Association of mutations in the zona pellucida binding protein 1 (ZPBP1) gene with abnormal sperm head morphology in infertile men

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.

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EFFECTS ON SPERM MORPHOLOGY BY ALLELES AT THE PINK-EYED DILUTION LOCUS IN MICE

Genetics ◽

10.1093/genetics/85.2.303 ◽

1977 ◽

Vol 85 (2) ◽

pp. 303-308

Author(s):

H Glenn Wolfe ◽

Robert P Erickson ◽

Linda C Schmidt

Keyword(s):

Gene Expression ◽

Sperm Morphology ◽

Sperm Head ◽

Male Sterile ◽

Abnormal Sperm ◽

Radiation Induced ◽

Allelic Interaction ◽

Head Morphology ◽

Pink Eyed Dilution ◽

Dark Pink

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.

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Inherited sperm head abnormalities in the B10.M mouse strain

Reproduction Fertility and Development ◽

10.1071/rd09295 ◽

2010 ◽

Vol 22 (7) ◽

pp. 1066 ◽

Cited By ~ 10

Author(s):

Hideo Gotoh

Keyword(s):

Functional Capacity ◽

High Frequency ◽

Segregation Analysis ◽

Inbred Mouse ◽

Sperm Head ◽

Mouse Strains ◽

Inbred Mouse Strains ◽

Abnormal Sperm ◽

Sperm Abnormality ◽

Head Morphology

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.

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Reproductive characteristics of the african pygmy hedgehog, atelerix albiventris

Reproduction ◽

10.1530/reprod/120.1.143 ◽

2000 ◽

pp. 143-150 ◽

Cited By ~ 8

Author(s):

JM Bedford ◽

OB Mock ◽

SK Nagdas ◽

VP Winfrey ◽

GE Olson

Keyword(s):

Fallopian Tube ◽

Zona Pellucida ◽

Sperm Head ◽

Reproductive Characteristics ◽

Cumulus Oophorus ◽

The Matrix ◽

Main Components ◽

Initial Binding ◽

Structural Matrix

To obtain further perspective on reproduction and particularly gamete function among so-called primitive mammals presently grouped in the Order Insectivora, we have examined the African hedgehog, Atelerix albiventris, in light of unusual features reported in shrews and moles. Atelerix proves to share many but not all of the characteristics seen in these other insectivores. The penis of Atelerix has a 'snail-like' form, but lacks the surface spines common in insectivores and a number of other mammals. Hedgehog spermatozoa display an eccentric insertion of the tail on the sperm head, and they manifest the barbs on the perforatorium that, in shrews, probably effect the initial binding of the sperm head to the zona pellucida. As a possible correlate, the structural matrix of the hedgehog acrosome comprises only two main components, as judged by immunoblotting, rather than the complex of peptides seen in the matrix of some higher mammals. The Fallopian tube of Atelerix is relatively simple; it displays only minor differences in width and in the arborized epithelium between the isthmus and ampulla, and shows no evidence of the unusual sperm crypts that characterize the isthmus or ampulla, depending on the species, in shrews and moles. In common with other insectivores, Atelerix appears to be an induced ovulator, as judged by the ovulation of some 6-8 eggs by about 23 h after injection of hCG. The dense cumulus oophorus appeared to have little matrix, in keeping with the modest dimensions of the tubal ampulla and, while it was not quite as discrete as that of soricids, it did show the same insensitivity to 0.5% (w/v) ovine or bovine hyaluronidase.

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The protein phosphatase with EF‐hand domain 1 is a calmodulin‐binding protein that interacts with proteins involved in sperm capacitation, binding to the zona pellucida, and motility

Molecular Reproduction and Development ◽

10.1002/mrd.23467 ◽

2021 ◽

Vol 88 (4) ◽

pp. 302-317

Author(s):

Camille Lavoie‐Ouellet ◽

Marie‐Ève Clark ◽

Juliana Ruiz ◽

Andrée‐Anne Saindon ◽

Pierre Leclerc

Keyword(s):

Zona Pellucida ◽

Protein Phosphatase ◽

Binding Protein ◽

Sperm Capacitation ◽

Calmodulin Binding ◽

Ef Hand

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Sperm surface hyaluronan binding protein (HABP1) interacts with zona pellucida of water buffalo (Bubalus bubalis) through its clustered mannose residues

Molecular Reproduction and Development ◽

10.1002/mrd.10207 ◽

2002 ◽

Vol 64 (2) ◽

pp. 235-244 ◽

Cited By ~ 12

Author(s):

Ilora Ghosh ◽

Kasturi Datta

Keyword(s):

Zona Pellucida ◽

Water Buffalo ◽

Binding Protein ◽

Bubalus Bubalis ◽

Sperm Surface ◽

Hyaluronan Binding

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Haploid male germ cells—the Grand Central Station of protein transport

Human Reproduction Update ◽

10.1093/humupd/dmaa004 ◽

2020 ◽

Vol 26 (4) ◽

pp. 474-500 ◽

Cited By ~ 4

Author(s):

Christiane Pleuger ◽

Mari S Lehti ◽

Jessica EM Dunleavy ◽

Daniela Fietz ◽

Moira K O’Bryan

Keyword(s):

Male Infertility ◽

Protein Transport ◽

Model System ◽

Sperm Head ◽

Vesicle Transport ◽

Future Research ◽

Significant Percentage ◽

Human Male ◽

Abnormal Sperm ◽

Haploid Male

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.

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How does sperm meet egg?--in a marsupial

Reproduction Fertility and Development ◽

10.1071/rd9940485 ◽

1994 ◽

Vol 6 (4) ◽

pp. 485 ◽

Cited By ~ 15

Author(s):

WG Breed

Keyword(s):

Acrosome Reaction ◽

Small Region ◽

Sperm Head ◽

Sminthopsis Crassicaudata ◽

Acrosomal Membrane ◽

Wide Range ◽

A Cell ◽

Inner Acrosomal Membrane ◽

Head Morphology ◽

Range Of Variation

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.

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231 SPERM SUBPOPULATIONS IN THE KOALA (PHASCOLARCTOS CINEREUS) EJACULATE

Reproduction Fertility and Development ◽

10.1071/rdv21n1ab231 ◽

2009 ◽

Vol 21 (1) ◽

pp. 213

Author(s):

N. Satake ◽

S. D. Johnston ◽

W. V. Holt

Keyword(s):

Sperm Motility ◽

Sperm Head ◽

Computer Assisted ◽

Multivariate Pattern Analysis ◽

Phascolarctos Cinereus ◽

Non Linear ◽

Group 3 ◽

Group 2 ◽

Head Morphology ◽

Multivariate Pattern

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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