Prostate-derived IL-1β upregulates expression of NMDA receptor in the paraventricular nucleus and shortens ejaculation latency in rats with experimental autoimmune prostatitis / 亚洲男科学杂志(英文版)

Experimental autoimmune prostatitis (EAP)-induced persistent inflammatory immune response can significantly upregulate the expression of N-methyl-D-aspartic acid (NMDA) receptors in the paraventricular nucleus (PVN). However, the mechanism has not yet been elucidated. Herein, we screened out the target prostate-derived inflammation cytokines (PDICs) by comparing the inflammatory cytokine levels in peripheral blood and cerebrospinal fluid (CSF) between EAP rats and their controls. After identifying the target PDIC, qualified males in initial copulatory behavior testing (CBT) were subjected to implanting tubes onto bilateral PVN. Next, they were randomly divided into four subgroups (EAP-1, EAP-2, Control-1, and Control-2). After 1-week recovery, EAP-1 rats were microinjected with the target PDIC inhibitor, Control-1 rats were microinjected with the target PDIC, while the EAP-2 and Control-2 subgroups were only treated with the same amount of artificial CSF (aCSF). Results showed that only interleukin-1β(IL-1β) had significantly increased mRNA-expression in the prostate of EAP rats compared to the controls (P < 0.001) and significantly higher protein concentrations in both the serum (P = 0.001) and CSF (P < 0.001) of the EAP groups compared to the Control groups. Therefore, IL-1β was identified as the target PDIC which crosses the blood-brain barrier, thereby influencing the central nervous system. Moreover, the EAP-1 subgroup displayed a gradually prolonged ejaculation latency (EL) in the last three CBTs (all P < 0.01) and a significantly lower expression of NMDA NR1 subunit in the PVN (P = 0.043) compared to the respective control groups after a 10-day central administration of IL-1β inhibitors. However, the Control-1 subgroup showed a gradually shortened EL (P < 0.01) and a significantly higher NR1 expression (P = 0.004) after homochronous IL-1β administration. Therefore, we identified IL-1β as the primary PDIC which shortens EL in EAP rats. However, further studies should be conducted to elucidate the specific molecular mechanisms through which IL-1β upregulates NMDA expression.

Mu-opioid receptors in the paraventricular nucleus regulate ejaculatory behaviors via the sympathetic nerve system in male rats / 中华男科学杂志

Objective@#To explore the effects of the mu-opioid receptor (MOR) in the paraventricular nucleus (PVN) on the ejaculatory behaviors of male rats and its potential mechanisms.@*METHODS@#Male SD rats with normal ejaculation ability were mated with female ones in hormone-induced estrus. After bilateral PVN microinjection of D-Ala-2-Me-Phe-4-Gly-ol enkephalin (DAGO) or D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2 (CTAP) with an inserted catheter, the male animals were observed for mount latency (ML), mount frequency (MF), intromission latency (IL), intromission frequency (IF), ejaculation latency (EL), ejaculation frequency (EF), post-ejaculation interval (PEI), and intromission ratio (IR). The lumbar sympathetic nerve activity (LSNA) of the rats was recorded using the PowerLab data acquisition hardware device, and the levels of norepinephrine (NE) in the peripheral plasma were measured by ELISA following microinjection of saline or different doses of DAGO or CTAP.@*RESULTS@#Neither CTAP nor DGAO significantly affected the ML of the male rats (P > 0.05). DGAO remarkably increased IF (P < 0.01) and MF (P < 0.01), prolonged IL (P < 0.01), EL (P < 0.01) and PEI (P < 0.01), and reduced EF (P <0.01) and IR (P < 0.05). On the contrary, CTAP markedly decreased IF (P < 0.01) and MF (P < 0.01), shortened IL (P < 0.01), EL (P < 0.01) and PFI (P < 0.01), and elevated EF (P < 0.01) and IR (P < 0.01). Additionally, DAGO decreased LSNA in a dose-dependent manner and reduced the NE level in the peripheral plasma. CTAP, however, not only offset the effects of DAGO on LSNA, but also significantly increased LSNA.@*CONCLUSIONS@#MOR in PVN inhibits ejaculatory behaviors in male rats by weakening LSNA, which has provided some theoretical evidence for the use of highly selective opioids in the treatment of premature ejaculation.

Clinical application of the disposable vasographic interventional therapy kit in vasoseminal vesiculography / 中华男科学杂志

Objective@#To investigate the success rate and safety of percutaneous vasoseminal vesiculography with the disposable vasographic interventional therapy kit (VITK).@*METHODS@#This study included ninety-six 19－65 (mean 43) years old male patients with infertility, hematospermia, seminal vesicle cyst, ejaculatory duct cyst, ejaculatory dysfunction, or vas deferens injury, with disease courses varying from 1 month to 7 years. With an open, multi-centered, single-group, self-controlled design and using the disposable VITK, we treated the patients by percutaneous vasoseminal vesiculography via injection of contrast medium into the vas deferens cavity under local anesthesia.@*RESULTS@#Percutaneous vasoseminal vesiculography was successfully performed in 92 (97.87%) of the patients, which revealed abnormal seminal ducts in 51 cases (54.3%). Among the 28 infertile patients, 3 were found with bilateral and 5 with unilateral vas deferens obstruction. Vesiculitis was detected in 36 (81.8%) of the 44 hematospermia patients and bilateral vas deferens abnormality in 5 (38.5%) of the 13 patients with ejaculatory dysfunction. Transectional damage was observed in 2 patients with vas deferens injury induced by bilateral inguinal hernia repair. Three cases of seminal vesicle cyst and 4 cases of ejaculatory cyst were definitely diagnosed by vasoseminal vesiculography.@*CONCLUSIONS@#The disposable vasographic interventional therapy kit, with the advantages of simple operation and high safety, deserves a wide clinical application in vasoseminal vesiculography.

Differences in sympathetic nervous system activity and NMDA receptor levels within the hypothalamic paraventricular nucleus in rats with differential ejaculatory behavior / 亚洲男科学杂志(英文版)

Differences in intravaginal ejaculation latency reflect normal biological variation, but the causes are poorly understood. Here, we investigated whether variation in ejaculation latency in an experimental rat model is related to altered sympathetic nervous system (SNS) activity and expression of N-methyl-D-aspartic acid (NMDA) receptors in the paraventricular nucleus of the hypothalamus (PVN). Male rats were classified as "sluggish," "normal," and "rapid" ejaculators on the basis of ejaculation frequency during copulatory behavioral testing. The lumbar splanchnic nerve activity baselines in these groups were not significantly different at 1460 ± 480 mV, 1660 ± 600 mV, and 1680 ± 490 mV, respectively (P = 0.71). However, SNS sensitivity was remarkably different between the groups (P < 0.01), being 28.9% ± 8.1% in "sluggish," 48.4% ± 7.5% in "normal," and 88.7% ± 7.4% in "rapid" groups. Compared with "normal" ejaculators, the percentage of neurons expressing NMDA receptors in the PVN of "rapid" ejaculators was significantly higher, whereas it was significantly lower in "sluggish" ejaculators (P = 0.01). In addition, there was a positive correlation between the expression of NMDA receptors in the PVN and SNS sensitivity (r = 0.876, P = 0.02). This study shows that intravaginal ejaculatory latency is associated with SNS activity and is mediated by NMDA receptors in the PVN.

Establishment of an animal model of primary premature ejaculation / 中华男科学杂志

<p><b>Objective</b>To investigate the feasibility and practicability of establishing an animal model of primary premature ejaculation using the ejaculation distribution theory.</p><p><b>METHODS</b>We induced behavioral estrus in 32 ovariectomized female SD rats by subcutaneous injection of 20 μg estradiol benzoate at 48 hours and 500 μg progesterone at 4 hours before mating them with 49 male rats once a week for six times. During the last three opulations, we observed the male animals for mounting latency (ML), intromission latency (IL), ejaculation latency (EL), postejaculation interval (PEI), mounting frequency (MF), intromission frequency (IF), intromission rate (IR), and ejaculation frequency (EF).</p><p><b>RESULTS</b>Finally, 22 of the male rats were included in this study. The mean EF>33 was deemed rapid ejaculation,EF<1 sluggish ejaculation, and EF 1.5－2.5 normal ejaculation. The EL was significantly shorter in the rapid ejaculation group than in the sluggish and normal ejaculation groups. The IF was the lowest in those with rapid ejaculation. No statistically significant differences were observed in the ML among the three groups of rats.</p><p><b>CONCLUSIONS</b>Based on the mean ejaculation frequency, the male rats with rapid ejaculation were easily screened, and this animal model may play an important role in exploring the mechanisms of primary premature ejaculation.</p>

Pathogenesis of premature ejaculation: a neurobiological approach / 中华男科学杂志

Premature ejaculation (PE) is a most common male sexual dysfunction with complex pathogenesis. An increasing number of scholars agree that PE is a disorder associated with abnormal neurobiology, which involves the central neurotransmitter system, peripheral nerve function of the nerve tissue structure, and neurological biochemistry. This review focuses on the neurobiological mechanisms of PE, expecting to gain a deeper insight into the possible etiology, objective and reliable diagnostic methods, and individualized treatment of the disease.