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Human Reproduction Update Jun 2020The precise movement of proteins and vesicles is an essential ability for all eukaryotic cells. Nowhere is this more evident than during the remarkable transformation... (Review)
Review
BACKGROUND
The precise movement of proteins and vesicles is an essential ability for all eukaryotic cells. Nowhere is this more evident than during the remarkable transformation that occurs in spermiogenesis-the transformation of haploid round spermatids into sperm. These transformations are critically dependent upon both the microtubule and the actin cytoskeleton, and defects in these processes are thought to underpin a significant percentage of human male infertility.
OBJECTIVE AND RATIONALE
This review is aimed at summarising and synthesising the current state of knowledge around protein/vesicle transport during haploid male germ cell development and identifying knowledge gaps and challenges for future research. To achieve this, we summarise the key discoveries related to protein transport using the mouse as a model system. Where relevant, we anchored these insights to knowledge in the field of human spermiogenesis and the causality of human male infertility.
SEARCH METHODS
Relevant studies published in English were identified using PubMed using a range of search terms related to the core focus of the review-protein/vesicle transport, intra-flagellar transport, intra-manchette transport, Golgi, acrosome, manchette, axoneme, outer dense fibres and fibrous sheath. Searches were not restricted to a particular time frame or species although the emphasis within the review is on mammalian spermiogenesis.
OUTCOMES
Spermiogenesis is the final phase of sperm development. It results in the transformation of a round cell into a highly polarised sperm with the capacity for fertility. It is critically dependent on the cytoskeleton and its ability to transport protein complexes and vesicles over long distances and often between distinct cytoplasmic compartments. The development of the acrosome covering the sperm head, the sperm tail within the ciliary lobe, the manchette and its role in sperm head shaping and protein transport into the tail, and the assembly of mitochondria into the mid-piece of sperm, may all be viewed as a series of overlapping and interconnected train tracks. Defects in this redistribution network lead to male infertility characterised by abnormal sperm morphology (teratozoospermia) and/or abnormal sperm motility (asthenozoospermia) and are likely to be causal of, or contribute to, a significant percentage of human male infertility.
WIDER IMPLICATIONS
A greater understanding of the mechanisms of protein transport in spermiogenesis offers the potential to precisely diagnose cases of male infertility and to forecast implications for children conceived using gametes containing these mutations. The manipulation of these processes will offer opportunities for male-based contraceptive development. Further, as increasingly evidenced in the literature, we believe that the continuous and spatiotemporally restrained nature of spermiogenesis provides an outstanding model system to identify, and de-code, cytoskeletal elements and transport mechanisms of relevance to multiple tissues.
Topics: Animals; Haploidy; Humans; Infertility, Male; Male; Mice; Microtubules; Protein Transport; Spermatids; Spermatogenesis; Spermatozoa
PubMed: 32318721
DOI: 10.1093/humupd/dmaa004 -
Anatomia, Histologia, Embryologia Nov 2020The black marsh turtle (Geoemydidae: Siebenrockiella crassicollis) is a freshwater turtle that occurs in equatorial tropical climates in South East Asia. The semen of S....
The black marsh turtle (Geoemydidae: Siebenrockiella crassicollis) is a freshwater turtle that occurs in equatorial tropical climates in South East Asia. The semen of S. crassicollis was investigated by electroejaculation. The spermatozoa of S. crassicollis are filiform in shape with curved heads. The entire length, midpiece to tail length, tail width and tail length of the spermatozoa were 71.33 ± 1.55 μm, 49.92 ± 1.13 μm, 0.43 ± 0.02 μm and 48.53 ± 0.25 μm, respectively. The head length, head width across the middle and head width across the base were 14.00 ± 0.38 μm, 0.79 ± 0.03 μm and 0.91 ±0.0.03 μm, respectively. The acrosomal region of the S. crassicollis spermatozoa was narrower than the head, with an acrosomal length and width at the annulus of 2.90 ± 0.13 μm and 0.43 ± 0.01 μm, respectively. The midpiece of the S. crassicollis spermatozoa was narrower than the head and contained 30-40 mitochondrial balls, each with a ball diameter of 0.16 ± 0.002 μm. The midpiece length, midpiece width and tail length were 4.92 ± 0.16, 0.78 ± 0.03 and 48.53 ± 0.25 μm, respectively. This study presents the characteristic appearance of a freshwater turtle spermatozoa in Southeast Asia, as observed under an electron microscope. The spermatozoa of Siebenrockiella crassicollis are morphologically different from those of other freshwater turtles from other regions described in previous studies.
Topics: Anesthesia; Anesthetics, Dissociative; Animals; Asia, Southeastern; Ejaculation; Electric Stimulation; Fresh Water; Ketamine; Male; Microscopy, Electron, Scanning; Spermatozoa; Tropical Climate; Turtles
PubMed: 32686185
DOI: 10.1111/ahe.12592 -
Animal Reproduction Science Mar 2021The C-terminal kinesin motor protein (KIFC1) has essential functions in spermatogenesis. To evaluate molecular mechanisms of KIFC1 during teleost fish spermatogenesis,...
The C-terminal kinesin motor protein (KIFC1) has essential functions in spermatogenesis. To evaluate molecular mechanisms of KIFC1 during teleost fish spermatogenesis, there was cloning and sequencing the kifc1 cDNA in the testis of Larimichthys polyactis. Quantitative PCR results indicated there were Lp-kifc1 mRNA transcripts in the testes. Results from conducting fluorescence in situ hybridization and immunofluorescence procedures indicated there were trends in relative abundance changes in Lp-kifc1 mRNA transcripts that were associated with abundance of Lp-KIFC1 protein during spermatogenesis. The Lp-KIFC1 protein was detected at all stages of spermatogenesis. There was minimal Lp-KIFC1 in the cytoplasm of spermatogonia, with content being greater and concentrated in the perinuclear region in spermatocytes and during early/mid-stages of development of spermatids. There were large abundances of Lp-KIFC1 in spermatids at the mid-developmental stage. In late-developing spermatids, Lp-KIFC1 content was less and concentrated in the bottom of the nucleus, where the midpiece formed. There was a small Lp-KIFC1 in the midpiece of mature sperm. These findings indicate Lp-KIFC1 may have functions in L. polyactis spermatogenesis. Results from conducting immunofluorescence procedures indicated Lp-KIFC1 was co-localized microtubules and mitochondria throughout spermatogenesis. There were large abundances of Lp-KIFC1 and tubulin in spermatids during the mid-developmental stage, when there is a decrease in size and reshaping of the nucleus. During midpiece formation, there was co-localization of the Lp-KIFC1 and mitochondria in the spermatid perinuclear region to the midpiece. These findings indicate Lp-KIFC1 is involved in nuclear reshaping and midpiece formation during spermatogenesis in L. polyactis.
Topics: Amino Acid Sequence; Animals; Cell Nucleus; Cloning, Molecular; DNA, Complementary; Fishes; Gene Expression Regulation; Kinesins; Male; Microtubules; Mitochondria; Phylogeny; Protein Conformation; Protein Transport; RNA, Messenger; Spermatogenesis; Spermatozoa; Testis; Tubulin
PubMed: 33581918
DOI: 10.1016/j.anireprosci.2021.106702 -
Molecular and Cellular Endocrinology Jun 2018Mammalian fertilization relies on sperm finding the egg and penetrating the egg vestments. All steps in a sperm's lifetime crucially rely on changes in the second... (Review)
Review
Mammalian fertilization relies on sperm finding the egg and penetrating the egg vestments. All steps in a sperm's lifetime crucially rely on changes in the second messenger cAMP (cyclic adenosine monophosphate). In recent years, it has become clear that signal transduction in sperm is not a continuum, but rather organized in subcellular domains, e.g. the sperm head and the sperm flagellum, with the latter being further separated into the midpiece, principal piece, and endpiece. To understand the underlying signaling pathways controlling sperm function in more detail, experimental approaches are needed that allow to study sperm signaling with spatial and temporal precision. Here, we will give a comprehensive overview on cAMP signaling in mammalian sperm, describing the molecular players involved in these pathways and the sperm functions that are controlled by cAMP. Furthermore, we will highlight recent advances in analyzing and manipulating sperm signaling with spatio-temporal precision using light.
Topics: Animals; Cyclic AMP; Light; Male; Mammals; Optogenetics; Signal Transduction; Spermatozoa
PubMed: 29146556
DOI: 10.1016/j.mce.2017.11.008 -
Mitochondrial DNA. Part A, DNA Mapping,... May 2021The tenets underlying the use of mtDNA in phylogenetic and systematic analyses are strict maternal inheritance, clonality, homoplasmy, and difference due to mutation:... (Review)
Review
The tenets underlying the use of mtDNA in phylogenetic and systematic analyses are strict maternal inheritance, clonality, homoplasmy, and difference due to mutation: that is, there are species-specific mtDNA sequences and phylogenetic reconstruction is a matter of comparing these sequences and inferring closeness of relatedness from the degree of sequence similarity. Yet, how mtDNA behavior became so defined is mysterious. Even though early studies of fertilization demonstrated for most animals that not only the head, but the sperm's tail and mitochondria-bearing midpiece penetrate the egg, the opposite - only the head enters the egg - became fact, and mtDNA conceived as maternally transmitted. When midpiece/tail penetration was realized as true, the conceptions 'strict maternal inheritance', etc., and their application to evolutionary endeavors, did not change. Yet there is mounting evidence of paternal mtDNA transmission, paternal and maternal combination, intracellular recombination, and intra- and intercellular heteroplasmy. Clearly, these phenomena impact the systematic and phylogenetic analysis of mtDNA sequences.
Topics: DNA, Mitochondrial; Evolution, Molecular; Genome, Mitochondrial; Mitochondria; Phylogeny
PubMed: 33818247
DOI: 10.1080/24701394.2021.1899165 -
Conservation Physiology 2023Managing a species of conservation concern can be best achieved when there is information on the reproductive physiology of both sexes available; however, many species...
Managing a species of conservation concern can be best achieved when there is information on the reproductive physiology of both sexes available; however, many species lack this critical, baseline information. One such species, the tuatara (), is the last surviving member of one of the four reptile orders (Rhynchocephalia) and is the only reptile known to lack a male intromittent organ. Culturally and evolutionarily significant, the conservation of this species is a global priority for the maintenance of biodiversity. In light of this, we characterized the morphology, viability and swim speed of mature tuatara sperm for the first time. We found that tuatara sperm are filiform and bear the remarkably conserved three-part sperm structure seen across the animal kingdom. Tuatara sperm are long (mean total length 166 μm), with an approximate head:midpiece:tail ratio of 15:1:17. While tuatara sperm are capable of high levels of within-mating viability (94.53%), the mean viability across all samples was 58.80%. Finally, tuatara sperm had a mean curvilinear velocity swim speed (μ × s - 1) of 82.28. At the population level, there were no differences in viability or mean swim speed between sperm collected from a male's first mating of a season and repeat matings; however, the maximum sperm swim speed increased in observed repeated matings relative to first matings. Interestingly, faster sperm samples had shorter midpieces, but had greater viability and longer head and tail sections. This work expands our understanding of male reproductive characteristics and their variation to a new order, provides wild references for the assessment of captive individuals, lays the groundwork for potential assisted reproductive techniques and highlights variation in male reproductive potential as an important factor for consideration in future conservation programs for this unique species.
PubMed: 37663926
DOI: 10.1093/conphys/coad071 -
Animals : An Open Access Journal From... Jul 2023Sperm morphology can predict the reproductive male fertilizing potential. This study aimed to determine the morphological and morphometric spermatozoa characteristics...
Sperm morphology can predict the reproductive male fertilizing potential. This study aimed to determine the morphological and morphometric spermatozoa characteristics from guinea pigs subjected to different photoperiodic stimulation. Thirty F1 guinea pigs were randomly assigned to three photoperiodic treatments: FT1 (photoperiod with 10 Light/14 Dark LED light), FT2 (photoperiod with 10L/14D sunlight), and FT0 (room without direct light source). At 107 ± 9.8 days of age, sperm concentration and motility were higher in the FT0 and FT1 groups ( < 0.05); furthermore, there were no differences in nucleus length and ellipticity between the FT0 and FT1 groups, but the sperm of the FT1 group was higher in perimeter and nuclear area, while that of the FT0 group was higher in roughness, regularity, midpiece length, and tail ( < 0.01). Expanding acrosome (Type 2) was more frequent in the FT2 group, but there was variation in head measurements between all morphological categories. Pregnancy rate, calving age, and mating age were higher in the FT0 group; meanwhile, the FT1 group initiated successful matings earlier ( < 0.01). The FT0 group had a higher fertility rate, and the age of mating and first calving were earlier in the FT1 group than the FT0 group, but no pregnancies were reported for the FT2 group. Photoperiodic stimulation can increase the morphometric dimensions of guinea pig spermatozoa, favoring the reproductive characteristics, but sunlight could reduce their size due to heat stress.
PubMed: 37508028
DOI: 10.3390/ani13142249 -
ELife Apr 2023The manchette is a transient and unique structure present in elongating spermatids and required for proper differentiation of the germ cells during spermatogenesis....
The manchette is a transient and unique structure present in elongating spermatids and required for proper differentiation of the germ cells during spermatogenesis. Previous work indicated that the MEIG1/PACRG complex locates in the manchette and is involved in the transport of cargos, such as SPAG16L, to build the sperm flagellum. Here, using co-immunoprecipitation and pull-down approaches in various cell systems, we established that DNALI1, an axonemal component originally cloned from , recruits and stabilizes PACRG and we confirm in vivo, the co-localization of DNALI1 and PACRG in the manchette by immunofluorescence of elongating murine spermatids. We next generated mice with a specific deficiency of DNALI1 in male germ cells, and observed a dramatic reduction of the sperm cells, which results in male infertility. In addition, we observed that the majority of the sperm cells exhibited abnormal morphology including misshapen heads, bent tails, enlarged midpiece, discontinuous accessory structure, emphasizing the importance of DNALI1 in sperm differentiation. Examination of testis histology confirmed impaired spermiogenesis in the mutant mice. Importantly, while testicular levels of MEIG1, PACRG, and SPAG16L proteins were unchanged in the mutant mice, their localization within the manchette was greatly affected, indicating that DNALI1 is required for the formation of the MEIG1/PACRG complex within the manchette. Interestingly, in contrast to MEIG1 and PACRG-deficient mice, the DNALI1-deficient mice also showed impaired sperm spermiation/individualization, suggesting additional functions beyond its involvement in the manchette structure. Overall, our work identifies DNALI1 as a protein required for sperm development.
Topics: Male; Mice; Animals; Sperm Tail; Seeds; Spermatogenesis; Proteins; Spermatids; Testis; Nuclear Proteins; Phosphoproteins; Cell Cycle Proteins
PubMed: 37083624
DOI: 10.7554/eLife.79620 -
Antioxidants (Basel, Switzerland) Jan 2021Besides ATP production, mitochondria are key organelles in several cellular functions, such as steroid hormone biosynthesis, calcium homoeostasis, intrinsic apoptotic... (Review)
Review
Besides ATP production, mitochondria are key organelles in several cellular functions, such as steroid hormone biosynthesis, calcium homoeostasis, intrinsic apoptotic pathway, and the generation of reactive oxygen species (ROS). Despite the loss of the majority of the cytoplasm occurring during spermiogenesis, mammalian sperm preserves a number of mitochondria that rearrange in a tubular structure at the level of the sperm flagellum midpiece. Although sperm mitochondria are destroyed inside the zygote, the integrity and the functionality of these organelles seem to be critical for fertilization and embryo development. The aim of this review was to discuss the impact of mitochondria-produced ROS at multiple levels in sperm: the genome, proteome, lipidome, epigenome. How diet, aging and environmental pollution may affect sperm quality and offspring health-by exacerbating oxidative stress-will be also described.
PubMed: 33440836
DOI: 10.3390/antiox10010092 -
Animal Reproduction Science May 2015Computer-assisted sperm morphometry analysis (CASMA or ASMA) systems were developed to reduce the subjectivity of sperm morphology assessement. This review focuses on a... (Review)
Review
Computer-assisted sperm morphometry analysis (CASMA or ASMA) systems were developed to reduce the subjectivity of sperm morphology assessement. This review focuses on a complete description of the CASMA technique, including recent developments, factors of variation, results in the different species and possible applications. Techniques to study sperm morphometry include light microscopy, phase-contrast microscopy and, more recently, fluorescence microscopy. Most published studies on sperm morphometry have been centered on the whole sperm heads, although some of them also measured other parts of the sperm structure, such as the nucleus, acrosome, midpiece or flagellum. The independent study of sperm components may be more informative than the traditional assessment of the whole sperm head. Morphometric data provided by the CASMA system may be analyzed using classical statistics although, given the heterogeneity of spermatozoa in the ejaculates, the study of sperm subpopulations using clustering procedures may be more informative. Morphometric results may vary depending on factors intrinsic and extrinsic to the semen donor. Intrinsic factors may include, among others, genetic factors, age and sexual maturity. Extrinsic factors may include those related to the influence of environment on the donor, as well as those related with sample processing and the morphometric analysis itself. Once standardized, this technique may provide relevant information in studies focused on evolutionary biology, sperm formation, sperm quality assessment, including prediction of the potential fertility, semen cryopreservation, or the effect of reprotoxicants.
Topics: Animals; Image Processing, Computer-Assisted; Male; Mammals; Semen Analysis; Spermatozoa
PubMed: 25802026
DOI: 10.1016/j.anireprosci.2015.03.002