Impaired Sperm Motility Research Articles

Loss-of-function mutations in SPEF2 cause multiple morphological abnormalities of the sperm flagella (MMAF)

BackgroundMultiple morphological abnormalities of the sperm flagella (MMAF) is a kind of severe teratozoospermia. Patients with the MMAF phenotype are infertile and present aberrant spermatozoa with absent, short, coiled, bent...

Effects of bisphenol A exposure on DNA integrity and protamination of mouse spermatozoa.

Bisphenol A is widely used in the manufacture of polycarbonate plastics and has caused increasing concern over its potential adverse impacts on spermatogenesis. However, the effect of bisphenol A on spermiogenesis is yet to be explored. To evaluate whether bisphenol A has adverse effects on DNA integrity and protamination of spermatogenic cell. Newborn male mice were subcutaneously injected with bisphenol A (0.1, 5mg/kg body weight, n=15) or coin oil (control group, n=20) daily from post-natal day 1 until 35. At post-natal day 70, epididymis caudal spermatozoa and testes were collected. Sperm count, sperm motility, and sperm morphology were analyzed. The sperm chromatin structure assay was performed to examine the sperm DNA fragmentation. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) method was used to assess apoptosis of spermatogenic cells. The ultrastructural features of testicular sections were examined under a transmission electron microscope. Western blot and RT-PCR were used to detect the expression levels of transition protein (Tnp) 1 and Tnp2, protamine (Prm) 1 and Prm2 protein, and mRNA in mice testes. Bisphenol A significantly reduced sperm counts, impaired sperm motility, and increased the percentage of malformed spermatozoa. Poor sperm chromatin integrity and increased TUNEL-positive spermatogenic cells were also observed in mice exposed to bisphenol A. Ultrastructural analysis of testes showed that bisphenol A exposure caused incomplete chromatin condensation, retention of residual cytoplasm, and abnormal acrosome formation. In addition, the relative expression levels of Tnp2 and Prm2 in mice testes decreased significantly in bisphenol A groups. Our findings identified that neonatal bisphenol A exposure may negatively contribute to the sperm quality in adult mice. Mechanistically, we showed that bisphenol A reduced sperm chromatin integrity along with increased DNA damage, which may be due to poor protamination of spermatozoa.

Risks to Health and Well-Being From Radio-Frequency Radiation Emitted by Cell Phones and Other Wireless Devices.

Radiation exposure has long been a concern for the public, policy makers, and health researchers. Beginning with radar during World War II, human exposure to radio-frequency radiation1 (RFR) technologies has grown substantially over time. In 2011, the International Agency for Research on Cancer (IARC) reviewed the published literature and categorized RFR as a “possible” (Group 2B) human carcinogen. A broad range of adverse human health effects associated with RFR have been reported since the IARC review. In addition, three large-scale carcinogenicity studies in rodents exposed to levels of RFR that mimic lifetime human exposures have shown significantly increased rates of Schwannomas and malignant gliomas, as well as chromosomal DNA damage. Of particular concern are the effects of RFR exposure on the developing brain in children. Compared with an adult male, a cell phone held against the head of a child exposes deeper brain structures to greater radiation doses per unit volume, and the young, thin skull's bone marrow absorbs a roughly 10-fold higher local dose. Experimental and observational studies also suggest that men who keep cell phones in their trouser pockets have significantly lower sperm counts and significantly impaired sperm motility and morphology, including mitochondrial DNA damage. Based on the accumulated evidence, we recommend that IARC re-evaluate its 2011 classification of the human carcinogenicity of RFR, and that WHO complete a systematic review of multiple other health effects such as sperm damage. In the interim, current knowledge provides justification for governments, public health authorities, and physicians/allied health professionals to warn the population that having a cell phone next to the body is harmful, and to support measures to reduce all exposures to RFR.

Improvement of Sperm Quality in Hyperviscous Semen following DNase I Treatment.

Semen hyperviscosity impairs sperm motility and can lead to male infertility. This prospective study aimed at assessing the ability of exogenous DNase in improving sperm quality, taking into consideration that DNase has been found in the seminal plasma of several species and that neutrophils release chromatin in order to trap bacteria. A total of seventy-seven semen samples with high seminal viscosity (HSV) as the study group and sixty-two semen samples with normal seminal viscosity (NSV) as the control group were compared in this analysis. These semen samples were divided into three groups of receiving treatment (a) with DNase I at 37°C for 15 min, (b) by density gradient centrifugation, and (c) with a combination of the above two methods. Following a fifteen-minute treatment of hyperviscous semen, the motility of spermatozoa in 83% of semen samples increased to a statistically significant degree. On the contrary, DNase treatment of semen with normal viscosity had no such effects. The above treatment was also accompanied by a significant increase in the percentage of normal spermatozoa, resulting in a major decrease of the teratozoospermia index. Comparison between semen samples that underwent density gradient centrifugation following DNase I treatment, to those collected after density gradient treatment alone, showed that in the first case the results were more spectacular. The evaluation of each preparation in terms of yield (% total progressively motile sperm count after treatment in relation to the initial total sperm count) revealed that the combined approach resulted in 29.8% vs. 18.5% with density treatment alone (p=0.0121). DNase I treatment results in an improvement of sperm motility and morphology and could be beneficial to men with hyperviscous semen in assisted reproduction protocols.

Microelements in seminal and serum plasma are associated with fresh semen quality in Yorkshire boars

This study aimed to explore associations between semen quality and trace element level in serum and seminal plasma in Yorkshire boars. Semen quality of 112 Yorkshire boars was assessed for 13 weeks to calculate semen utilization rate, which was then divided into three categories: low utilization rate group (LG, < 60% utilization rate), medium utilization rate group (MG, 60–80%), and high utilization rate group (HG, > 80%). After grouping, serum and seminal plasma samples of selected boars were collected to determine concentrations of 10 elements including Ca, Mg, Cu, Fe, Zn, Mn, Se, Cr, Pb and Cd using inductively coupled plasma mass spectrometry. Results showed the increase of semen utilization rate was accompanied by the increase of sperm motility and the decrease of abnormal sperm rate among three groups (P < 0.01). Serum Fe concentration in LG boars was lower than that in HG boars (P < 0.05). Regression analysis revealed serum Fe concentration was positively correlated with sperm motility (r = 0.251; P < 0.05), while negatively correlated with abnormal sperm rate (r = −0.207; P < 0.05). However, MG and HG boars had lower serum Se concentration than LG boars (P < 0.05), and serum Se concentration contribution to sperm motility varied in a quadratic manner (Sperm motility = −0.0004 Se(serum)2 +0.136 Se+74.06; r = 0.300; P < 0.01). Semen utilization rate tended to decrease with the increase of seminal plasma Pb concentration (P = 0.09). Regression analysis exhibited seminal plasma Pb negatively related to sperm motility (r = −0.237; P < 0.05), while positively correlated with abnormal sperm rate (r = 0.237; P < 0.05). Furthermore, seminal plasma Pb was the most influential factor among trace element in serum and seminal plasma on sperm motility basing on the generalized linear model analysis (P < 0.05). Sperm motility decreased by approximately 3.47% when seminal plasma Pb concentration increased from 0 μg/L to 11.16 μg/L. In conclusion, deficiency of serum Fe reduces semen utilization rate by impairing sperm motility and morphology, whereas excessive serum Se decreases sperm motility. More importantly, the mere existence of seminal plasma Pb has more impact on semen quality than other trace elements in serum and seminal plasma in Yorkshire boars.

Long-term ethanol consumption promotes changes in β-defensin isoform gene expression and induces structural changes and oxidative DNA damage to the epididymis of rats.

Chronic alcohol ingestion causes sexual dysfunction, impairs sperm motility and fertility, and changes semen quality. Considering the key role of epididymis in sperm development, the aim of the present study was to evaluate the effects of long-term ethanol consumption on epididymis changes, including alterations in β-defensin isoform gene expression, oxidative stress, and pathological changes, such as cell proliferation and fibrosis in the epididymis of rats. In this study, male Wistar rats were equally divided into control and ethanol (4.5 g/kg BW) groups. After six weeks of treatment, the results revealed the proliferation of epididymis cells, fibrosis in the epididymis tissue, and a significant rise in the level of 8-OHdG and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase in the ethanol group, compared with the control group. Moreover, the ethanol group showed an increase in the gene expression of epididymal β-defensin isoforms 15 and 21 and a reduction in the gene expression of β-defensin isoforms 27 and 30, compared with the controls. These findings indicate that ethanol-induced epididymal damage and sperm abnormalities might be partly associated with changes in β-defensin isoforms and epididymal structure, mediated by the increased activities of 8-OHdG and NADPH oxidase.

Two isoforms of the RAC-specific guanine nucleotide exchange factor TIAM2 act oppositely on transmission ratio distortion by the mouse t-haplotype.

Transmission ratio distortion (TRD) by the mouse t-haplotype, a variant region on chromosome 17, is a well-studied model of non-Mendelian inheritance. It is characterized by the high transmission ratio (up to 99%) of the t-haplotype from t/+ males to their offspring. TRD is achieved by the exquisite ability of the responder (Tcr) to trigger non-Mendelian inheritance of homologous chromosomes. Several distorters (Tcd1-Tcd4), which act cumulatively, together promote the high transmission ratio of Tcr and the t-haplotype. Molecularly, TRD is brought about by deregulation of Rho signaling pathways via the distorter products, which impair sperm motility, and the t-sperm specific rescue of sperm motility by the responder. The t-sperm thus can reach the egg cells faster than +-sperm and fertilize them. Previously we have shown that the responder function is accomplished by a dominant negative form of sperm motility kinase (SMOKTCR), while the distorter functions are accomplished by the Rho G protein regulators TAGAP, FGD2 and NME3 proposed to function in two oppositely acting pathways. Here we identify the RAC1-specific guanine nucleotide exchange factor TIAM2 as modifier of t-haplotype TRD. Tiam2 is expressed in two isoforms, the full-length (Tiam2l) and a short transcript (Tiam2s). Tiam2s expression from the t-allele is strongly increased compared to the wild-type allele. By transgenic approaches we show that Tiam2s enhances t-haplotype transmission, while Tiam2l has the opposite effect. Our data show that a single modifier locus can encode different gene products exerting opposite effects on a trait. They also suggest that the expression ratio of the isoforms determines if the outcome is an enhancing or a suppressive effect on the trait.

Impact of Spirulina Supplementation on Semen Parameters in Patients with Idiopathic Male Infertility: A Pilot Randomized Trial.

To evaluate the efficacy of therapy with spirulina supplement on semen parameters in patients with idiopathic male infertility. A total of 40 men with idiopathic infertility were randomly assigned into two groups. Group A received 2 g spirulina supplement as well as conventional regimen for the treatment of infertility selected by their physician (220 mg/day zinc sulfate, 500mg/day L-carnitine, and 50 mg/day clomiphene) during 12 weeksof the study, while group B received placebo plus conventional therapy during the study period. Semen parameters were analyzed at baseline and at the end of the study as a primary endpoint. The secondary endpoint was the rate of pregnancy occurring in the patients. wives. No significant differences in semen parameters were observed between the spirulina and control groups [count (16.43 vs. 46.00, P = .164), motility (51.00 vs. 48.7, P = .008), and morphology (47.50 vs. 15.00, P = NA)]. Our results showed a pregnancy rate of 5% in the spirulina group versus 0% in the control group. This pilot randomized trial provides initial evidence on the possible beneficial effects of spirulina mainly in patients with impaired sperm motility or morphology. Due to the limited sample size, further larger randomized trials not only at the level of semen parameters but at the scope of paternity are required to confirmthese potential benefits.

Loss-of-function mutations in QRICH2 cause male infertility with multiple morphological abnormalities of the sperm flagella

Aberrant sperm flagella impair sperm motility and cause male infertility, yet the genes which have been identified in multiple morphological abnormalities of the flagella (MMAF) can only explain the pathogenic mechanisms of MMAF in a small number of cases. Here, we identify and functionally characterize homozygous loss-of-function mutations of QRICH2 in two infertile males with MMAF from two consanguineous families. Remarkably, Qrich2 knock-out (KO) male mice constructed by CRISPR-Cas9 technology present MMAF phenotypes and sterility. To elucidate the mechanisms of Qrich2 functioning in sperm flagellar formation, we perform proteomic analysis on the testes of KO and wild-type mice. Furthermore, in vitro experiments indicate that QRICH2 is involved in sperm flagellar development through stabilizing and enhancing the expression of proteins related to flagellar development. Our findings strongly suggest that the genetic mutations of human QRICH2 can lead to male infertility with MMAF and that QRICH2 is essential for sperm flagellar formation.

Syndromic infertility.

Infertility due to genetic mutations that cause other defects, besides infertility, is defined as syndromic. Here we describe three of these disorders for which we perform genetic tests. 1) Hypopituitarism is an endocrine syndrome characterized by reduced or absent secretion of one or more anterior pituitary hormones with consequent dysfunction of the corresponding peripheral glands. Deficiencies in all the hormones is defined as pan-hypopituitarism, lack of two or more hormones is called partial hypopituitarism, whereas absence of a single hormone is defined as selective hypopituitarism. Pan-hypopituitarism is the rarest condition, whereas the other two are more frequent. Several forms exist: congenital, acquired, organic and functional. 2) The correct functioning of the hypothalamic-pituitary-gonadal axis is fundamental for sexual differentiation and development during fetal life and puberty and for normal gonad function. Alteration of the hypothalamic-pituitary system can determine a condition called hypogonadotropic hypogonadism, characterized by normal/low serum levels of the hormones FSH and LH. 3) Primary ciliary dyskinesia is frequently associated with infertility in males because it impairs sperm motility (asthenozoospermia). Primary ciliary dyskinesia is a group of genetically and phenotypically heterogeneous disorders that show morpho-structural alterations of the cilia. Adult women with primary ciliary dyskinesia can be subfertile and have an increased probability of extra-uterine pregnancies. This is due to delayed transport of the oocyte through the uterine tubes. (www.actabiomedica.it)

Spermatologic characteristics and sperm motility alterations caused by short-term copper exposure in Brook Trout Salvelinus fontinalis

Spermatozoa movement in many aquatic animals with external fertilization is directly related to the external aqueous environment. In particular, environmental toxic metals can cause harmful effects and impair sperm cell functions. The high concentrations of copper (Cu) may be harmful for aquatic animals, while low levels are required for metabolic interactions. Herein, we investigated the effect of different copper concentration [0 mg L−1 (Control), .5 mg L−1, 1 mg L–1, and 2 mg L−1] on spermatozoa of brook trout Salvelinus fontinalis. Motility and survival of sperm cells were assessed. Our results indicated that Cu exposure caused to an evident decrease in motility and longevity of spermatozoa with increasing concentrations (p < .05). Overall, we showed that Cu exposure can impair sperm motility of S. fontinalis. Our study suggested that sperm motility has the potential to be a sensitive bioindicator of freshwater environmental pollution.

Novel homozygous CFAP69 mutations in humans and mice cause severe asthenoteratospermia with multiple morphological abnormalities of the sperm flagella

BackgroundMale infertility is a major issue of human reproduction health. Asthenoteratospermia can impair sperm motility and cause male infertility. Asthenoteratospermia with multiple morphological abnormalities of the flagella (MMAF) presents abnormal...

Methylmercury-induced testis damage is associated with activation of oxidative stress and germ cell autophagy

Methylmercury (MeHg) is a widespread environmental pollutant and causes a serious hazard to testicular development and spermatogenesis. However, molecular mechanisms underlying male reproductive toxicity induced by MeHg remain elusive. The objective of this study was to explore the effects of MeHg on autophagy induction in germ cells (GCs). In this study, we showed that orally administered MeHg 10 mg/kg per day for five consecutive days resulted in reduced sperm count and impaired sperm motility. Noteworthy, MeHg impaired the seminiferous tubule of rats and increased the apoptotic index of GCs of rats. Furthermore, the levels of the autophagy markers light chain 3-II (LC3-II) and beclin-1 were significantly increased following MeHg treatment, possibly via inhibiting the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (m-TOR) signaling pathway. In addition, these effects are concomitant with the overgeneration of reactive oxygen species (ROS) and the decreased expression of the antioxidant enzymes superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT). Interestingly, supplementation with MeHg induced oxidative DNA damage in testes of rats. Taken together, our data indicated that MeHg stimulates GC apoptosis through oxidative stress and autophagy, which may be the mechanism responsible for the regulation of testis function and differentiation following MeHg exposure.

Serum and Seminal Plasma Element Concentrations in Relation to Semen Quality in Duroc Boars.

Element concentrations in serum and seminal plasma were studied in Duroc boars with different semen quality characteristics. Based on the utilization rate of 2174 ejaculates from June to August in 2016, a total of 166 Duroc boars were allocated into three groups: low utilization rate group (LG, 0 to 60% utilization rate), medium utilization rate group (MG, 60 to 80%), and high utilization rate group (HG, 80 to 100%). Serum and seminal plasma samples were collected, and element levels were analyzed using inductively coupled plasma mass spectrometry. The results showed that LG boars had higher concentrations of serum copper and seminal plasma cadmium compared with MG and HG boars (P < 0.05), and serum copper and seminal plasma cadmium were negatively correlated with sperm motility, while positively correlated with the abnormal sperm rate. We observed the abnormal sperm rate increased by approximately 4.53% with serum copper increasing from 1.63 to 2.44mg/L, while sperm motility decreased by approximately 2.85% with seminal plasma cadmium increasing from 0 to 0.82μg/L. Moreover, serum iron and manganese levels in the LG group were significantly reduced compared with the HG boars (P < 0.05), and the two elements were negatively correlated with the abnormal sperm rate (P < 0.05). In conclusion, excessive copper and absence of iron and manganese in serum as well as higher seminal plasma cadmium may reduce the utilization rate of semen by impairing sperm motility and morphology, indicating the importance of adding and monitoring microelements in boar diet.

Sleep restriction during peripuberty unbalances sexual hormones and testicular cytokines in rats.

Spermatogenesis and steroidogenesis are not fully established during puberty. Especially during this period, children and adolescents may be chronically sleep deprived due to early school hours and constant exposure to artificial light and interactive activities. We have previously shown that sleep restriction (SR) during peripuberty impairs sperm motility and has consequences on epididymal development in rats. Thus, this study aimed to evaluate the effect of SR during peripuberty on sexual hormones and its impact on testicular tissue. Rats were subjected to 18 h of SR per day for 21 days or were maintained as controls (C) in the same room. The circulating luteinizing hormone levels were decreased in SR rats without changes in the follicle stimulating hormone levels. Plasma and intratesticular testosterone and corticosterone in the SR group were increased in relation to C group. These alterations impair testicular tissue, with decreased IL-1β, IL-6, and TNFα levels in the testis and diminished seminiferous epithelium height and Sertoli cell number. SR also increased testicular lipid peroxidation with no alteration in antioxidant profiles. There were no significant changes in sperm parameters, seminiferous tubule diameter, histopathology, spermatogenesis kinetics, neutrophil and macrophage recruitment, and IL-10 concentration. Our results show that SR unbalances sexual hormones and testicular cytokines at a critical period of sexual maturation. These changes lead to lipid peroxidation in the testes and negatively influence the testicular tissue, as evidenced by diminished seminiferous epithelium height-with apoptosis of germinative cell-and Sertoli cell number.

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

Chorea-acanthocytosis (ChAc) is an autosomal recessive hereditary disease characterized by neurodegeneration in the striatum and acanthocytosis caused by loss-of-function mutations in the Vacuolar Protein Sorting 13 Homolog A (VPS13A) gene, which encodes chorein. We previously produced a ChAc-model mouse with a homozygous deletion of exons 60–61 in Vps13a, which corresponded to the human disease mutation. We found that male ChAc-model mice exhibited complete infertility as a result of severely diminished sperm motility. Immunocytochemical study revealed that chorein-like immunoreactivity is abundant only in the midpiece, mitochondria-rich region, of the sperm of wild type mice. They showed no significant differences from wild types in terms of the adenosine 5′-triphosphate (ATP) concentration of their sperm, sperm count, or sexual activity. Electron microscopy revealed abnormal ultrastructural morphology of the mitochondria in the midpiece of sperm from ChAc-model mice. These results suggest that chorein is essential in mouse sperm for the maintenance of ultrastructural mitochondrial morphology and sperm motility.

Sperm DNA Integrity is Unaffected by Thiopurine Treatment in Men With Inflammatory Bowel Disease.

Sperm DNA integrity, concentration, and motility are suspected to be altered by thiopurines (azathioprine [AZA] and 6-mercaptopurine [6-MP]). We investigated the impact of thiopurines on semen quality in men with inflammatory bowel disease [IBD], by a comprehensive panel of semen analyses. Semen from 40 men with IBD, in remission on AZA/6-MP therapy, was prospectively collected and compared with samples from 40 healthy volunteers. Paired samples [off and on AZA/6-MP] were obtained from a subset of IBD patients, and blood and semen were collected to determine 6-MP transmission to the ejaculate. Sperm DNA fragmentation was evaluated via sperm chromatin structure assay [SCSA] and Comet analysis. Conventional World Health Organization [WHO] parameters, i.e. semen volume and sperm concentration, motility, and morphology, were assessed. Additionally, we measured thioguanine nucleotide [TGN] incorporation in sperm cell DNA. Sperm DNA fragmentation levels did not differ between men with IBD on AZA/6-MP and healthy volunteers when evaluated by SCSA [p = 0.23] and Comet analysis [p = 0.72]. IBD patients on AZA/6-MP had significantly lower total and progressive sperm motility than healthy volunteers [48.5% versus 64.5%, p = 0.0003; 27.4% versus 43.3%, p = 0.0004; respectively], with no differences in concentration, volume, or morphology. The same trend was observed in the 10 paired samples. TGN incorporation was not detectable in sperm DNA, but 6-MP was detected in seminal plasma and correlated to blood levels [rs = 0.79, p = 0.02]. Thiopurines do not increase sperm DNA fragmentation but may impair sperm motility in this IBD cohort. Our findings support existing epidemiological data that thiopurine therapy is safe during preconception and should not be abandoned.

Parabens generate reactive oxygen species in human spermatozoa.

Parabens are used as antimicrobial preservative agent in many commercial products including cosmetics and pharmaceuticals. Weak oestrogenic and antiandrogenic activities have been attributed to parabens in invitro and invivo studies. In this study, human spermatozoa were exposed to different concentrations of an equimolar paraben mixture containing methyl, ethyl, propyl and butylparaben as well as to methylparaben alone at a concentration that is typical of commercially available vaginal lubricants. The induction of oxidative stress and DNA damage was then assessed at different time points. Our results demonstrate that the paraben mixture was capable of stimulating the generation of mitochondrial and cytosolic reactive oxygen species (ROS), inhibiting sperm motility and viability in a dose-dependent manner. The ability of individual parabens to activate ROS generation and induce oxidative DNA damage was related to alkyl chain length. At the concentration used clinically, methylparaben inhibited sperm motility after both 2 and 5h exposure (p<0.05) and affected cell viability (p<0.01) while augmenting ROS production and oxidative DNA damage. However, DNA fragmentation was not evident following methylparaben exposure. Based on these results, we conclude that, at the concentrations used in commercially available formulations, parabens may impair sperm motility, enhance the generation of mitochondrial ROS and stimulate the formation of oxidative DNA adducts. Taken together, these data underline the potential cytotoxic and genotoxic impact of such compounds in a clinical setting.

RNASET2 impairs the sperm motility via PKA/PI3K/calcium signal pathways.

Asthenozoospermia is one of the leading causes of male infertility owing to a decline in sperm motility. Herein, we determined if there is a correlation between RNASET2 content on human spermatozoa and sperm motility in 205 semen samples from both asthenozoospermia patients and normozoospermia individuals. RNASET2 content was higher in sperm from asthenozoospermia patients than in normozoospermia individuals. On the other hand, its content was inversely correlated with sperm motility as well as progressive motility. Moreover, the inhibitory effect of RNASET2 on sperm motility was induced by incubating normozoospermic sperm with RNase T2 protein. Such treatment caused significant declines in intracellular spermatozoa PKA activity, PI3K activity and calcium level, which resulted in severely impaired sperm motility, and the sperm motility was largely rescued by cAMP supplementation. Finally, protein immunoprecipitation and mass spectrometry identified proteins whose interactions with RNASET2 were associated with declines in human spermatozoa motility. AKAP4, a protein regulating PKA activity, coimmunoprecipated with RNASET2 and they colocalized with one another in the sperm tail, which might contribute to reduced sperm motility. Thus, RNASET2 may be a novel biomarker of asthenozoospermia. Increases in RNASET2 can interact with AKAP4 in human sperm tail and subsequently reduce sperm motility by suppressing PKA/PI3K/calcium signaling pathways.

An miR-200 Cluster on Chromosome 23 Regulates Sperm Motility in Zebrafish

Besides its well-documented roles in cell proliferation, apoptosis, and carcinogenesis, the function of the p53-microRNA axis has been recently revealed in the reproductive system. Recent studies indicated that miR-200 family members are dysregulated in nonobstructive azoospermia patients, whereas their functions remain poorly documented. The aim of this study was to investigate the function of the miR-200 family on zebrafish testis development and sperm activity. There was no substantial difference in testis morphology and histology between wild-type (WT) and knockout zebrafish with deletion of miR-200 cluster on chromosome 6 (chr6-miR-200-KO) or on chromosome 23 (chr23-miR-200-KO). Interestingly, compared with WT zebrafish, the chr6-miR-200-KO zebrafish had no difference on sperm motility, whereas chr23-miR-200-KO zebrafish showed significantly improved sperm motility. Consistently, ectopic expression of miR-429a, miR-200a, and miR-200b, which are located in the miR-200 cluster on chromosome 23, significantly reduced motility traits of sperm. Several sperm motility-related genes, such as amh, wt1a, and srd5a2b have been confirmed as direct targets of miR-200s on chr23. 17α-ethynylestradiol (EE2) exposure resulted in upregulated expression of p53 and miR-429a in testis and impairment of sperm motility. Strikingly, in p53 mutant zebrafish testis, the expression levels of miR-200s on chr23 were significantly reduced and accompanied by a stimulation of sperm motility. Moreover, the upregulation of miR-429a associated with EE2 treatment was abolished in testis with p53 mutation. And the impairment of sperm activity by EE2 treatment was also eliminated when p53 was mutated. Together, our results reveal that miR-200 cluster on chromosome 23 controls sperm motility in a p53-dependent manner.