Jong Kwan Park

Ca2+ Signaling Tools Acquired from Prostasomes Are Required for Progesterone-Induced Sperm Motility

Prostate-derived vesicles provide sperm with calcium signaling proteins required for progesterone-induced motility. Delivering Sperm a Toolkit Progesterone stimulates complex calcium signals in human sperm that have been implicated in enhancing their motility. Noting that sperm are structurally simple cells with a minimal complement of organelles, Park et al. explored the possibility that prostasomes (small vesicles secreted by the prostate) might deliver a “calcium toolkit” to sperm to enable these complex calcium responses. Analyses of sperm isolated before prostasome exposure revealed that, indeed, fusion with prostasomes led to the acquisition in sperm of various proteins implicated in calcium signaling and enabled the progesterone-dependent mobilization of calcium from internal stores. Moreover, prostasomal proteins promoted progesterone-dependent sperm motility and enhanced the ability of mouse sperm to fertilize ova. Progesterone-induced calcium ion (Ca2+) signals in the neck region of sperm play a pivotal role in promoting sperm motility. Here, we show that a long-lasting Ca2+ signal required for sperm motility in response to progesterone depends on their pH-dependent fusion with prostasomes, which are small vesicles secreted by the prostate. We found that prostasome fusion led to the transfer of progesterone receptors, cyclic adenosine diphosphoribose (cADPR)–synthesizing enzymes, ryanodine receptors (RyRs), and other Ca2+ signaling tools from prostasomes to the sperm neck. Progesterone-induced sperm motility relied on cADPR-mediated Ca2+ mobilization through RyR located on acidic Ca2+ stores, followed by Ca2+ entry through store-operated channels. Treatment of prostasome-fused sperm with a cADPR antagonist or fusion with prostasomes in which type 2 RyR was depleted resulted in low fertilization rates, reduced sperm motility, or both. Thus, we conclude that sperm motility depends on the acquisition of Ca2+ signaling tools from prostasomes.

Effects of male silkworm pupa powder on the erectile dysfunction by chronic ethanol consumption in rats

Erectile dysfunction (ED) is a highly prevalent disorder that affects millions of men worldwide. ED is now considered an early manifestation of atherosclerosis, and consequently, a precursor of systemic vascular disease. This study was designed to investigate the effects of male silkworm pupa powder (SWP) on the levels of nitric oxide synthase (NOS) expression, nitrite, and glutathione (GSH); lipid peroxidation; libido; and erectile response of the corpus cavernosum of the rat penis. We induced ED in the study animals by oral administration of 20% ethanol over 8 weeks. The SWP-treated male rats were divided into 3 groups that were orally administered 200, 400, and 800 mg/kg. The libido of the SWP-administered male rats was higher than that of the ethanol control group. In addition, the erectile response of the corpus cavernosum was restored in males on SWP administration, to a level similar to that of the normal group without ED. The testosterone concentration did not increase significantly. The lipid peroxidation in the corpus cavernosum of the male rats administered SWP decreased significantly. In contrast, compared to the ethanol group, SWP-administered male rats showed increased GSH levels in the corpus cavernosum. The level of nitrite and NOS expression in the corpus cavernosum of SWP-administered male rats increased significantly. These results indicated that SWP effectively restored ethanol-induced ED in male rats.

Seminal CD38 is a pivotal regulator for fetomaternal tolerance

Significance In natural matings, semen delivers spermatozoa and immunoregulatory fluids to the female reproductive tract. Here, a soluble form of CD38 (sCD38) is shown to play an important role in facilitating maternal immune tolerance against the fetus by inducing the development of uterine tolerogenic DCs and forkhead box P3+ (Foxp3+) regulatory T cells. Deficiency of sCD38 in seminal fluid increased the rates of loss of allogeneic fetuses, and this loss was rescued by a direct injection of recombinant sCD38 into the uterus. Thus, seminal sCD38 acts as a pivotal immune suppressor for establishing maternal immune tolerance against the fetus. sCD38 could potentially be used to prevent failed pregnancies. A successful pregnancy depends on a complex process that establishes fetomaternal tolerance. Seminal plasma is known to induce maternal immune tolerance to paternal alloantigens, but the seminal factors that regulate maternal immunity have yet to be characterized. Here, we show that a soluble form of CD38 (sCD38) released from seminal vesicles to the seminal plasma plays a crucial role in inducing tolerogenic dendritic cells and CD4+ forkhead box P3+ (Foxp3+) regulatory T cells (Tregs), thereby enhancing maternal immune tolerance and protecting the semiallogeneic fetus from resorption. The abortion rate in BALB/c females mated with C57BL/6 Cd38−/− males was high compared with that in females mated with Cd38+/+ males, and this was associated with a reduced proportion of Tregs within the CD4+ T-cell pool. Direct intravaginal injection of sCD38 to CBA/J pregnant mice at preimplantation increased Tregs and pregnancy rates in mice under abortive sonic stress from 48 h after mating until euthanasia. Thus, sCD38 released from seminal vesicles to the seminal plasma acts as an immunoregulatory factor to protect semiallogeneic fetuses from maternal immune responses.

Comparisons of apomorphine‐induced erection and spontaneous erection in rats by telemetric assessment of intracavernosal pressure

Although there are several methods for assessing erectile function in rats, the standard methods for telemetric monitoring have not been established. Theoretically assessment of spontaneous erection (SE) seems to be a physiologic method but it needs long measuring time and additional efforts. Apomorphine‐induced erection (AIE) is one available and simple method; however, the correlation with SE has not been assessed. We compared erection profiles of AIE and SE in normal and two disease rat models using telemetric assessment of intracavernosal pressure (ICP). Seven‐week‐old male Sprague–Dawley rats were assigned to normal control, diabetes mellitus (DM) and hypercholesterolemia (HC) group. After 19 weeks a telemetric pressure sensor (C40; Data Sciences) was surgically implanted in the corpus cavernosum. One week later, ICP was recorded in freely moving rats after intraperitoneal apomorphine (100 μg/kg) injection (AIE) or during SE. Sexual events were visually identified and recorded. Only the pressure increases that occurred during sexual behavior were analyzed. We compared the erectile profiles such as duration, maximal ICP and the area under the curve (AUC, area under time × ICP curves). Two‐way anova revealed no significant effect of the measuring methods on the mean AUC (F1,43 = 2.756, p‐value = 0.104), but a significant effect of different disease models on mean AUC (two‐way anova: F2,43 = 12.929, p‐value < 0.001) was observed. The mean AUC of normal control rats was significantly higher than that of DM and HC rats (Bonferroni post hoc test: p < 0.001 and p = 0.001, respectively). ICP measurements using a telemetric device showed no significant difference in AUC between AIE and SE. AIE is easy and requires less time than SE measurements. Therefore, AIE could be a useful method to evaluate ICP in rats.

Pharmacokinetics of a new orally soluble film formulation of sildenafil administered without water.

OBJECTIVEnTo compare the pharmacokinetic profiles and to assess bioequivalence of a newly developed orally soluble film formulation of sildenafil, taken without water, with those of a conventional formulation of sildenafil.nnnMETHODSnThis study was conducted in a population of healthy subjects as an open-label, randomized sequence, two-period, two-formulation, single-dose, crossover design. The subjects were randomly assigned to 1 of 2 sequences of the two formulations: an orally soluble film (OSF) of 50 mg sildenafil as the test drug and a film-coated tablet (FCT) of 50 mg sildenafil as the reference drug. Blood samples were collected at intervals from 0 to 24 hours after administration. Plasma concentrations of sildenafil and its active metabolite N-desmethyl sildenafil were analyzed using a liquid chromatography/tandem mass spectrometry method.nnnRESULTSn48 healthy male subjects completed the study. The geometric mean (CV%) for Cmax in the OSF and FCT formulations were 267.21 (4.68%) ng/mL and 285.97 (5.32%) ng/mL, respectively. The geometric mean for AUClast in the OSF and FCT formulations were 664.48 (4.40%) ng x h/mL and 647.96 (4.63%) ng x h/mL, respectively. The geometric mean for AUCinf in the OSF and FCT formulations were 685.65 (4.37%) ng x h/mL and 666.28 (4.60%) ng x h/ mL, respectively. The 90% confidence intervals of the ratios of the geometric means of the Cmax, AUClast, and AUCinf were 0.844 - 1.030, 0.961 - 1.091, and 0.965 - 1.093, respectively.nnnCONCLUSIONSnThe OSF sildenafil formulation exhibited no significant differences in its pharmacokinetics compared with those of the FCT formulation. Therefore this convenient OSF sildenafil formulation, which can be taken without the need for water or chewing, offers physicians a novel and attractive treatment option for men with erectile dysfunction. *These authors contributed equally to this work.

An open, non-comparative, multicentre study on the impact of alfuzosin on sexual function using the Male Sexual Health Questionnaire in patients with benign prostate hyperplasia

Objectives:u2002 To determine the effect of alfuzosin on sexual function by using the Male Sexual Health Questionnaire (MSHQ) in men with lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH).

Analysis of testicular-internal spermatic vein variation and the recreation of varicocoele in a Sprague-Dawley rat model.

Many laboratories tried to recreate the varicocoele model have met with varied success. To recreate a consistent varicocoele model by exploring the anatomic variability of the testicular‐spermatic venous system in Sprague‐Dawley (SD) rats. Seventy‐two sexually mature SD male rats were randomly divided into three groups containing 24 rats per group. Partial ligation of the left renal vein and internal spermatic vein (ISV) communicating branches to common iliac vein and ISV communicating branches ligation (RVISVCBCIV) or partial ligation of the left renal vein and ISV communicating branches ligation (RVISVCB). The results showed that the mean diameter of the left ISV was significantly increased in the RVISVCBCIV group compared with the control and RVISVCB groups (p < 0.001). Using ISV as the reference, the sensitivity of varicocoele was 71.43%, and the specificity was 80%. In addition, the positive predictive value was 83.33%, and the negative predictive value was 66.67%. Sperm count, motility, Johnsen score and the spermatogenic cell density were lower in the RVISVCBCIV group compared with the control (p < 0.01). The apoptotic index was higher in the RVISVCBCIV group compared with control groups (p < 0.01). The RVISVCBCIV provides a more effective method for establishing a varicocoele‐induced model.