Mitochondria, spermatogenesis and male infertility (original) (raw)
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Mitochondria functionality and sperm quality
Reproduction, 2013
Although mitochondria are best known for being the eukaryotic cell powerhouses, these organelles participate in various cellular functions besides ATP production, such as calcium homoeostasis, generation of reactive oxygen species (ROS), the intrinsic apoptotic pathway and steroid hormone biosynthesis. The aim of this review was to discuss the putative roles of mitochondria in mammalian sperm function and how they may relate to sperm quality and fertilisation ability, particularly in humans. Although paternal mitochondria are degraded inside the zygote, sperm mitochondrial functionality seems to be critical for fertilisation. Indeed, changes in mitochondrial integrity/functionality, namely defects in mitochondrial ultrastructure or in the mitochondrial genome, transcriptome or proteome, as well as low mitochondrial membrane potential or altered oxygen consumption, have been correlated with loss of sperm function (particularly with decreased motility). Results from genetically engine...
Mitochondrial Functionality in Male Fertility: From Spermatogenesis to Fertilization
Antioxidants
Mitochondria are structurally and functionally distinct organelles that produce adenosine triphosphate (ATP) through oxidative phosphorylation (OXPHOS), to provide energy to spermatozoa. They can also produce reactive oxidation species (ROS). While a moderate concentration of ROS is critical for tyrosine phosphorylation in cholesterol efflux, sperm–egg interaction, and fertilization, excessive ROS generation is associated with male infertility. Moreover, mitochondria participate in diverse processes ranging from spermatogenesis to fertilization to regulate male fertility. This review aimed to summarize the roles of mitochondria in male fertility depending on the sperm developmental stage (from male reproductive tract to female reproductive tract). Moreover, mitochondria are also involved in testosterone production, regulation of proton secretion into the lumen to maintain an acidic condition in the epididymis, and sperm DNA condensation during epididymal maturation. We also establis...
Mitochondria in Human Fertility and Infertility
International Journal of Molecular Sciences
In human spermatozoa and oocytes (and their surrounding granulosa cells), mitochondria carry out important functions relating to human fertility and infertility. Sperm mitochondria are not transmitted to the future embryo, but are closely related to the generation of energy needed for sperm movement, capacitation, and acrosome reactions, as well as for sperm–oocyte fusion. On the other hand, oocyte mitochondria produce energy required for oocyte meiotic division and their abnormalities can thus cause oocyte and embryo aneuploidy. In addition, they play a role in oocyte calcium metabolism and in essential epigenetic events during the oocyte-to-embryo transition. They are transmitted to the future embryos and may thus cause hereditary diseases in the offspring. Due to the long life span of the female germ cells, the accumulation of mitochondrial DNA abnormalities often causes ovarian aging. Mitochondrial substitution therapy is the only way of dealing with these issues nowadays. New t...
Male infertility and mitochondrial DNA
Biochemical and Biophysical Research Communications, 2004
The mitochondrial machinery plays a key role in the energy production and maintenance of spermatozoa motility. In this paper 200 idiopathic oligo-asthenozoospermic patients were classified on the basis of rapid progressive motility (''a'') and sperm concentration. Mitochondrial enzymatic activity was studied and correlated to the viability of sperm cells. Mitochondrial DNA purified from both motile and non-motile sperm of the same individuals was amplificated using PCR. Results suggested that only motile sperm have organelles functional in oxygen consumption, unequivocally demonstrating that motility depends on the mitochondrial activity. Mitochondrial DNA of oligo-asthenozoospermic patients seemed to present some defects that made DNA unavailable for amplification.
Antioxidants
The dogma of mitochondria as the major source of energy in supporting sperm motility should be critically reconsidered in the light of several experimental data pointing to a major role of glycolysis in mammalian spermatozoa. In this light, the reported positive correlation between the mitochondrial membrane potential (ΔΨm) and motility of ejaculated spermatozoa cannot be explained convincingly by an impaired mitochondrial ATP generation only. Evidence has been produced suggesting that, in human sperm, dysfunctional mitochondria represent the main site of generation of reactive oxygen species (ROS). Furthermore, in these organelles, a complex bidirectional relationship could exist between ROS generation and apoptosis-like events that synergize with oxidative stress in impairing sperm biological integrity and functions. Despite the activity of enzymatic and non-enzymatic antioxidant factors, human spermatozoa are particularly vulnerable to oxidative stress, which plays a major role i...
Zygote, 2018
SummaryDespite sperm mitochondrial relevance to the fertilization capacity, the processes involved in the production of ATP and functional dynamics of sperm mitochondria are not fully understood. One of these processes is the paradox involved between function and formation of reactive oxygen species performed by the organelle. Therefore, this review aimed to provide data on the role of sperm mitochondria in oxidative homeostasis and functionality as well the tools to assess sperm mitochondrial function.
Fertility and Sterility, 2006
By using flow-cytometric sorting, we compared some of the major factors related to fertility in sperm subpopulations with high and low mitochondrial membrane potential (⌬⌿ m ). Results demonstrate that ⌬⌿ m high spermatozoa represents a subpopulation of sperm with high fertility performance because they have normal morphology, high motility values, and calcium ionophore-induced acrosome reaction, suggesting the importance of mitochondrial functionality for fertilizing capacity of human spermatozoa. (Fertil Steril 2006;86: 1526 -30.
Fertility and Sterility, 2003
To evaluate the mitochondrial membrane potential (MMP) of spermatozoa and its correlation with semen parameters and production of reactive oxygen species (ROS) in infertile men and healthy donors. Design: Controlled prospective study. Setting: Male infertility clinic, Glickman Urological Institute, The Cleveland Clinic Foundation, Cleveland, Ohio. Patient(s): Nineteen infertile men and 7 healthy volunteers. Intervention(s): Standard semen analysis, assessment of MMP and ROS production in spermatozoa. The MMP was assessed by flow cytometry using the probe carbocyanine DiOC 6 (3) and ROS was measured with chemiluminescence assay using luminol. Main Outcome Measure(s): The results of MMP are reported as the median interquartile range (IQR) number of cells counted in different areas of fluorescence. Results of ROS measurement are expressed as ϫ10 6 counted photons per minute per 20 million sperm (cpm). Results: The patients with abnormal semen parameters had a significantly lower MMP [1337.7 (1066.38, 1879.2)], and higher ROS [1.12 (0.26, 3.86)] than the donors [MMP: 2482.9 (2162.5, 3520.6)] and [ROS: 0.10 (0.01, 0.14)]. The MMP was positively correlated with sperm concentration (r ϭ 0.62) and negatively correlated with the ROS produced (r ϭ Ϫ0.45). Conclusion(s): Measuring MMP in spermatozoa provides useful information about a man's fertility potential. Increased ROS production by spermatozoa is associated with a decreased MMP. (Fertil Steril 2003;80(Suppl 2):844 -50.
MITOCHONDRIAL DYSFUNCTION IN MALE SUB-FERTILITY: WHERE DO NUTRACEUTICALS STAND
Mitochondria plays a crucial role in male fertility by contributing to energy synthesis, meiosis, spermatogenesis, sperm maturation, and capacitation. Mitochondrial dysfunctions, in particular mitochondrial DNA (mtDNA) mutation, generation of reactive oxygen species (ROS), and lowered antioxidant capacity are associated with male sub-fertility. Under physiological conditions, sperms produce basal level of ROS necessary for sperm function. However, increased production of ROS causes DNA fragmentation and peroxidative damage to sperm plasma membrane, inducing cell death and causing a decline in fertility. Antioxidants could be employed to control the oxidative damage caused by excessive ROS during spermatogenesis. Mitochondrial medicine was introduced into clinical practice based on pathologies caused by abnormal functioning of mitochondria. Since then, various strategies have been implemented to develop mitochondrial therapeutics, including use of vitamins, co-factors, and antioxidants. The major supplementary antioxidants approved to manage male sub-fertility are L-carnitine, CoQ10, vitamin C, vitamin E, and Lycopene, as well as micronutrients such as folate and zinc. Evidence suggest favourable effects of nutraceutical-based antioxidant supplementation, alone or in combination, on sperm parameters such as sperm concentration, motility, and morphology. In this direction, future studies designed to precisely measure dosage, type, and duration of mitochondria-targeted treatments will encourage widespread use in clinical practices.
Mitochondria: participation to infertility as source of energy and cause of senescence
The international journal of biochemistry & cell biology, 2014
Mitochondria is a powerhouse organelle involved in ATP synthesis, calcium signaling, reactive oxygen species (ROS) by oxidative stress production, cell cycle arrest via apoptosis and sex steroid hormones biosynthesis. Improvement of sperm parameters such as motility, capacitation, acrosome reaction, and oocyte interaction, involve regulation of ROS levels by the mitochondria. In human, the relation between the quantitative level of mitochondrial DNA (mtDNA), oocyte cytoplasm maturation and fertilization potential, is not clear. It has been hypothesized that oocytes without sufficient wild type mtDNA and therefore able to generate ATP, would not normally be ovulated. This is reflected in the low numbers of mtDNA observed in degenerate oocytes obtained through super ovulation protocols during assisted reproductive technology programs. Different theories place mitochondria in a central role of oxidative damage to cells and tissues related to infertility declining and aging. Mitochondri...