Mouse model of chorea-acanthocytosis exhibits male infertility caused by impaired sperm motility as a result of ultrastructural morphological abnormalities in the mitochondrial sheath in the sperm midpiece

2018 ◽  
Vol 503 (2) ◽  
pp. 915-920 ◽  
Author(s):  
Omi Nagata ◽  
Masayuki Nakamura ◽  
Hitoshi Sakimoto ◽  
Yuka Urata ◽  
Natsuki Sasaki ◽  
...  
2019 ◽  
Vol 57 (2) ◽  
pp. 89-95 ◽  
Author(s):  
Weiyu Li ◽  
Huan Wu ◽  
Fuping Li ◽  
Shixiong Tian ◽  
Zine-Eddine Kherraf ◽  
...  

BackgroundMale infertility is a prevalent issue worldwide, mostly due to the impaired sperm motility. Multiple morphological abnormalities of the sperm flagella (MMAF) present aberrant spermatozoa with absent, short, coiled, bent and irregular-calibre flagella resulting in severely decreased motility. Previous studies reported several MMAF-associated genes accounting for approximately half of MMAF cases.Methods and resultWe conducted genetic analysis using whole-exome sequencing in 88 Han Chinese MMAF probands. CFAP65 homozygous mutations were identified in four unrelated consanguineous families, and CFAP65 compound heterozygous mutations were found in two unrelated cases with MMAF. All these CFAP65 mutations were null, including four frameshift mutations (c.1775delC [p.Pro592Leufs*8], c.3072_3079dup [p.Arg1027Profs*41], c.1946delC [p.Pro649Argfs*5] and c.1580delT [p.Leu527Argfs*31]) and three stop-gain mutations (c.4855C>T [p.Arg1619*], c.5270T>A [p.Leu1757*] and c.5341G>T [p.Glu1781*]). Additionally, two homozygous CFAP65 variants likely affecting splicing were identified in two MMAF-affected men of Tunisian and Iranian ancestries, respectively. These biallelic variants of CFAP65 were verified by Sanger sequencing and were absent or very rare in large data sets aggregating sequence information from various human populations. CFAP65, encoding the cilia and flagella associated protein 65, is highly and preferentially expressed in the testis. Here we also generated a frameshift mutation in mouse orthologue Cfap65 using CRISPR-Cas9 technology. Remarkably, the phenotypes of Cfap65-mutated male mice were consistent with human MMAF.ConclusionsOur experimental observations performed on both human subjects and on Cfap65-mutated mice demonstrate that the presence of biallelic mutations in CFAP65 causes the MMAF phenotype and impairs sperm motility.


Author(s):  
F Han ◽  
M Z Dong ◽  
W L Lei ◽  
Z L Xu ◽  
F Gao ◽  
...  

Abstract Protein phosphatase 4 (PPP4) is a protein phosphatase that, although highly expressed in the testis, currently has an unclear physiological role in this tissue. Here, we show that deletion of PPP4 catalytic subunit gene Ppp4c in the mouse causes male-specific infertility. Loss of PPP4C, when assessed by light microscopy, did not obviously affect many aspects of the morphology of spermatogenesis, including acrosome formation, nuclear condensation and elongation, mitochondrial sheaths arrangement and “9 + 2” flagellar structure assembly. However, the PPP4C mutant had sperm tail bending defects (head-bent-back), low sperm count, poor sperm motility and had cytoplasmic remnants attached to the middle-piece of the tail. The cytoplasmic remnants were further investigated by transmission electron microscopy to reveal that a defect in cytoplasm removal appeared to play a significant role in the observed spermiogenesis failure and resulting male infertility. A lack of PPP4 during spermatogenesis causes defects that are reminiscent of oligoasthenoteratospermia (OAT), which is a common cause of male infertility in humans. Like the lack of functional PPP4 in the mouse model, OAT is characterized by abnormal sperm morphology, low sperm count and poor sperm motility. Although the causes of OAT are probably heterogeneous, including mutation of various genes and environmentally induced defects, the detailed molecular mechanism(s) has remained unclear. Our discovery that the PPP4C-deficient mouse model shares features with human OAT might offer a useful model for further studies of this currently poorly understood disorder.


PLoS Genetics ◽  
2020 ◽  
Vol 16 (9) ◽  
pp. e1009020
Author(s):  
Ya-Yun Wang ◽  
Chih-Chun Ke ◽  
Yen-Lin Chen ◽  
Yu-Hua Lin ◽  
I-Shing Yu ◽  
...  

2018 ◽  
Vol 93 (4) ◽  
pp. 853-859 ◽  
Author(s):  
F. Gurbuz ◽  
S. Desai ◽  
F. Diao ◽  
D. Turkkahraman ◽  
F. Wranitz ◽  
...  

2021 ◽  
Vol 21 ◽  
Author(s):  
Naina Kumar ◽  
Namit Kant Singh

: Male infertility is rising now-a-days and accounts for major part of infertility cases worldwide. Novel tests are being developed for better detection and management of male infertility. Though there are many tests available for diagnosing male infertility like acrosome reaction rate, hemizona assay, in vivo or in vitro sperm penetration assay, sperm DNA damage tests, but semen analysis is most commonly used initial test for male infertility. It is usually associated with failure to detect cause in many cases, as seminal composition gets affected by a number of factors and can give false reports. Furthermore, it does not give any information about defects in capacitation, sperm Zona Pellucida interaction and sperm’s ability to fertilize oocytes. This results in failure of detection and delayed management of male infertility. Hence, the present review was conducted to identify various sperm proteins that play significant role in spermatogenesis, sperm motility, sperm-Zona Pellucida interaction and fertilization. These proteins can be used in future as markers of male infertility and will aid in better detection and management of male infertility. Methodology: Search for literature was made from 1970 to 2020 from various databases like PUBMED, SCOPUS, Google Scholar on sperm proteins and their role in male fertility using keywords: “sperm protein as bio-markers”, “novel sperm proteins as markers of infertility”, “Sperm proteins essential for capacitation, sperm motility and oocyte fertilization”. Inclusion criteria: All full-length research articles, systematic reviews, meta-analysis or abstracts on sperm proteins and male infertility published in English language in peer-reviewed journals were considered.


2019 ◽  
Vol 38 (5) ◽  
pp. 769-778 ◽  
Author(s):  
Huan Wu ◽  
Weiyu Li ◽  
Xiaojin He ◽  
Chunyu Liu ◽  
Youyan Fang ◽  
...  

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
O Somova ◽  
H Ivanova ◽  
N Sotnyk ◽  
K Kovalenko ◽  
I Feskova

Abstract Study question To evaluate the effect of platelet-rich plasma (PRP) testicular injections on spermogram parameters of men with severe oligoasthenoteratozoospermia (OAT). Summary answer The PRP testicular injections have beneficial effects on spermatogenesis and enhance sperm concentration and motility in infertile men with OAT. What is known already The use of PRP therapy in assisted reproductive technologies is debatable. Despite the recent evidence of its positive effects in promoting endometrial and follicular growth, data from clinical studies are limited. There are only a few papers on the effectiveness of PRP therapy in the treatment of male infertility and sexual dysfunction. In more detail, the influence of PRP on spermatogenesis was carried out only on experimental animals. Although the mechanisms of its action have not yet been clarified, it is assumed that PRP, containing many biologically active molecules, realizes its effect through the tissue regeneration and cell proliferation. Study design, size, duration This prospective study included 68 men (34.6±5.2) years old with severe OAT (≤4 million/ml, motility ≤30%, normal sperm morphology ≤1%) receiving hormonal and antioxidant (AO) therapy during 6 months before in vitro fertilization cycles. 33 of them were injected once with autologous PRP (0.5 ml in each testicle). Spermogram and testosterone level were analyzed before the treatment and in 3, 4 and 6 months after it. Participants/materials, setting, methods: Sperm concentration, motility and morphology in ejaculate of 33 men of PRP group were compared with those in the group of 35 men without PRP within 6 months of starting the treatment. Total and free testosterone level were measured in blood serum. PRP was prepared by centrifuging the patient’s own blood in the anticoagulant-containing tubes. The final concentration of platelets in the obtained sample was 950.000 – 1.250 000 cells in 1 ml. Main results and the role of chance 4 months after the PRP injection, sperm concentration and motility increased in 18 of 33 men of the PRP group compared with the baseline (before the treatment) – 4.2 (1.0; 6.9) vs 1.4 (0.1; 3.4) mln/ml (p < 0.05) and 36.7 (30.6; 45.8) vs 17.7 (6.7; 28.2)% respectively (p < 0.05).The maximum increase in sperm motility (but not in sperm concentration!) was observed in 24 men in 6 months – 49.6 (39.6; 56.4)% (p < 0.05). Percent of morphologically normal spermatozoa in ejaculate slightly increased only in 12 men in that time period from 0–1% to 1–2%. The total testosterone level was 2.4 times higher than the baseline (31.6±7.2 vs 13.2±4.3 nmol/l, p < 0.05), the free testosterone level was 1.8 times higher (14.5±3.5 vs 7.9±3.0 pgl/ml, p < 0.05). Unlike the PRP group, in the group of men without PRP treatment, the sperm parameters did not changed compared with the baseline in 4 months after the starting hormonal and AO treatment. A significant increase of sperin concentration was observed only in 17 of 35 patients in 6 months. Sperm motility and percent of morphologically normal spermatozoa after the treatment did not differ from the baseline. Changes in the testosterone levels were similar to changes in PRP group. Limitations, reasons for caution Only young and middle-aged men were considered in the study. Large randomized controlled studies are required to confirm the PRP therapy efficacy and safety of f various fertility disorders. There are also no standardized protocols for PRP preparation. Wider implications of the findings: PRP therapy may have great potential for the treatment of male infertility and improving spermatogenesis. Optimization of methods of PRP preparation and dosage of testicular injections can enhance reproductive outcomes in assisted reproductive technologies. Trial registration number Not applicable


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

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