Adverse temporal trends in human semen quality and cryptorchidism in infants have been associated with exposure to environmental chemicals (ECs) during development. Here we report that a population of breeding dogs exhibit a 26 year (1988-2014) decline in sperm quality and a concurrent increased incidence of cryptorchidism in male offspring (1995-2014). A decline in the number of males born relative to the number of females was also observed. ECs, including diethylhexyl phthalate (DEHP) and polychlorinated bisphenol 153 (PCB153), were detected in adult dog testes and commercial dog foods at concentrations reported to perturb reproductive function in other species. Testicular concentrations of DEHP and PCB153 perturbed sperm viability, motility and DNA integrity in vitro but did not affect LH stimulated testosterone secretion from adult testis explants. The direct effects of chemicals on sperm may therefore contribute to the decline in canine semen quality that parallels that reported in the human.
Zika virus (ZIKV) infection of pregnant women can cause congenital malformations including microcephaly, which has focused global attention on this emerging pathogen(1). In addition to transmission by mosquitoes, ZIKV can be detected in the seminal fluid of affected males for extended periods of time and transmitted sexually(2). Here, using a mouse-adapted African ZIKV strain (Dakar 41519), we evaluated the consequences of infection in the male reproductive tract of mice. We observed persistence of ZIKV, but not the closely related Dengue virus (DENV), in the testis and epididymis of male mice, and this was associated with tissue injury that caused diminished testosterone and inhibin B levels, and oligospermia. ZIKV preferentially infected spermatogonia, primary spermatocytes, and Sertoli cells in the testis, resulting in cell death and destruction of the seminiferous tubules. Less damage was observed with a contemporary Asian ZIKV strain (H/PF/2013), in part because this virus replicates less efficiently in mice. The extent to which these observations in mice translate to humans remains unclear, but longitudinal studies of sperm function and viability in ZIKV-infected humans seem warranted.
Sexual dysfunction is one of the diabetic complications in males. The present study aimed to evaluate the antidiabetic effect of α-mangostin and its protective role in sexual dysfunction of streptozotocin (STZ) induced diabetic male rats. Male Wistar rats were divided as control, diabetic control, diabetic rats administered with 25, 50 mg/kg body weight (bw) of α-mangostin and 1 mg/kg bw of gliclazide. The α-mangostin was administered once daily for a period of 55 days. On day 55 animals were sacrificed, serum was analyzed for testosterone levels, and sperm was collected from the epididymis and sperm parameters analyzed. Testis and epididymis were examined for antioxidant enzymes like superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx) levels, lipidperoxidation products, and histopathological alterations. In diabetic rats, sperm count, motile sperms, viable sperms, and hypo-osmotic swelling tail coiled sperms were significantly decreased while sperm malformations increased when compared with normal rats. Serum testosterone levels and testicular 3β and 17 β-hydroxysteroid dehydrogenase levels were significantly decreased in diabetic rats. Significant reduction in testicular and epididymal SOD, catalase, GPx levels, and elevation in lipid peroxidation products were observed. However, α-mangostin treatment showed noteworthy recovery in all parameters towards the control levels. It may therefore be suggested that α-mangostin showed a protective effect against sexual dysfunction in STZ induced diabetic rats.
Testicular infarction is an uncommon finding in paediatric age and is usually due to testicular torsion or trauma causing venous rupture with thrombosis and/or arteriolar obstruction. Other causes of segmental infarction of the testes are represented by polyarteritis nodosa, thromboangioiitis obliterans and hypersensitivity angiitis. A few cases of testicular infarction due to epididymitis have been described in the literature related mainly to adult patients. Epididymitis is usually treated in the outpatient setting with close follow-up, but according to our present experience, and reviewing the literature, there may be some cases in which, surgical exploration is mandatory in order to avoid testicular damage.
Abstract Context: Hibiscus sabdariffa L. (Malvaceae) is a species widely used in folk medicine for the treatment of some disorders. Objective: This study evaluated the effects of H. sabdariffa (HS) on the development of the male reproductive tract in rats following in utero exposure. Materials and methods: Pregnant rats received 250 or 500 mg/kg of HS extract or vehicle from gestational day 12 until day 21 of lactation. Results and discussion: Both doses of HS increased the body weight of male offspring at weaning, without compromising the puberty onset parameters. At puberty, there was a significant increase in the vas deferens absolute weight and a significant reduction in the relative weight of kidney at higher dose. These animals also presented a significant reduction in the sperm number in the caput/corpus of epididymis after exposure to both doses and a reduction in the sperm number in the cauda epididymis for the lower dose. At adulthood, the highest dose significantly reduced the sperm production in relation to controls and both doses provoked a reduction in the relative sperm number in the epididymis without affecting the sperm morphology. Conclusion: These findings demonstrated that maternal exposure to H. sabdariffa can adversely influence the male reproductive system in rats.
Vas deferens ectopia is a rare congenital anomaly frequently associated with anorectal abnormalities and hypospadias. We present a Currarino syndrome case with an ectopic vas deferens terminating in a distal retroiliac ureter. A left vasectomy, ureteral decussation over the iliac vessels and a Cohen’s type ureteral reimplantation were performed. The objectives are to preserve renal function, prevent epididymitis and preserve fertility. There is no evidence in the literature that recommends surgical correction of the vas deferens. Microsurgical epididymal sperm aspiration or testicular sperm extraction combined with intracytoplasmic sperm injection (ICSI) might be a viable strategy for these affected individuals.
Calcineurin inhibitors, cyclosporine A and FK506, are used as immunosuppressant drugs but their adverse effects on male reproductive function remain unclear. The testis expresses somatic calcineurin and a sperm-specific isoform that contains a catalytic subunit (PPP3CC) and a regulatory subunit (PPP3R2). We demonstrate herein that Ppp3cc and Ppp3r2 knockout male mice are infertile with reduced sperm motility due to an inflexible midpiece. Treatment of mice with cyclosporine A or FK506 phenocopies the sperm motility and morphological defects. These defects appear within 4-5 days of treatment indicating that sperm-specific calcineurin confers midpiece flexibility during epididymal transit. Mouse male fertility recovered a week after discontinuing treatment. Since human spermatozoa contain PPP3CC/PPP3R2 as a functional calcineurin, inhibition of sperm-specific calcineurin may lead to the development of a reversible male contraceptive targeting spermatozoa in the epididymis.
ESP1/SPESP1 is a testis specific, post-meiotic gene expressed in round spermatids that encodes equatorial segment protein 1, an intra-acrosomal protein found in the acrosomal matrix and on the luminal surface of the inner and outer acrosomal membranes within the equatorial segment domain of mature spermatozoa. A comparison of testicular protein extracts with caput, corpus and caudal epididymal sperm proteins revealed striking differences in the apparent masses of SPESP1 isoforms. The predominant isoforms of SPESP1 in the testis were 77 and 67 kDa, with 47 kDa forms present to a minor degree. In contrast, SPESP1 isoforms of 47 and 43 kDa were found in caput, corpus and caudal sperm, indicating that SPESP1 undergoes noticeable mass changes during spermiogenesis and/or subsequent transport to the epididymis. On two-dimensional (2D) SDS-PAGE testicular SPESP1 isoforms resolved as a train of pIs from 4.9-5.2. Immunoprecipitated 77 kDa SPESP1 from testis reacted with the glycoprofile stain after 1 and 2-D gel electrophoresis indicating that the 77 kDa testicular isoform was highly glycosylated. One charge variant of the 67 kDa isoform was also glycoprofile positive after 2-D gel resolution. The 47 and 43 kDa isoforms of SPESP1 from epididymal sperm did not stain with glycoprofile suggesting an absence of, or few, glycoprofile sensitive glycoconjugates in epididymal SPESP1. Treatment of testicular extracts with a variety of glycosidases resulted in mass shifts in immunoreactive SPESP1 indicating that testicular SPESP1 was glycosylated and that terminal sialic acid, N- and O- glycans were present. A mixture of deglycosidase enzymes (including PNGase-F, neuraminidase, beta1-4 galactosidase, Eneo-alpha-N-acetylgalactosaminidase, and beta N-acetyl-glucosaminidase) completely eliminated the 77 and 67 kDa SPESP1 bands and resulted in the appearance of 75, 60, 55, 50, 47 and 43 kDa forms, confirming that both the 77 and 67 kDa testicular forms of SPESP1 contain complex carbohydrate residues. Treatment of caudal epididymal sperm with PNGase-F enzymes showed a faint deglycosylated band at 30 kDa, but neuraminidase did not result in any molecular shift, indicating that epididymal sperm SPESP1 did not contain sialic acid/N-acetylglucosamine residues. These findings are consistent with the hypothesis that SPSPESP1 undergoes significant glycosylation in the testis and the majority of these glycoconjugates are removed by the time sperm reach the caput epididymis. Studies of the fate of SPESP1 after the acrosome reaction localized SPESP1 to the equatorial segment region in both non-capacitated and in capacitated, acrosome reacted sperm. During capacitation, SPESP1 underwent proteolysis resulting in a 27 kDa fragment. Zona free oocytes incubated with recSPESP1 protein showed complementary binding sites on the microvillar oolemmal domain. RecSPESP1 and anti-recSPESP1 antibody inhibited in vitro fertilization.
Zika virus (ZIKV) is an emerging pathogen causally associated with serious sequelae in fetuses, inducing fetal microcephaly and other neurodevelopment defects. ZIKV is primarily transmitted by mosquitoes, but can persist in human semen and sperm, and sexual transmission has been documented. Moreover, exposure of type-I interferon knockout mice to ZIKV results in severe damage to the testes, epididymis and sperm. Candidate ZIKV vaccines have shown protective efficacy in preclinical studies carried out in animal models, and several vaccines have entered clinical trials. Here, we report that administration of a synthetic DNA vaccine encoding ZIKV pre-membrane and envelope (prME) completely protects mice against ZIKV-associated damage to the testes and sperm and prevents viral persistence in the testes following challenge with a contemporary strain of ZIKV. These data suggest that DNA vaccination merits further investigation as a potential means to reduce ZIKV persistence in the male reproductive tract.
Transplantation of testicular cells and tissues has been studied for the investigation of immunology of the testis, which is an immunologically privileged organ. However, reports of transplant of the testis at organ level have been extremely limited because of technical difficulties of the orthotopic testis transplantation (OTT) in experimental animals. In the present study, we developed a new and simple model of the heterotopic testis transplantation (HTT), which is donor testis transplantation into the cervical region of recipients, in a syngeneic model in rats [donor Lewis (LEW) graft to LEW recipient]. The duration of HTT was significantly shorter and success rate higher than that of OTT. To histologically evaluate HTT, the local immune responses were compared among the syngeneic model, an acute rejection allogeneic model [donor Augustus Copenhagen Irish (ACI) graft to LEW recipient] and a chronic rejection allogeneic model (donor F344 graft to LEW recipient) at postoperative day 3. We found that allogeneic ACI grafts resulted in mild and not severe orchitic lesions, whereas immune responses of allogeneic F344 grafts seemed intact and were not significantly different from those of syngeneic LEW grafts. These results suggest that our new operative procedure will be useful in future for the investigation of the testicular immunology.