Lack of a head in human spermatozoa from sterile patients: a syndrome associated with impaired fertilization

Chemes, H; Carizza, C.; Scarinci, F.; Brugo, S.; Neuspiller, Nicolás; Schwarsztein, Luis

doi:10.1016/s0015-0282(16)50011-9

Cited by 86 publications

(11 citation statements)

References 11 publications

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“…However, Odf2-DDS could be found in the future, as infertility due to asthenoteratozoospermia is reported to be mainly caused by impaired development of the outer dense fibres 46 , and as the amino acid sequences of human and mouse ODF2 are almost identical 47 . In addition, three patients, whose conditions were thought to be of genetic origin, contained numerous motile acephalic sperm (headless tails) 35 as shown in this study, in which headless tails as well as tail-less head were abundant. Patients with severe infertility due to Odf2 haploinsufficiency can survive to adulthood and will be diagnosed with a type of teratozoospermia.…”

Section: Discussionsupporting

confidence: 55%

Odf2 haploinsufficiency causes a new type of decapitated and decaudated spermatozoa, Odf2-DDS, in mice

Ito

Akutsu

Yao

et al. 2019

Sci Rep

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Outer dense fibre 2 (Odf2 or ODF2) is a cytoskeletal protein required for flagella (tail)-beating and stability to transport sperm cells from testes to the eggs. There are infertile males, including human patients, who have a high percentage of decapitated and decaudated spermatozoa (DDS), whose semen contains abnormal spermatozoa with tailless heads and headless tails due to head-neck separation. DDS is untreatable in reproductive medicine. We report for the first time a new type of Odf2-DDS in heterozygous mutant Odf2+/− mice. Odf2+/− males were infertile due to haploinsufficiency caused by heterozygous deletion of the Odf2 gene, encoding the Odf2 proteins. Odf2 haploinsufficiency induced sperm neck-midpiece separation, a new type of head-tail separation, leading to the generation of headneck sperm cells or headnecks composed of heads with necks and neckless tails composed of only the main parts of tails. The headnecks were immotile but alive and capable of producing offspring by intracytoplasmic headneck sperm injection (ICSI). The neckless tails were motile and could induce capacitation but had no significant forward motility. Further studies are necessary to show that ICSI in humans, using headneck sperm cells, is viable and could be an alternative for infertile patients suffering from Odf2-DDS.

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Section: Discussionsupporting

confidence: 55%

Odf2 haploinsufficiency causes a new type of decapitated and decaudated spermatozoa, Odf2-DDS, in mice

Ito

Akutsu

Yao

et al. 2019

Sci Rep

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“…Formation of HTCA and sperm tail requires many proteins that are presumably transported by a transient microtubular structure, the manchette 24,27 . The HTCA is essential for functional sperm, and its malformation causes acephalic spermatozoa and male infertility due to fragile attachment of sperm head and tail or even detachment 12,46 . Albeit essential for fertilisation, the knowledge of the molecular composition of the HTCA is just in the beginning.…”

Section: Discussionmentioning

confidence: 99%

The WD40-protein CFAP52/WDR16 is a centrosome/basal body protein and localizes to the manchette and the flagellum in male germ cells

Contreras

Hoyer‐Fender

2020

Sci Rep

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Development of spermatozoa requires remodelling and formation of particular structures. In elongating spermatids, the transient microtubular manchette contributes to the formation of the head-tail coupling apparatus (HTCA) and the sperm tail. The HTCA derives from the centrosome in that the proximal centriole inserts into the nuclear indentation and the distal centriole gives rise to the sperm flagellum. Although impairments in the formation of HTCA and sperm tail cause male infertility their molecular constituents are only partially known. The WD40-protein CFAP52 is implicated in motile cilia, but its relevance for male germ cell differentiation is not known. Here we show that CFAP52 is widespread expressed and localizes to a subset of microtubular structures. In male germ cells, CFAP52 is a component of the transient manchette and the sperm tail. However, expression of Cfap52 is not restricted to motile cilia-bearing cells. In NIH3T3 cells, CFAP52 localizes to the centrosome, the basal body, and the mitotic spindle poles, but not to the primary cilium. Our results demonstrate that CFAP52 is not restricted to motile cilia but instead most likely functions in constituting the centrosome/basal body matrix and the sperm tail. The cilia and flagella associated protein 52, CFAP52 (also named WDR16, WD repeat domain 16, WDRPUH, FLJ37528) is a member of the large WD40-repeat protein family and is widely expressed in eukaryotes. WD40repeats, which are also known as WD or beta-transducin repeats, are short motifs of 40-60 amino acids often terminating in the dipeptide WD. The WD40-domain often comprises several of the WD40-repeats each forming a beta-pleated sheet in a propeller blade 1,2. WD40 proteins are crucially involved in several physiological functions as diverse as signal transduction, RNA processing, remodeling the cytoskeleton, regulation of vesicular traffic, and cell cycle control 3-5. Their immediate purpose most likely is to serve as platforms for the assembly of protein complexes and to mediate protein-protein interactions 6. The WD40 protein family member WDR16 is highly conserved having homologs in invertebrates and vertebrates including flies and humans 7. In rat, expression of WDR16 was mainly observed in testis and in ependymal cells of the brain, and with reduced expression in lungs. Its expression profile, especially during ependymal development, indicated a correlation to the presence of motile cilia whereas in cells harboring primary cilia WDR16 could not be detected 7. By immunofluorescence, WDR16 was found in the cytosol of rat testicular cells, especially in early spermatocytes and pachytene spermatocytes showing a uniform and unspecific localization. Sperm flagella stained negative for WDR16 but in Western blots the tail fraction of bull sperm revealed WDR16 7. Overall, these results indicated that WDR16 is a marker for motile cilia-bearing cells. WDR16 depletion in zebrafish caused hydrocephalus, however, ciliary movement remained intact. Similarly, the ependymal layer did not display visibl...

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“…Many teratozoospermia have been reported to cause male infertility 1 . One of the most extreme forms of teratozoospermia is acephalic spermatozoa syndrome, which is characterized by decapitated flagella, very few intact spermatozoa, and tailless sperm heads in the semen, and it finally leads to severe male infertility 2 , 3 . In the past decades, studies show the acephalic spermatozoa syndrome with familial clustering, suggesting that this is a syndrome with a specific genetic origin 4 – 8 .…”

Section: Introductionmentioning

confidence: 99%

The missing linker between SUN5 and PMFBP1 in sperm head-tail coupling apparatus

Zhang

Liu

et al. 2021

Nat Commun

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The sperm head-to-tail coupling apparatus (HTCA) ensures sperm head-tail integrity while defective HTCA causes acephalic spermatozoa, rendering males infertile. Here, we show that CENTLEIN is indispensable for HTCA integrity and function, and that inactivation of CENTLEIN in mice leads to sperm decapitation and male sterility. We demonstrate that CENTLEIN directly interacts with both SUN5 and PMFBP1, two proteins localized in the HTCA and related with acephalic spermatozoa syndrome. We find that the absence of Centlein sets SUN5 and PMFBP1 apart, the former close to the sperm head and the latter in the decapitated tail. We show that lack of Sun5 results in CENTLEIN and PMFBP1 left in the decapitated tail, while disruption of Pmfbp1 results in SUN5 and CENTLEIN left on the detached sperm head. These results demonstrate that CENTLEIN cooperating with SUN5 and PMFBP1 participates in the HTCA assembly and integration of sperm head to the tail, indicating that impairments of CENTLEIN might be associated with acephalic spermatozoa syndrome in humans.

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Lack of a head in human spermatozoa from sterile patients: a syndrome associated with impaired fertilization

Cited by 86 publications

References 11 publications

Odf2 haploinsufficiency causes a new type of decapitated and decaudated spermatozoa, Odf2-DDS, in mice

Odf2 haploinsufficiency causes a new type of decapitated and decaudated spermatozoa, Odf2-DDS, in mice

The WD40-protein CFAP52/WDR16 is a centrosome/basal body protein and localizes to the manchette and the flagellum in male germ cells

The missing linker between SUN5 and PMFBP1 in sperm head-tail coupling apparatus

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