CFAP43-mediated intra-manchette transport is required for sperm head shaping and flagella formation

Zygote ◽  
2020 ◽  
pp. 1-7
Author(s):  
Yi Yu ◽  
Jiaxiong Wang ◽  
Liming Zhou ◽  
Haibo Li ◽  
Bo Zheng ◽  
...  

Summary Mutation in CFAP43 leads to severe asthenozoospermia and multiple morphological abnormalities of the sperm flagellum (MMAF) in both human and mouse. Previous studies have shown that disruption of intra-manchette transport (IMT) caused failure of flagellum assembly and sperm head shaping. In a previous study, therefore, we postulated that disruption of IMT may contribute to the failure of sperm flagellum formation and result in MMAF, however the mechanisms underlying these defects are still poorly understood. Cfap43-deficient mice were studied here to reveal the cellular mechanisms of abnormal sperm head morphology and MMAF. Depletion of Cfap43 led to abnormal spermiogenesis and caused MMAF, sperm head abnormality and oligozoospermia. Furthermore, both abnormal manchette and disorganized ectoplasmic specialization (ES) could be observed at the elongated spermatids in Cfap43-deficient mice. Therefore, our findings demonstrated that, in mice, CFAP43-mediated IMT is essential for sperm head shaping and sperm flagellum formation.

1997 ◽  
Vol 12 (6) ◽  
pp. 1214-1217 ◽  
Author(s):  
I. Tasdemir ◽  
M. Tasdemir ◽  
S. Tavukcuoglu ◽  
S. Kahraman ◽  
K. Biberoglu

2011 ◽  
Vol 18 (1) ◽  
pp. 14-21 ◽  
Author(s):  
Alexander N. Yatsenko ◽  
Derek S. O'Neil ◽  
Angshumoy Roy ◽  
Paola A. Arias-Mendoza ◽  
Ruihong Chen ◽  
...  

2013 ◽  
Vol 114 (2) ◽  
pp. 92-102 ◽  
Author(s):  
S. Singh ◽  
L. Das Roy ◽  
Sarbani Giri

Metronidazole (MTZ) is a common antiparasitic and antibacterial drug. The drug and X-ray induced effects in mouse sperm count, sperm head abnormality and some oxidative stress parameters have been studied. Simultaneously the protective role of curcumin has been evaluated. MTZ, 40 mg/kg bw and 13.4 mg/kg bw × 3 days exposure induced abnormal sperm head and reduced total sperm count in Swiss albino mice both after 24 h and 35 days of exposure. However, MTZ treatment in mice receiving X-ray irradiation (0.5 Gy) did not changed the incidence of abnormal sperm population or decrease in the total sperm count. Hepatic glutathione (GSH), superoxide dismutase (SOD) declined significantly during the treatment phase with significant rise in lipid peroxidation of the tissue. The cellular changes were estimated by using lipid peroxidative indices like thiobarbituric acid reactive substances (TBARS). Elevated  TBARS is indicative of oxidative stress in treated mice. Furthermore, curcumin pre-treatment apparently reduced the frequency of sperm head abnormality and  TBARS induced by MTZ alone or in combination with X-ray and increased the levels of hepatic GSH and SOD. The additive effects of MTZ and X-ray could not be observed with regards to sperm head abnormality and total sperm count in the tested dose range although the cellular antioxidants were found to be significantly lowered and lipid peroxidantion increased. The possible role of MTZ and X-ray inducing sperm abnormality, decreased sperm count and alteration in GSH, SOD and TBARS and defensive role of curcumin have been evaluated.


Genetics ◽  
1977 ◽  
Vol 85 (2) ◽  
pp. 303-308
Author(s):  
H Glenn Wolfe ◽  
Robert P Erickson ◽  
Linda C Schmidt

ABSTRACT Sperm head morphology was analyzed in all genotypic combinations for alleles dark pink-eye (pd) and p-sterile alleles, p  6H, pbs (p-black-eyed sterile) and p  25H. Three of these, p  6H, pbs and p  25H, were radiation induced; homozygotes and heterozygotes of these three alleles are male sterile, whereas pd/— genotypes are fertile. Sperm heads were examined by light microscopy and assigned to one of five classes: A. normal and near-normal, B. triangulate and oblate, C. spatulate, D. elongate, and E. filamentous. Males of each sterile genotype had grossly abnormal sperm and each sterile genotype differed from all other sterile genotypes and from fertile genotypes in at least one class, except p  6H/p  6H compared to pbs/pbs. Frequency distribution profiles (1) revealed a complex pattern of allelic interaction and do not support a deletion-complementation hypothesis, (2) do not show simple bimodality, which might suggest post-meiotic (haploid) gene expression, and (3) together with unpublished breeding data, show that p  25H is not a remutation of p  6H.


2010 ◽  
Vol 22 (7) ◽  
pp. 1066 ◽  
Author(s):  
Hideo Gotoh

Examination of sperm head morphology is one of the requisite tests of the functional capacity of semen in reproduction. In the present study, genetic effects on morphological sperm head abnormalities in mice were investigated. The frequency of abnormal spermatozoa was determined in 17 inbred mouse strains and it was found that strain B10.M had the highest frequency of abnormal spermatozoa (44.7%). Segregation analysis was then used to show that the abnormal sperm phenotype in B10.M mice was inherited. The results indicated that this sperm abnormality was controlled by two distinct recessive alleles. It is proposed that the high frequency of the heritable abnormal sperm phenotype in the mouse B10.M strain explains the subfertility of this strain, as evidenced by its reduced litter size.


2020 ◽  
Vol 26 (4) ◽  
pp. 474-500 ◽  
Author(s):  
Christiane Pleuger ◽  
Mari S Lehti ◽  
Jessica EM Dunleavy ◽  
Daniela Fietz ◽  
Moira K O’Bryan

Abstract 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.


1994 ◽  
Vol 6 (4) ◽  
pp. 485 ◽  
Author(s):  
WG Breed

Australian marsupials exhibit a wide range of variation in sperm head morphology, and in thickness of the zona pellucida around the oocyte, suggesting interspecfic differences in the processes of sperm-egg interaction. The observations described here are largely based on the dasyurid Sminthopsis crassicaudata. They show that in oestrous females, after mating, a coagulum forms in the lateral vaginae and, within an hour of insemination, numerous spermatozoa congregate in the isthmus of the oviduct in which the vanguard population undergoes transformation with the head rotating on its axis with the tail to form a T-shape. Once oocytes are released, a few spermatozoa migrate to the higher reaches of the oviduct where sperm-zona binding occurs by way of the plasmalemma over the acrosomal region. The acrosome reaction takes place here and, as the egg rotates, the tail of the spermatozoon becomes parallel to the head. A small region of acrosome sometimes appears to remain intact at this time because spermatozoa with partly intact acrosomes have been found within the zona matrix. In some of these, electron-dense bridges between part of the inner and outer acrosomal membranes which may act as stabilizing structures, were also seen. The zona matrix is tightly packed around the penetrating spermatozoon, but that close to the acrosomal region becomes less electron-dense and more filamentous. Once incorporated into the egg, the spermatozoon lacks a cell membrane around the tail but vesicles close to the sperm head may, at least in part, be remnants of an inner acrosomal membrane. How generally applicable these observations are to other Australian marsupials remains to be determined.


Endocrinology ◽  
1999 ◽  
Vol 140 (11) ◽  
pp. 5348-5355 ◽  
Author(s):  
Sylvia L. Asa ◽  
Michele A. Kelly ◽  
David K. Grandy ◽  
Malcolm J. Low

Abstract Tuberoinfundibular dopamine tonically inhibits PRL expression and secretion from the pituitary gland by the activation of dopamine D2 receptors (D2R) localized on lactotrophs. Mutant female mice that lack D2Rs have persistent hyperprolactinemia but also develop extensive hyperplasia of pituitary lactotrophs and peliosis of the adenohypophysis at 9 to 12 months of age, while age-matched male D2R-deficient mice have no morphologic adenohypophysial lesion. We now report that both female and male D2R-deficient mice 17 to 20 months of age develop pituitary lactotroph adenomas. Of 12 aged female mice examined, all developed monohormonal PRL-immunoreactive neoplasms that had a characteristic juxtanuclear Golgi pattern of PRL staining and loss of the reticulin fiber network. Several of these adenomas were 50-fold larger than normal glands with marked suprasellar extension and invasion of brain but no gross evidence of distant metastases. They also had striking peliosis that was more marked than the lesion seen in the hyperplastic pituitaries of the younger females. These findings demonstrate that a chronic loss of neurohormonal dopamine inhibition promotes the hyperplasia-neoplasia sequence in adenohypophysial lactotrophs. Our results are analogous to previous data indicating that protracted stimulation of adenohypophysial cells by hormones or growth factors results in proliferation with initial hyperplasia followed by the development of neoplasia. Six aged male D2R-deficient mice had slightly enlarged anterior pituitaries similar in size to normal female glands. However, each case exhibited multifocal, microscopic lactotroph adenomas with strong nuclear immunoreactivity for estrogen receptors and Pit-1 transcription factor. The unexpected development of adenomas in males without preexisting or concomitant hyperplasia suggests that prolonged loss of dopamine inhibition may also cause neoplasia by distinct cellular mechanisms in male and female animals.


2018 ◽  
Vol 102 (4) ◽  
pp. 636-648 ◽  
Author(s):  
Frederick N. Dong ◽  
Amir Amiri-Yekta ◽  
Guillaume Martinez ◽  
Antoine Saut ◽  
Julie Tek ◽  
...  

2009 ◽  
Vol 21 (1) ◽  
pp. 213
Author(s):  
N. Satake ◽  
S. D. Johnston ◽  
W. V. Holt

Koala semen contains a heterogeneous mixture of sperm morphotypes, mainly attributable to extreme degree of shape variability displayed by the hooked sperm head. By analogy with other species, we anticipate that the morphotypes may exhibit correspondingly different sperm-motility behaviors, largely caused by the differences in hydrodynamic interactions with the suspending media. This trend has been shown in human spermatozoa where motility behavior was demonstrably correlated with the sperm head morphology (Overstreet et al. 1981). In this study, we have investigated the heterogeneity of koala sperm motility profiles in semen in an effort to determine whether distinct sperm subpopulations within ejaculates are recognizable by the use of computer-assisted sperm motility analysis. Ejaculates from 5 males were collected by electroejaculation, then diluted and transported in Tris-citrate-glucose (TCG) diluent. Spermatozoa were washed through a 35–60% Percoll gradient to separate seminal plasma and the majority of the prostatic bodies from spermatozoa. Spermatozoa from the washed pellet were then diluted in TCG at 35°C, incubated for 10 min, and video recorded using a negative phase ×10 objective. Sperm motion parameters were then analyzed using the Hobson sperm tracker (Hobson Vision Systems, UK: Holt et al. 1996 J. Androl. 17, 587–596). Multivariate pattern analysis (PATN; CSIRO Australia; Abaigar 1999 Biol. Reprod. 60, 32–41) was used to distinguish 3 sperm subgroups, consistently shown in each ejaculate, within the data (1936 tracks × 6 kinetic parameters; VCL, VAP, MAD, BCF, ALH, LIN). After group allocation by PATN, all parameters showed significant differences between each of the groups (P < 0.0001). Group 1, approximately 25% of the sperm tracks, showed profiles of spermatozoa with fast, non-linear motility (VCL 106.88 ± 28.15; BCF 3.23 ± 3.81; LIN 14.08 ± 10.20). Group 2, approximately 27% of sperm tracks, showed profiles of fast, linear motility (VCL 63.92 ± 13.50; BCF 7.90 ± 3.42; LIN 28.10 ± 12.15). Group 3, 48% of sperm tracks, showed profiles of slow, non-linear or circular patterns of motility (VCL 39.05 ± 11.92; BCF 0.02 ± 0.35; LIN 5.15 ± 4.88). The recognition of 3 clearly identifiable subgroups supports our hypothesis that heterogeneity of sperm motility patterns exists within koala ejaculates. These may be a reflection of the heterogeneity in sperm-head morphotypes in koala semen, but that remains to be investigated in more detail. The clear distinctions between these groups, and the observation that all 3 subpopulations exist in each of the ejaculates, also suggest that the spermatozoa exhibit functional differences, possibly related to biochemical or maturational status. Many thanks to Dr. Michael Pyne and Dr. Vere Nicholson and their teams and animals at Currumbin Wildlife Sanctutary and Dreamwolrd QLD for all their help and support for the collection of samples.


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