Role In Sperm Motility Research Articles

The moderation effect of GSTM1/GSTT1 gene polymorphisms on the association of sperm mitochondrial DNA copy number and sperm mobility

Oxidative stress (OS) is believed to be a significant factor in the decline of semen quality, with mitochondrial DNA copy number (mtDNAcn) serving as a sensitive biomarker for both semen quality and mitochondrial dysfunction resulting from oxidative stress. While glutathione S-transferases (GSTs) are commonly known as ‘antioxidant’ enzymes, there is ongoing debate regarding the relationship between GST genotypes and semen quality. In a study involving 568 male volunteers from the outpatient department of Puyang Reproductive Medicine Center, sperm mtDNAcn, semen quality, and GSTM1/GSTT1 genotypes were analyzed to investigate the potential link between GSTM1/GSTT1 gene variations and semen quality, as well as the impact of GSTs gene variations on the connection between sperm mtDNAcn and semen quality. Adjusting for variables such as age, BMI, smoking, and alcohol consumption, it was found that mtDNAcn was significantly correlated with decreased sperm concentration and total sperm count (b = − 0.109, − 0.128, respectively; P = 0.002, 0.001, respectively). GSTM1 was associated with progressive motility (OR 0.390, 95% CI 0.218, 0.697), Straight line velocity (VSL) (OR = 0.606, 95% CI 0.385, 0.953), and Straightness (STR) (OR 0.604, 95% CI 0.367, 0.994), while GSTT1 was linked to progressive motility (OR 0.554, 95% CI 0.324, 0.944) and Beat crossover frequency (OR 0.624, 95% CI 0.397, 0.982). The GSTT1 was found to moderate the relationship between mtDNAcn and sperm motility parameters linearity (LIN), STR, and Wobble (WOB), with additive interaction effects observed between GSTT1 and mtDNAcn on LIN, STR, and WOB (P for interaction = 0.008, 0.034, 0.010, respectively). Overall, this study suggests that GSTT1 and GSTM1 gene variations may play a role in sperm motility, with GSTT1 potentially influencing the impact of oxidative stress on sperm motility.

Proteomics and Metabolic Characteristics of Boar Seminal Plasma Extracellular Vesicles Reveal Biomarker Candidates Related to Sperm Motility.

Although seminal plasma extracellular vesicles (SPEVs) play important roles in sperm function, little is known about their metabolite compositions and roles in sperm motility. Here, we performed metabolomics and proteomics analysis of boar SPEVs with high or low sperm motility to investigate specific biomarkers affecting sperm motility. In total, 140 proteins and 32 metabolites were obtained through differentially expressed analysis and weighted gene coexpression network analysis (WGCNA). Seven differentially expressed proteins (DEPs) (ADIRF, EPS8L1, PRCP, CD81, PTPRD, CSK, LOC100736569) and six differentially expressed metabolites (DEMs) (adenosine, beclomethasone, 1,2-benzenedicarboxylic acid, urea, 1-methyl-l-histidine, and palmitic acid) were also identified in WGCNA significant modules. Joint pathway analysis revealed that three DEPs (GART, ADCY7, and NTPCR) and two DEMs (urea and adenosine) were involved in purine metabolism. Our results suggested that there was significant correlation between proteins and metabolites, such as IL4I1 and urea (r = 0.86). Furthermore, we detected the expression level of GART, ADCY7, and CDC42 in sperm of two groups, which further verified the experimental results. This study revealed that several proteins and metabolites in SPEVs play important roles in sperm motility. Our results offered new insights into the complex mechanism of sperm motility and identified potential biomarkers for male reproductive diseases.

Lipidomic and transcriptomic characteristics of boar seminal plasma extracellular vesicles associated with sperm motility

Seminal plasma extracellular vesicles (SPEVs) play an important role in regulating sperm motility by delivering various cargoes, such as miRNAs, mRNAs, proteins and metabolites. However, information on the lipid compositions of SPEVs and their roles in semen quality is limited. Here, we performed high-throughput transcriptomic and lipidomic analysis on SPEVs isolated from 20 boars with high or low sperm motility. Then, we evaluated the lipid composition and gene expression characteristics of SPEVs and identified the specific lipids and genes related to sperm motility. As a result, a total of 26 lipid classes were identified in SPEVs, and five subclasses, CerG2, CerG3, LPE, LPS and TG, were significantly different in boars with high and low sperm motility. In addition, 195 important lipids and 334 important genes were identified by weighted gene coexpression analysis (WGCNA) and differential expression analysis. We observed that several important genes and lipids in SPEVs potentially influence sperm motility via glycerophospholipid metabolism, glycerolipid metabolism, the sphingolipid signaling pathway and the ferroptosis pathway. Furthermore, we found a significant correlation between the content of 22 lipids and the expression levels of 67 genes (|cor| > 0.8, P < 0.05). Moreover, we observed that three important gene-lipid linkages (CerG1 (d22:0/24:0) - RCAN3, Cer (d18:1/24:0) - SCFD2 and CerG1 (d18:0/24:1) - SCFD2) were strongly correlated with sperm motility. Based on the results, some genes and lipids in SPEVs may play important roles in sperm motility by interacting with sperm through important pathways.

NGF, EPO, and IGF-1 in the Male Reproductive System.

Several studies have demonstrated interesting results considering the implication of three growth factors (GFs), namely nerve growth factor (NGF), erythropoietin (EPO), and the insulin-like growth factor-I (IGF-1) in the physiology of male reproductive functions. This review provides insights into the effects of NGF, EPO, and IGF-1 on the male reproductive system, emphasizing mainly their effects on sperm motility and vitality. In the male reproductive system, the expression pattern of the NGF system varies according to the species and testicular development, playing a crucial role in morphogenesis and spermatogenesis. In humans, it seems that NGF positively affects sperm motility parameters and NGF supplementation in cryopreservation media improves post-thaw sperm motility. In animals, EPO is found in various male reproductive tissues, and in humans, the protein is present in seminal plasma and testicular germ cells. EPO receptors have been discovered in the plasma membrane of human spermatozoa, suggesting potential roles in sperm motility and vitality. In humans, IGF-1 is expressed mainly in Sertoli cells and is present in seminal plasma, contributing to cell development and the maturation of spermatozoa. IGF-1 seems to modulate sperm motility, and treatment with IGF-1 has a positive effect on sperm motility and vitality. Furthermore, lower levels of NGF or IGF-1 in seminal plasma are associated with infertility. Understanding the mechanisms of actions of these GFs in the male reproductive system may improve the outcome of sperm processing techniques.

The adenosine A2A receptor in human sperm: its role in sperm motility and association with in vitro fertilization outcomes.

The involvement of ATP and cAMP in sperm function has been extensively documented, but the understanding of the role of adenosine and adenosine receptors remains incomplete. This study aimed to examine the presence of adenosine A2A receptor (A2AR) and study the functional role of A2AR in human sperm. The presence and localization of A2AR in human sperm were examined by western blotting and immunofluorescence assays. The functional role of A2AR in sperm was assessed by incubating human sperm with an A2AR agonist (regadenoson) and an A2AR antagonist (SCH58261). The sperm level of A2AR was examined by western blotting in normozoospermic and asthenozoospermic men to evaluate the association of A2AR with sperm motility and in vitro fertilization (IVF) outcomes. A2AR with a molecular weight of 43 kDa was detected in the tail of human sperm. SCH58261 decreased the motility, penetration ability, intracellular Ca2+ concentration, and CatSper current of human sperm. Although regadenoson did not affect these sperm parameters, it alleviated the adverse effects of SCH58261 on these parameters. In addition, the mean level of A2AR in sperm from asthenozoospermic men was lower than that in sperm from normozoospermic men. The sperm level of A2AR was positively correlated with progressive motility. Furthermore, the fertilization rate during IVF was lower in men with decreased sperm level of A2AR than in men with normal sperm level of A2AR. These results indicate that A2AR is important for human sperm motility and is associated with IVF outcome.

Cpne1 deficiency preserves sperm motility under Ca2+ channel blockade.

Calcium ions (Ca2+) play crucial roles in sperm motility and fertilization. The copine (CPNE) family comprises several Ca2+-dependent phospholipid-binding proteins. Of these, CPNE1 is extensively expressed in mammalian tissues; however, its precise role in testicular development and spermatogenesis is yet to be fully characterized. In this study, we used proteomics to analyze testicular biopsies and found that levels of CPNE1 were significantly reduced in patients with non-obstructive azoospermia (defective spermatogenesis) compared to those in patients with obstructive azoospermia (physiological spermatogenesis). In mice, CPNE1 is expressed at various stages of germ cell development and is associated with the Golgi apparatus. Ultimately, CPNE1 is expressed in the flagella of mature sperms. To further examine the role of CPNE1, we developed a Cpne1 knockout mouse model. Analysis showed that the loss of Cpne1 did not impair testicular development, spermatogenesis, or sperm morphology and motility in physiological conditions. When treated with gadolinium (III) chloride or 2-aminoethoxydiphenyl borate, known inhibitors of store-operated Ca2+ entry, Ca2+ signals and sperm motility were significantly compromised in wild-type mice; however, both mechanisms were conserved in KO mice. These results suggested that CPNE1 is dispensable for testicular development, spermatogenesis or sperm motility in physiological conditions. In addition, CPNE1 may represent a target of Ca2+ channel inhibitors and may therefore be implicated in the regulation of Ca2+ signaling and sperm motility.

Isolation and Characterization of Submitochondrial Reticulum Complex Associated with Midpiece of Bovine Cauda Epididymal Sperm

The mitochondrial sheath of mammalian spermatozoa adheres to an underlying organized network of electron-dense material termed the submitochondrial reticulum (SMR). The objective of the present study is to characterize the structural components of the SMR. We have isolated SMR fractions from midpieces of bovine cauda sperm. SDS-PAGE of SMR fractions revealed four major polypeptides of 56kDa, 54kDa, 34kDa, and 31kDa. Proteomic analyses of the four polypeptides revealed that 56kDa and 54kDa polypeptides identified as glycerol kinase and 34kDa and 31kDa polypeptide identified as VDAC2 and VDAC3, respectively (Voltage-Dependent Anion-Selective Channel Protein 2/3). Western blots of midpiece stained with anti-56kDa, anti-54KDa, anti-34kDaVDAC2, and anti-31kDaVDAC3 antibodies demonstrated the presence of 56kDa, 54kDa, 34kDa, and 31kDa immunoreactive bands, respectively. Four polypeptides are localized to midpiece. Glycerol kinase activity was quantitively assayed in tails. We proposed that glycerol kinase and VDAC2/VDAC 3 polypeptides play an important role in sperm motility and in midpiece function.

The Role of Soluble Adenylyl Cyclase in the Regulation of Flagellar Motility in Ascidian Sperm.

Flagellar motility in sperm is activated and regulated by factors related to the eggs at fertilization. In the ascidian Ciona intestinalis, a sulfated steroid called the SAAF (sperm activating and attracting factor) induces both sperm motility activation and chemotaxis. Cyclic AMP (cAMP) is one of the most important intracellular factors in the sperm signaling pathway. Adenylyl cyclase (AC) is the key enzyme that synthesizes cAMP at the onset of the signaling pathway in all cellular functions. We previously reported that both transmembrane AC (tmAC) and soluble AC (sAC) play important roles in sperm motility in Ciona. The tmAC plays a major role in the SAAF-induced activation of sperm motility. On the other hand, sAC is involved in the regulation of flagellar beat frequency and the Ca2+-dependent chemotactic movement of sperm. In this study, we focused on the role of sAC in the regulation of flagellar motility in Ciona sperm chemotaxis. The immunochemical analysis revealed that several isoforms of sAC protein were expressed in Ciona sperm, as reported in mammals and sea urchins. We demonstrated that sAC inhibition caused strong and transient asymmetrization during the chemotactic turn, and then sperm failed to turn toward the SAAF. In addition, real-time Ca2+ imaging in sperm flagella revealed that sAC inhibition induced an excessive and prolonged Ca2+ influx to flagella. These results indicate that sAC plays a key role in sperm chemotaxis by regulating the clearance of [Ca2+]i and by modulating Ca2+-dependent flagellar waveform conversion.

Leptin Receptor Gln223Arg Polymorphism of Human Spermatozoa Associated with Male Infertility in a Chinese Population.

Leptin (LEP) is believed to play a crucial role in male reproduction, while the molecular mechanisms through which LEP affects the male reproductive system are unclear. LEP acts by binding to a leptin receptor (LEPR) which mediates its physiological action, but there are only limited studies on the function of LEPR in human sperm. This study aimed to determine the Gln223Arg polymorphisms of the LEPR gene in human spermatozoa and evaluate their possible relationship with semen variables. The study was performed on Chinese men: 115 healthy subjects and 108 patients with primary and 98 with secondary infertility. Semen samples were obtained from all patients, and semen variables were analyzed. The genotypic and allelic frequencies of Gln223Arg polymorphism in spermatozoa were determined by PCR and restriction fragment length polymorphism (RFLP) analyses. Statistical analyses were performed using the chi-square test, the Kruskal-Wallis test, and the Mann-Whitney test. There were no significant differences in genotypic or allelic frequency distributions of Gln223Arg polymorphism among men with primary infertility, secondary infertility, and controls. Similarly, semen volume and sperm concentration did not differ with the different genotypes in all groups of men. The percentages of motile sperm for AA + AG genotypes in men with primary infertility (31.98%) were significantly lower than those in secondary infertility, and control men with GG genotypes were 34.41% and 59.36%, respectively. At the same time, the percentages of normal morphology sperm for AA + AG genotypes in men with primary infertility (2.93%) were significantly lower than those in secondary infertility and control men with GG genotypes 3.71% and 6.54%, respectively. This study reveals a possible association between the Gln223Arg polymorphism of the LEPR gene in spermatozoa affecting spermatozoal membrane integrity and having a direct role in sperm motility.

The cilia and flagella associated protein CFAP52 orchestrated with CFAP45 is required for sperm motility in mice

Asthenozoospermia characterized by decreased sperm motility is a major cause of male infertility, but the majority of the etiology remains unknown. Here, we showed that the cilia and flagella associated protein 52 (Cfap52) gene was predominantly expressed in testis and its deletion in a Cfap52 knockout mouse model resulted in decreased sperm motility and male infertility. Cfap52 knockout also led to the disorganization of the midpiece-principal piece junction of the sperm tail but had no effect on the axoneme ultrastructure in spermatozoa. Furthermore, we found that CFAP52 interacted with the cilia and flagella associated protein 45 (CFAP45) and knockout of Cfap52 decreased the expression level of CFAP45 in sperm flagellum, which further disrupted the microtubule sliding produced by dynein ATPase. Together, our studies demonstrate that CFAP52 plays an essential role in sperm motility by interacting with CFAP45 in sperm flagellum, providing insights into the potential pathogenesis of the infertility of the human CFAP52 mutations.

The proAKAP4 concentrations in Nelore bull sperm and their relation to FTAI conception rate results

The AKAP4 protein has an essential role in sperm motility, and its precursor, the proAKAP4, is considered a biomarker for sperm quality and fertility. Despite this, proAKAP4 concentration was never evaluated in Bos indicus sperm. Therefore, this study aims to determine the proAKAP4 concentration in the sperm of Nellore bulls and its association with sperm kinetics, morpho-functionality, morphology, and conception rates after fixed-time artificial insemination (FTAI). The bulls (n = 9) used in our study presented sperm characteristics above expected standards for quality. Sperm from each bull was evaluated regarding kinetics by the CASA system, and assessed for mitochondrial functionality, sperm membrane integrity, and morphology. For the FTAI protocol, multiparous Nelore cows (n = 1507) were inseminated with frozen-thawed sperm from the same batches used in the laboratory analysis. Additionally, the sperm proAKAP4 concentration was determined using an ELISA kit. The data were analyzed by linear regression and the significance level was set to 5%. The mean conception rate was 52.52%. The mean proAKAP4 concentration was 25.75 ng/106 spermatozoa. The proAKAP4 concentration positively affected the sperm total and progressive motilities, and conception rates after FTAI (respectively, r2 = 0.49, P = 0.03; r2 = 0.63, P = 0.01; and r2 = 0.51, P = 0.03). Based on the relationship detected in this study, we conclude that the sperm proAKAP4 concentration is a suitable biomarker to predict the quality and fertility of frozen-thawed Bos indicus semen.

Cancer-testis antigen lactate dehydrogenase C4 as a novel biomarker of male infertility and cancer.

A unique lactate dehydrogenase (LDH) isoenzyme designated as lactate dehydrogenase C4 (LDH-C4) is found in mammalian mature testis and spermatozoa. Thus far, LDH-C4 has been well studied with regard to its gene and amino acid sequences, structure, biological properties, and peptide synthesis. Accumulating evidence has shown that LDH-C4 is closely related to spermatic energy metabolism and plays a critical role in sperm motility, capacitation, and fertilization. Defects in the catalytic activity of LDH-C4 are key to pathophysiological abnormalities underlying infertility. LDH-C4 was originally thought to be present only in mature testis and spermatozoa; however, recent studies have implicated LDH-C4 as a cancer-testis antigen (CTA), owing to its aberrant transcription in a broad spectrum of human neoplasms. This review highlights the recent findings on LDH-C4 with particular emphasis on its role in male infertility and tumors.

Pharmacological perturbation of peroxisome-proliferator-activated receptor gamma alters motility and mitochondrial function of bovine sperm.

Sperm transit through the female reproductive relies upon maintenance of sperm motility. Peroxisome-proliferator-activated receptor gamma (PPARγ) is a ligand-activated nuclear transcription factor with roles in glucose metabolism and reproductive processes including placental function. PPARγ roles in the mammalian postejaculatory sperm function are incompletely defined. Determine expression, localization, and functions of PPARγ in postejaculatory bovine sperm. Frozen-thawed bovine sperm from three to four different bulls were pooled and subjected to immunofluorescence and western blot for detection and localization of PPARγ. Functions in sperm energetics were explored through the addition of pharmacological inhibition (GW; GW9662) and activation (Ros; Rosiglitazone) in the culture medium at 0 and 24h under non-capacitating conditions. Samples were analyzed for sperm kinematics (CASA) and mitochondrial membrane potential (MMP; JC-1 fluorophore). PPARγ was detected in bovine sperm and co-localized to the acrosome with re-localization to the equatorial region in acrosome-compromised sperm. The addition of Ros 50µM for 24 h maintained superior total and progressive motility of sperm compared to vehicle control (VC-DMSO 0.01%). The PPARγ antagonist GW 1µM was detrimental to both total and progressive motility. A challenge experiment (Ros + GW) partially rescued total and progressive motility phenotypes observed with GW incubation. GW-treated samples had a lower number of sperm with high MMP at 24 h compared to Ros or VC. The negative GW MMP phenotype was reversed with the addition of Ros + GW. Likewise, GW-treated samples had more sperm with low MMP compared to VC and Ros, and this phenotype was partially restored with Ros + GW. PPARγ is expressed in post-ejaculatory bovine sperm with regulatory roles in sperm motility and MMP. These findings implicate PPARγ as a novel regulator of postejaculatory mammalian sperm energetics through non-canonical signaling mechanisms.

Prevention of Testicular Damage by Indole Derivative MMINA via Upregulated StAR and CatSper Channels with Coincident Suppression of Oxidative Stress and Inflammation: In Silico and In Vivo Validation.

Cis-diamminedichloroplatinum (II) (CDDP) is a widely used antineoplastic agent with numerous associated side effects. We investigated the mechanisms of action of the indole derivative N’-(4-dimethylaminobenzylidene)-2-1-(4-(methylsulfinyl) benzylidene)-5-fluoro-2-methyl-1H-inden-3-yl) acetohydrazide (MMINA) to protect against CDDP-induced testicular damage. Five groups of rats (n = 7) were treated with saline, DMSO, CDDP, CDDP + MMINA, or MMINA. Reproductive hormones, antioxidant enzyme activity, histopathology, daily sperm production, and oxidative stress markers were examined. Western blot analysis was performed to access the expression of steroidogenic acute regulatory protein (StAR) and inflammatory biomarker expression in testis, while expression of calcium-dependent cation channel of sperm (CatSper) in epididymis was examined. The structural and dynamic molecular docking behavior of MMINA was analyzed using bioinformatics tools. The construction of molecular interactions was performed through KEGG, DAVID, and STRING databases. MMINA treatment reversed CDDP-induced nitric oxide (NO) and malondialdehyde (MDA) augmentation, while boosting the activity of glutathione peroxidase (GPx) and superoxide dismutase (SOD) in the epididymis and testicular tissues. CDDP treatment significantly lowered sperm count, sperm motility, and epididymis sperm count. Furthermore, CDDP reduced epithelial height and tubular diameter and increased luminal diameter with impaired spermatogenesis. MMINA rescued testicular damage caused by CDDP. MMINA rescued CDDP-induced reproductive dysfunctions by upregulating the expression of the CatSper protein, which plays an essential role in sperm motility, MMINA increased testosterone secretion and StAR protein expression. MMINA downregulated the expression of NF-κB, STAT-3, COX-2, and TNF-α. Hydrogen bonding and hydrophobic interactions were predicted between MMINA and 3β-HSD, CatSper, NF-κβ, and TNFα. Molecular interactome outcomes depicted the formation of one hydrogen bond and one hydrophobic interaction between 3β-HSD that contributed to its strong binding with MMINA. CatSper also made one hydrophobic interaction and one hydrogen bond with MMINA but with a lower binding affinity of -7.7 relative to 3β-HSD, whereas MMINA made one hydrogen bond with NF-κβ residue Lys37 and TNF-α reside His91 and two hydrogen bonds with Lys244 and Thr456 of STAT3. Our experimental and in silico results revealed that MMINA boosted the antioxidant defense mechanism, restored the levels of fertility hormones, and suppressed histomorphological alterations.

DNAH5 gene and its correlation with linc02220 expression and sperm characteristics.

Numerous pieces of evidence show that many environmental and genetic factors can cause male infertility. Much research in recent years has investigated the function of long non-coding RNAs (lncRNAs) in fertility. The main objective of the current study was to investigate the expression of Dynein Axonemal Heavy Chain 5 (DNAH5) as a gene that plays an essential role in sperm motility in individuals with asthenozoospermia and terato-asthenozoospermia. Alterations in linc02220 expression (located close to the DNAH5 gene), its action potential in DNAH5 regulating, and the correlation between their expression and normal sperm morphology and motility were also examined. This study examined the semen of 31 asthenozoospermia individuals (AZ), 33 terato-asthenozoospermia (TAZ) individuals, and 33 normospermia (NZ) individuals with normal sperm as a control group. The expression levels of DNAH5 and linc02220 in the sperm samples were analyzed by real-time PCR. Gene expression analysis revealed a significant association between DNAH5 expression and sperm motility and morphology (p < 0.0001). The DNAH5 expression levels in the TAZ and AZ groups were also significantly reduced; however, linc02220 was significantly upregulated in both TAZ and AZ groups compared to the NZ group (p < 0.0001). DNAH5 expression in the TAZ and AZ groups was negatively correlated with linc02220 expression, thus, DNAH5 downregulation was associated with linc02220 overexpression (p < 0.05). The gene linc02220 could be a potential regulatory target for DNAH5, and both could affect sperm's normal motility and morphology.

Testosterone level in seminal vesicle fluid is a better indicator of erectile function than serum testosterone in patients with prostate cancer.

Semen comprises prostatic fluid and seminal vesicle fluid, and seminal vesicle fluid contains various factors such as prostaglandin E2 (PGE2), zinc, and testosterone, which play important roles in sperm motility. It is not known whether these factors affect erectile function. In this study, we investigated factors in seminal vesicle fluid that may affect erectile function. After receiving institutional review board approval, we collected seminal vesicle fluid samples from 134 Japanese patients with localized prostate cancer who underwent robot-assisted radical prostatectomy. We examined the relationship between the results of the Sexual Health Inventory for Men (SHIM), erection hardness score, an original questionnaire on the presence or absence of sexual desire, and concentrations of several factors in seminal vesicle fluid (testosterone, PGE2, transforming growth factor β1, and 8-hydroxy-2-deoxyguanosine), as well as the serum testosterone level. Median participant age was 67 (range 51-77) years. Median concentrations were as follows: seminal vesicle testosterone 1.85 (range 0.17-4.32) ng/ml and serum testosterone 4.60 (range 1.75-10.82) ng/ml. When the SHIM score was divided into two groups, seminal vesicle testosterone concentration was significantly increased (p = 0.002) in participants with a SHIM score ≥17, and no significant difference was observed in serum testosterone levels (p = 0.661). Multivariate analysis revealed that seminal vesicle testosterone was significantly correlated with the SHIM score (≥17 vs. <17; odds ratio 2.137, 95% confidence interval 1.148-3.978, p = 0.016). Testosterone levels in seminal vesicle fluid can reflect erectile function in patients with prostate cancer, suggesting that seminal vesicle testosterone is very important for male erectile function.

Testosterone level in seminal vesicle fluid is a better indicator of sexual function than serum testosterone in patients with prostate cancer

ABSTRACT Objective Semen comprises prostatic fluid and seminal vesicle fluid, which makes up the largest proportion. Seminal vesicle fluid contains various factors such as prostaglandin E2 (PGE2), zinc, and testosterone, which play important roles in sperm motility. Although serum testosterone is important in sexual function, many points are unclear regarding correlations between serum testosterone level and erectile function. We hypothesized that testosterone in seminal vesicle fluid may affect sexual function. Methods After receiving institutional review board approval, we collected seminal vesicle fluid samples from 132 Japanese patients with localized prostate cancer who underwent robot-assisted prostatectomy at Kyushu University Hospital from May 2017 to August 2020. We examined the relationship between results of the Sexual Health Inventory for Men (SHIM), Erection Hardness Score (EHS), an original questionnaire (presence or absence of sexual desire), and concentrations of testosterone in seminal vesicle fluid as well as serum testosterone level. Results Median participant age was 68 (range 51–77) years. Median concentrations were as follows: seminal vesicle testosterone 1.85 (range 0.17–4.32) ng/mL, serum testosterone 4.59 (range 1.75–10.82) ng/mL. When SHIM score was divided into two groups, seminal vesicle testosterone concentration was significantly increased (P=0.001) in participants with SHIM score ≥17; no significant difference was observed in serum testosterone (P=0.716). EHS score was also correlated with seminal vesicle testosterone (P=0.031) but not serum testosterone (P=0.380). Multivariate analysis revealed that seminal vesicle testosterone was significantly correlated with SHIM score (≥17 vs. &amp;lt;17, odds ratio: 2.374, 95% confidence interval: 1.244–4.529, P=0.008). Seminal vesicle testosterone was not correlated with age (R2=0.032) or serum testosterone (R2=0.014). Conclusions Testosterone levels in seminal vesicle fluid can reflect sexual function in patients with prostate cancer, suggesting that seminal vesicle testosterone may affect male sexual function. Disclosure Work supported by industry: no.

Ras-related proteins (Rab) play significant roles in sperm motility and capacitation status

Rab proteins are widely known for their involvement in establishing Golgi apparatus and controlling Golgi trafficking in eukaryotic cells. Specifically, Rab proteins play significant roles in acrosome formation and exocytosis. Furthermore, mechanisms involved in the regulation of Rab proteins during capacitation have been identified. However, there has been no direct evaluation to assess the correlation between Rab proteins and sperm function. Consequently, this study was designed to analyze the correlation between Rab proteins and sperm functions. Individually, we analyzed the sperm motility patterns, motion kinematics, capacitation status, and Rab protein expression levels of sperm samples from 31 boars before and after capacitation. As a result, we discovered that Rab3A, Rab5, Rab11, Rab14, and Rab27A correlated with various sperm motility patterns, motion kinematics before capacitation. Rab3A, Rab5, Rab11, Rab14, and Rab34 correlated with various sperm motility patterns, motion kinematics after capacitation. Moreover, Rab4 and Rab34 were associated with capacitation status before capacitation, and Rab3A, 25, and 27A correlated with capacitation status after capacitation. This is the first study to analyze the correlation between Rab proteins and sperm functions. Collectively, our results indicate that specific sperm motility and kinematics, as well as the structural condition of the sperm head and capacitation status, regulate individual Rab protein. Therefore, we expect that the current findings will be used to identify the etiology of idiopathic male infertility patients and to diagnose male fertility and that Rab proteins will be employed as biomarkers to predict and analyze male fertility.

Methamphetamine Downregulates the Sperm-Specific Calcium Channels Involved in Sperm Motility in Rats.

Calcium channels play essential roles in sperm motility. A family of sperm-specific cation channels including CatSper1–4 has been identified as voltage-dependent ion channels that act as sperm motility regulators. Methamphetamine is known to cause apoptosis in seminiferous tubules and affect sperm quality. This research was conducted to investigate the effects of methamphetamine on expression of the CatSper family and Mvh genes. Thirty-six adult Wistar rats were divided into four groups of nine rats each: the control and experimental groups 1, 2, and 3. The control group received no solvents or drugs, but experimental groups 1, 2, and 3 were daily given 0.2 mL of a solution by gavage that contained 0.5, 1, and 2 mg of methamphetamine, respectively, for 45 days. The rats were then anesthetized, and one testis removed from each rat was used in a reverse transcription-polymerase chain reaction (RT-PCR). Analysis of variance (ANOVA) and Tukey’s posthoc test were used to analyze the data at the P < 0.05 significance level. Treatment with methamphetamine resulted in decreased testis and epididymis weights compared to the control rats. The results showed that the mRNA fold expression level of the CatSper family and Mvh genes decreased significantly in experimental groups compared to that in the control (P < 0.05). Methamphetamine decreased the expression levels of the CatSper and Mvh genes, and thus, it seemed that it can increase the probability of infertility through sperm motility reduction by lowering the expression levels of these genes.

Frequency of the STRC-CATSPER2 deletion in STRC-associated hearing loss patients

The STRC gene, located on chromosome 15q15.3, is one of the genetic causes of autosomal recessive mild-to-moderate sensorineural hearing loss. One of the unique characteristics of STRC-associated hearing loss is the high prevalence of long deletions or copy number variations observed on chromosome 15q15.3. Further, the deletion of chromosome 15q15.3 from STRC to CATSPER2 is also known to be a genetic cause of deafness infertility syndrome (DIS), which is associated with not only hearing loss but also male infertility, as CATSPER2 plays crucial roles in sperm motility. Thus, information regarding the deletion range for each patient is important to the provision of appropriate genetic counselling for hearing loss and male infertility. In the present study, we performed next-generation sequencing (NGS) analysis for 9956 Japanese hearing loss patients and analyzed copy number variations in the STRC gene based on NGS read depth data. In addition, we performed Multiplex Ligation-dependent Probe Amplification analysis to determine the deletion range including the PPIP5K1, CKMT1B, STRC and CATSPER2 genomic region to estimate the prevalence of the STRC-CATSPER deletion, which is causative for DIS among the STRC-associated hearing loss patients. As a result, we identified 276 cases with STRC-associated hearing loss. The prevalence of STRC-associated hearing loss in Japanese hearing loss patients was 2.77% (276/9956). In addition, 77.1% of cases with STRC homozygous deletions carried a two copy loss of the entire CKMT1B-STRC-CATSPER2 gene region. This information will be useful for the provision of more appropriate genetic counselling regarding hearing loss and male infertility for the patients with a STRC deletion.