, in particular, that with respect to humans, with the perspective of better understanding the anomalies that could be implicated in male infertility. SEARCH METHODS PubMed was used to search the MEDLINE database for peer-reviewed original articles and reviews pertaining to human spermatozoa and mitochondria. Searches were performed using keywords belonging to three groups: ‘mitochondria’ or ‘mitochondrial DNA’, ‘spermatozoa’ or ‘sperm’ and ‘reactive oxygen species’ or ‘calcium’ or ‘apoptosis’ or signaling pathways’. These keywords were combined with other relevant search phrases. References from these articles were used to obtain additional articles. OUTCOMES Mitochondria are central to the metabolism of spermatozoa and they are implicated in energy production, redox equilibrium and calcium regulation, as well as apoptotic pathways, all of which are necessary for flagellar motility, capacitation, acrosome reaction and gametic fusion. In numerous cases, alterations in one of the aforementioned functions could be linked to a decline in sperm quality and/or infertility. The link between the mitochondrial genome and the quality of spermatozoa appears to be more complex. Although the quantity of mtDNA, and the existence of large-scale deletions therein, are inversely correlated to sperm quality, the effects of mutations seem to be heterogeneous and particularly related to their pathogenicity. WIDER IMPLICATIONS The importance of the role of mitochondria in reproduction, and particularly in gamete quality, has recently emerged following numerous publications. Better understanding of male infertility is of great interest in the current context where a significant decline in sperm quality has been observed.

Mitochondrial Dynamics Markers and Related Signaling Molecules Are Important Regulators of Spermatozoa Number and Functionality

“…The methods used in this study were carried out in accordance with the relevant guidelines and regulations. These methods were previously reported by our group (for all references please see [ 13 , 14 , 46 ]) and are outlined briefly here, but more details are available in Supplementary Materials .…”

“…Three-months-old male Wistar rats were used for the experiments. Model of psychophysical stress by immobilization (IMO) was performed in the morning by the method previously described [ 13 , 14 , 46 ]. Briefly, animals were divided into the following groups: control—unstressed rats; 1×3hIMO—rats subjected to IMO once, for 3 h; 10×3hIMO—rats subjected to repeat IMO of 3 h for 10 consecutive days.…”

“…More importantly, all signaling pathways regulating mitochondrial dynamics are essentially involved in the regulation of spermatozoa function. The recent review article pointed out the great gap and interest in the research related to mitochondria and male fertility [ 46 ]. Many studies discussed the correlation between stress and/or stressful life and male (in)fertility [ 3 ].…”

Potential of Mitochondrial Genome Editing for Human Fertility Health

“…The deletion of 4,977 bp has been frequently reported to be associated with modified sperm motility and sperm count (Namaghi and Vaziri, 2017, Gholinezhad et al, 2019, Wu et al, 2019, Al Zoubi et al, 2020. Other deletions, multiple deletions in particular, have also been shown to be more frequently found in sperm from infertile patients (Boguenet et al, 2021). According to studies on sperm fractions obtained from density gradient analysis, normal spermatozoa are found in high-density fractions containing more wild-type mtDNA (O'Connell et al, 2003).…”

“…Generally, male reproductive function seems particularly vulnerable to mitochondrial dysfunction associated with mtDNA abnormalities ( Vaught and Dowling, 2018 ). Defects in sperm ETC functioning have been proven to be associated with sperm quality impairment ( Boguenet et al, 2021 ). In this respect, oxygen consumption and mitochondrial respiration efficiency are correlated with sperm motility ( Sousa et al, 2011 ; Ferramosca et al, 2012 ).…”