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What are the main parts of the male reproductive system? What is the condition called that is failure of one or both of the testes to move from the Are there any similarities between male and female reproductive organs? Is it true that male has What are the functions of the epididymis and the seminal vesicles?
Which reproductive system is more complex, a man's or a woman's? If I were a sperm, what path would I take through the female reproductive system? What is the reproductive system? What is menstruation? Likewise, a remarkable change in human sperm mitochondria towards a more loosely wrapped morphology, possibly resulting from an increase in mitochondrial volume, was associated with capacitation a second maturation process usually occurring in the female reproductive tract and without which in vivo fertilisation is not possible; Vorup-Jensen et al.
These observations suggest that active sperm mitochondria are required for fertilisation. Nevertheless, it is important to note that, although mitochondria are present in the male gamete, paternal mtDNA is generally not transmitted to the embryo in mammalian intraspecific crosses. However, despite what is depicted in many scientific textbooks, the reason for this maternal-only mtDNA transmission is not that the sperm tail is discarded outside the oocyte at fertilisation but rather that paternal mitochondria are degraded inside the zygote, following penetration of the entire male gamete into the oocyte Ramalho-Santos Having said this, the time frame during which sperm mitochondria functionality is physiologically relevant and needs to be maintained comprises the period between epididymal storage, ejaculation, travelling between the female reproductive tract and sperm—oocyte interactions.
Any alteration in the mitochondrial genome, transcriptome, proteome or metabolome, or any cellular event resulting in compromised sperm mitochondrial functionality during this time may potentially affect sperm function, as will be discussed in detail Table 1.
Experimental evidence suggesting an association between mitochondrial functionality and sperm quality. First of all, defects in sperm mitochondrial ultrastructure seem to associate with decreased sperm motility in humans Mundy et al. At the molecular level, previous work has shown that deletions and other changes to mtDNA that influence cellular homoeostasis can result in reduced sperm functionality and male infertility, both in human patients for review see St John et al.
Likewise, microarray analysis suggested that sperm from asthenozoospermic samples have altered levels of specific mtRNAs, as well as of nuclear-encoded transcripts encoding mitochondrial proteins Jodar et al. However, and at least for some mtRNAs, this putative difference could not be corroborated by quantitative real-time PCR. In fact, comparative proteomic outcomes suggest that the expression of several sperm mitochondrial proteins may be altered in asthenozoospermic patients Zhao et al.
Furthermore, the activity of sperm mitochondrial enzymes, including ETC complexes, also correlates with sperm parameters, including concentration, vitality and motility Ruiz-Pesini et al.
In addition, the normalisation of other activities to citrate synthase often used as a marker for mitochondrial content suggested that the main explanation for these correlations might be mitochondrial volume, not distinct enzymatic activities in samples of varying quality Ruiz-Pesini et al.
Additionally, mice lacking the testis-specific form of cytochrome c also have impaired sperm function Narisawa et al. Furthermore, oxygen consumption in sperm mitochondria and mitochondrial respiratory efficiency also correlate with motility Stendardi et al.
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. In accordance with this notion, the same should be valid for mitochondrial parameters that depend on intact mitochondria, namely the MMP.
Interestingly, recent data suggest that the sperm motility of patients with abnormal sperm parameters can be enhanced by incubation with myoinositol, and this seems to be paralleled by an increase in the proportion of sperm with high MMP Condorelli et al. Finally, mitochondrial functionality may also be required for sperm capacitation.
To this extent, a peak in oxygen consumption was observed during in vitro capacitation and progesterone-induced acrosome reaction in bovine and boar sperm Cordoba et al.
In addition, it is well established that several sperm mitochondrial proteins undergo capacitation-dependent tyrosine phosphorylation for a review, see Shivaji et al. The preceding paragraphs seemingly stress that mitochondrial functionality is important for sperm activity, or, at the very least, that functional mitochondria help define a functional male gamete Table 1.
But what is exactly the role of mitochondria in sperm? Given that mitochondria are crucial for ATP production in eukaryotic cells and that ATP, in turn, is needed for sperm motility, the obvious answer would be to link these two events. However, the emerging portrait is much more complex, as will be discussed in the following section. In fact, the issue of sperm metabolism related to motility is the subject of an extensive debate Ramalho-Santos et al.
This hypothesis was first discussed in terms of compartmentalisation, namely that ATP produced in the midpiece would take too long to diffuse or shuttle along the flagellum, notably in species with longer sperm tails, such as rodents, although this notion is disputed Ford There are, however, several lines of evidence that seem to favour glycolysis as the main ATP source for sperm movement. Furthermore, male mouse knock-out models for the glycolysis-associated enzymes enolase 4 Nakamura et al.
However, recent data have shown that, at least for LDHC, the severity of the results depends on the mouse strain, with some strains relying more on glycolysis than others Odet et al. Using laser tweezers, it was also shown that human sperm motility was not dependent on MMP Nascimento et al. Therefore, it seems clear that there are contradictory data in the literature and that other metabolic pathways may be involved in sperm motility.
Recent data suggest that the use of endogenous substrates, including the oxidation of fatty acids Fig. Importantly, controlled ROS levels are needed for proper sperm function notably for motility, capacitation, the acrosome reaction, hyperactivation and fertilising ability , while ROS can also have a pathological effect on the male gamete, if in excess, or if there is an imbalance with available antioxidant defences, resulting in a decrease in viability, motility, MMP, and increases in DNA damage, morphology defects and lipid peroxidation, possibly resulting in apoptosis-like phenomena, as will be discussed below Kothari et al.
The recent development of specific probes for mitochondria-produced ROS mROS shows that excessive production results in membrane peroxidation and loss of motility Koppers et al. Additionally, a higher content of unsaturated fatty acid on sperm is also related to an increase in mROS again leading to motility loss and DNA damage Koppers et al.
Interestingly, mROS levels seem to vary in ejaculates, and when sperm are separated by Percoll gradients, the low-density fraction has a more prominent number of positive cells for mROS than the high-density fraction Koppers et al.
These results have suggested that both enzymatic and non-enzymatic antioxidants could be used to control the damage caused by excessive ROS levels in sperm, and there is some evidence that seems to consubstantiate this hypothesis, interestingly with antioxidants that specifically target mitochondria Lamond et al.
Although the capacity of mature sperm to carry out apoptosis has been questioned due to the paucity of cytoplasm, it is well known that human sperm can possess apoptotic markers and that this may influence sperm function and perhaps be involved in the removal of DNA-damaged sperm in the female reproductive tract Ramalho-Santos et al. It is worth mentioning that some studies note increases in sperm DNA damage as evidence for apoptosis, but, while DNA damage is certainly one of the main consequences of apoptosis, apoptosis may not be the only possible mechanism involved Sousa et al.
Although the extrinsic apoptotic pathway has been suggested to be active in sperm Sakkas et al. More general apoptosis hallmarks include the externalisation of phosphatidylserine PS to the outer leaflet of the plasma membrane and caspase activation. PS exposure can be monitored using fluorescent Annexin V in unpermeabilised live cells. In fact, Annexin V staining revealed more viable cells in normozoospermic patients Varum et al.
Importantly, the use of magnetic activated cell sorting MACS with Annexin V microbeads to select sperm reduced the percentage of altered cells Lee et al. On the other hand, the presence of activated caspases the final step in apoptosis has also been linked to poor sperm quality and lower fertilisation potential, possibly by affecting sperm DNA Weng et al. Interestingly, caspase activity seems to be focused in the sperm midpiece Weng et al.
An interconnection between capacitation and apoptosis signalling pathways has also been proposed Grunewald et al. Calcium signalling and calcium store mobilisation have recently been shown to be important in Assisted Reproductive Technologies ART success, as responses are clearly different when patients are compared with sperm donors Alasmari et al. However, what role sperm mitochondria have in this process is open to question, although sperm mitochondria are known to uptake calcium, and have been hinted as a possible intracellular calcium store in human sperm Costello et al.
In somatic cells, mitochondrial calcium uptake is undertaken by a mitochondrial calcium uniporter MCU; Fig. However, mitochondrial uncoupling does not seem to significantly affect the calcium oscillations occurring in either progesterone- or nitric oxide-stimulated human sperm Harper et al. Taken together, these data suggest that direct roles of mitochondrial calcium uptake in the control of intracellular calcium signals or in cell metabolism in mammalian sperm are unlikely.
Mitochondrial calcium signalling may be involved in the sperm intrinsic apoptotic pathway, but further studies are needed to better clarify this aspect. Although mitochondria functionality seems to be crucial for mammalian sperm, and while functional mitochondrial parameters clearly correlate with human sperm functionality and fertilisation ability, its exact role in the male gamete is not completely clear Fig. At any rate, it seems that the specific and evolutionarily conserved mitochondrial concentration at the sperm midpiece of all mammalian species studied so far does not currently contribute towards centralising ATP production for sperm movement, as is often assumed in many Cell Biology textbooks Alberts et al.
Thus, the role of mitochondria in sperm function might be predominantly related to other physiological aspects. To this extent, on the one hand, the controlled production of mROS balanced by effective antioxidant defences seems to be required for sperm motility, capacitation and fertilising ability.
This is especially relevant given the recent finding that the sperm chromatin may transfer acquired epigenetic states across generations Puri et al. The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the review. Given the extent of available literature, and the specific requirements of this review, readers have been referred to a few review articles. Apologies are due to all authors whose work was not directly cited.
J Saints is acknowledged for proofreading the manuscript. Molecular Human Reproduction 16 3 — Asian Journal of Andrology 13 36 — Asian Journal of Andrology 9 — Biology of Reproduction 87 Journal of Andrology 33 — Journal of Biological Chemistry — Andrology 1 — Human Reproduction 28 — New York: Garland Publishing. International Journal of Andrology 34 e — e Journal of Assisted Reproduction and Genetics 30 — International Journal of Andrology 33 e — e Human Reproduction 22 — Fertility and Sterility 96 — Molecular and Cellular Proteomics 12 — Nature Biochimica et Biophysica Acta — Invertebrate Biology 1 — 9.
International Review of Cell and Molecular Biology 1 — EMBO Reports 11 — Molecular Human Reproduction 10 — Journal of Proteome Research 8 — Urology 79 — Theriogenology 65 — Reproduction — Biology of Reproduction 82 — Biology of Reproduction 68 — Human Reproduction 24 —
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