The Involvement Of Seminal Vesicles And Seminal Plasma Proteins In Premature Ejaculation And Underlying Mechanisms

Premature ejaculation(PE)is probably the most prevalent sexual complaint in men.Myriad biological factors have been proposed to explain PE including hypersensitivity of the glans penis,disturbances in central serotonergic neurotransmission,erectile difficulties and other sexual comorbidities,prostatitis,chronic pelvic pain syndrome,and thyroid disorders.To date,selective serotonin re-uptake inhibitors and topical local anesthetics have become the most frequently used agents in the treatment of PE.However,these drugs are not effective in some patients.It may be useful to explore the etiology of PE to find new targets for a better treatment.Previous studies showed that seminal vesicles(SVs)involved in the process of ejaculation and secreted the majority of seminal plasma proteins.We observed that some patients with PE had large SVs.SVs assessed at rectal ultrasonography can indirectly reflect the different physiological and pathological state of seminal vesicle.This study aimed to explore the relationship between the changes of SVs structure and PE by comparing SVs on ultrasound between patients with PE and control subjects,and to select proteins related to SVs by comparing the difference of seminal plasma proteins between patients with PE and healthy subjects.This could be the foundation for further study to explore the underlying mechanism of premature ejaculation.Part I The relationship between SVs on ultrasound and PEAim:To evaluate the relationship between the structure of SV on ultrasound and PE.Methods:The cross-sectional study included 44 outpatients with PE and 44 male volunteers without PE,and the size of SV was compared.Self-estimated intravaginal ejaculatory latency time(IELT),the Premature Ejaculation Diagnostic Tool(PEDT),the International Index of Erectile Function-15(IIEF)and the National Institutes of Health Chronic Prostatitis Symptom Index(NIH-CPSI)were used for assessment of symptoms.Results:Compared to the control group,the PE group had significantly higher mean anterior-posterior diameter(APD)of SV(10.6±2.7 mm vs 8.8±1.9 mm,P<0.001).The optimal mean APD of SV cutoff level was 9.25 mm for PE with modest sensitivity(61.4%)and specificity(77.3%).In the PE group,PEDT was also higher with a mean APD of SV?9.25 mm compared with mean APD of SV<9.25 mm(13.5±3.0 mm vs 11.4±2.4 mm,P=0.016).PEDT was significantly correlated with the mean APD of SV(r=0.326,P=0.031),even after adjusting for age,IIEF-15 erectile function score and NIH-CPSI pain domain and voiding domain score(Beta=0.347,P=0.036).Conclusions:These results showed that men with a larger mean APD of SV had a higher PEDT score,indicating that the larger SVs might be a potential cause for PE.Transrectal ultrasound of SV could be a useful method in the evaluation of patients with PE.The treatment for seminal vesiculitis might be a potential therapy in patients with PE and ultrasound change in SV.Part II Different expression of proteins in seminal plasma between PE and control groupAim:To compare the relative expression levels of seminal plasma proteins between PE and control subjects.Methods:Tandem mass tag(TMT)method followed by mass spectrometry analysis was used to compare the relative expression levels of seminal plasma proteins between six PE patients and six matched control subjects.Self-estimated intravaginal ejaculatory latency time(IELT),the Premature Ejaculation Diagnostic Tool(PEDT),the International Index of Erectile Function-15(IIEF)and the National Institutes of Health Chronic Prostatitis Symptom Index(NIH-CPSI)were used for assessment of symptoms.Results:A total of 487 kinds of proteins were identified in seminal plasma of six PE patients and six matched control subjects,and 102 proteins were at least 1.5-fold up-or down-regulated.The results of bioinformatics analysis showed that GGT1 and LAMC1 were related to the structural changes of SVs,and APP was associated with neural dysfunction.Conclusions:The expression of seminal plasma proteins in patients with PE and large APD of SVs was different from those of controls.Some differently expressed proteins were related to the structure of SVs and neural function.Further study about GGT1,LAMC1 and APP might open new perspectives in the pathophysiology of PE.Part III Relation between amyloid precursor protein in seminal plasma and penile sympathetic skin response abnormality in lifelong premature ejaculationAim:To determine whether amyloid precursor protein(APP)and A?42 were associated with PE.Methods:Penile sympathetic skin response(PSSR)was measured in 24 lifelong PE patients.APP and A?42 were determined in patients with PE and 10 control subjects.Results:PE patients presented 1.5-fold higher APP(P=0.004)in seminal plasma compared to that of control subjects.APP/C was even 2.0-fold higher(P<0.001)in seminal plasma.A?42 was not different between PE and control group,but A?42/C was significantly higher in PE group(P<0.001).No differences in APP and APP/C were found between PE patients with abnormal PSSR(PEa)and normal PSSR(PEn)group.PEa group presented significantly higher A?42(P=0.007).In addition,A?42/C was also significantly higher in PEa group(P<0.001).A?42/APP was significantly higher in PEa group(P=0.047).The latency of PSSR was negatively correlated with AP42/C(r=-0.436,P=0.033).However,the latency of PSSR was not correlated with APP/C.Conclusions:The results of this study suggested patients with PE and abnormal PSSR had higher APP and A?42 in the seminal plasma.The abnormal PS SR was related to higher A?42.It may be a potential target for the treatment of PE by reducing A?.