Three hour abstinence as a treatment for high sperm DNA fragmentation: a prospective cohort study.

PURPOSE: This study sought to compare sperm DNA fragmentation (SDF) in semen specimens after 3 days and then after 3 h of abstinence in men presenting for initial infertility evaluation. METHODS: A prospective cohort study of 112 men undergoing their first semen analysis as part of an infertility work-up was conducted. All participants presented with 3 days of abstinence for a semen analysis and DNA-fragmentation test. Both tests were repeated on a second sample collected 3 h after the first ejaculation. DNA-fragmentation was evaluated with the halo test by one of two technicians blinded to duration of abstinence. Variables analyzed include ejaculate volume, sperm concentration and motility, smoking status, cannabis use, initial specimen DNA fragmentation, and use of sperm-directed anti-oxidant formulations. RESULTS: Among all subjects, DNA fragmentation improved in the 3-h abstinence specimen (34.6 ± 19.4% vs. 23.7 ± 16.0%, p = 0.0001). Among subjects with high DNA fragmentation (> 35%) on the initial specimen, 55% improved into the normal range. Semen volume and sperm concentration decreased (3.1 ± 3.3 ml vs. 1.9 ± 0.8 ml, p < 0.01 and 41 ± 39 vs. 32 ± 31 (millions/ml), p = 0.01), while progressive motility tended to increase. Fifty-eight subjects demonstrated ≥ 30% improvement in SDF in the second specimen as compared to the first. Factors found to correlate with > 30% improvement in DNA fragmentation in the 3-h abstinence specimen compared to 3 days were younger age and use of anti-oxidants. CONCLUSION: High SDF can often be managed with a second ejaculation 3 h after the first in infertile couples, including in males with abnormal semen analyses per the 2010 WHO guide. Apart from SDF levels, changes in sperm quality were not clinically significant in the second specimen and did not increase rates of ICSI. However, a second ejaculation after 3 h probably may reduce the necessity of costly and/or invasive ART strategies.

Changes in sexual performance and biochemical characterisation of functional neural regions: A study in serotonin transporter knockout male rats.

To explore the correlation between SERT expression and sexual activities and seek the possible mechanism of SERT in regulating ejaculations, we analysed the sexual activities and biochemical characteristics of five measured neural regions in three rat genotypes (SERT-/- , SERT+/- and SERT+/+ ). The results showed the SERT-/- group showed fewer ejaculations and a longer ejaculation latency than the SERT+/+ group, while the SERT+/- group did not differ significantly from the SERT+/+ group in sexual performance. In addition, the SERT-/- group showed an almost complete absence of SERT mRNA and protein expression in all measured regions. In the SERT+/- group, the SERT mRNA and SERT protein expressions were downregulated by approximately 50% and 35%, respectively, compared to the SERT+/+ group. The SERT-/- group had the highest 5-HT levels, and the 5-HT level in the SERT+/- group was between the other two groups. Besides, the 5-HT levels differed in almost all measured regions of the three groups. Therefore, our study confirmed that SERT played a key role in sexual performance. A certain amount of SERT protein may be critical to normal sexual performance. Hence, Polymorphisms of the SERT gene should still be highlighted for ejaculation regulation research.

Differences in sperm protein abundance and carbonylation level in bull ejaculates of low and high quality.

In breeding and insemination centres, significant variation in bull ejaculate quality is often observed between individuals and also within the same individual. Low-quality semen does not qualify for cryopreservation and is rejected, generating economic loss. The mechanisms underlying the formation of low-quality ejaculates are poorly understood; therefore, the aim of the present study was to investigate the proteomic differences and oxidative modifications (measured as changes in protein carbonylation level) of bull ejaculates of low and high quality. Flow cytometry and computer-assisted sperm analysis were used to assess differences in viability, reactive oxygen species (ROS) level, and sperm motility. To analyse changes in protein abundance, two-dimensional difference gel electrophoresis (2D-DIGE) was performed. Western blotting in conjunction with two-dimensional electrophoresis (2D-oxyblot) was used to quantitate carbonylated sperm proteins. Proteins were identified using matrix-assisted laser desorption/ionisation time-of-flight/time-of-flight spectrometry. High quality ejaculates were characterised by higher sperm motility, viability, concentration, and a lower number of ROS-positive cells (ROS+). We found significant differences in the protein profile between high- and low-quality ejaculates, and identified 14 protein spots corresponding to 10 proteins with differences in abundance. The identified sperm proteins were mainly associated with energetic metabolism, capacitation, fertilisation, motility, and cellular detoxification. High-quality ejaculates were characterised by a high abundance of extracellular sperm surface proteins, likely due to more efficient secretion from accessory sex glands and/or epididymis, and a low abundance of intracellular proteins. Our results show that sperm proteins in low-quality ejaculates are characterised by a high carbonylation level. Moreover, we identified, for the first time, 14 protein spots corresponding to 12 proteins with differences in carbonylation level between low- and high-quality ejaculates. The carbonylated proteins were localised mainly in mitochondria or their immediate surroundings. Oxidative damage to proteins in low-quality semen may be associated with phosphorylation/dephosphorylation disturbances, mitochondrial dysfunction, and motility apparatus disorders. Our results contribute to research regarding the mechanism by which low- and high-quality ejaculates are formed and to the identification of sperm proteins that are particularly sensitive to oxidative damage.

Serotonin transporter (5-HTTLPR) genotypes and trinucleotide repeats of androgen receptor exert a combinatorial effect on hormonal milieu in patients with lifelong premature ejaculation.

Premature ejaculation is one of the most common sexual disorders in men due to uncontrolled modulation of spinal reflexes controlled by cortico-limbic centers in the brain. In this study, we investigate the combinatorial effects of trinucleotide repeats of androgen receptor and allelic variants of the 5-HTTLPR gene on sex steroids, hypophyseal hormones, sexual performance, and premature ejaculation assessment parameters among evidence-based lifelong premature ejaculation subjects. A total of 271 outpatients (age 26.6 ± 1.9) consulting for evidence-based lifelong premature ejaculatory dysfunction were selected in this study. The control group consists of 155 men with normal IELT (>4 min). The study revealed that the subjects who have the highest (≥26) CAG stretches depicted a significantly higher serum oxytocin levels (102.1 pg/ml; n = 126, p < 0.001) compared with the control group (71.2 pg/ml; n = 75, p = <0.001) and patients which have medium (22-25) and short (≤21) CAG stretches (76.63 ng/ml; n = 64, p < 0.001 vs. 77.4 ng/ml; n = 81, p < 0.001). Almost 33 (26.1%) lifelong premature ejaculatory patients had AR variant of longer (≥26) CAG repeats was homozygous for S alleles (SS), 45 (35.7%) was homozygous for L allele (LL), and 48 (38%) had the L/S or S/L genotype of 5-HTTLPR gene. Homozygous (SS) alleles have a significant positive correlation (r = 0.44, p < 0.0001) with the high score of BDI-II (39.1, n = 126, p < 0.001). However, LL alleles have shown a significant positive correlation with PEDT (r = 0.46, p < 0.001) and negative correlation with self-estimated IELT and intercourse satisfaction (r = -0.35, p < 0.001). The innovative study design elaborates that androgen receptor trinucleotide repeats and 5-HTTLPR genotypes have combinatorial impact on hormonal milieu and sexual function regarding evidence-based lifelong premature ejaculatory dysfunction patients.

Serotonergic polymorphisms in the control of ejaculation.

Serotonin has long been implicated in the regulation of the processes that trigger the ejaculatory reflex. Most evidence of serotonergic involvement is, however, indirect, stemming either from studies on rodents or clinical trials investigating effects of serotonergic drugs. In the past decade, emerging evidence for heritability (i.e., genetic effects) of premature ejaculation (PE) symptoms has spawned a number of scholarly attempts to identify genes that regulate ejaculation, most of which have focused on candidate genes related to the serotonergic system. The aim of the present review article was to summarize the literature concerning genetic association studies of PE, with focus on serotonergic genes. However, methodological obstacles relating to the candidate gene approach predict that a priori hypotheses regarding candidate genes are likely to generate ambiguous and spurious results if samples (e.g., if samples are underpowered and/or stratified). Attempts to replicate reported novel associations between PE symptoms and serotonergic candidate genes have largely failed (thereby adding to the growing body of evidence casting doubt on the reliability of the candidate gene approach), and at present, it is not possible to determine with acceptable certainty which serotonergic genes, if any, are involved in ejaculatory function.

Study of the link between dopamine transporter gene polymorphisms and response to paroxetin and escitalopram in patients with lifelong premature ejaculation.

We evaluated the role of dopamine (DA) transporter gene polymorphism in lifelong premature ejaculation (LPE) and its role in determining the response to paroxetine and escitalopram. Eighty consecutive patients and controls were recruited. Sixty of them suffered from LPE. They were divided into two equal groups. One group received paroxetine 20 mg daily for 3 months and the other one received ecistalopram 20 mg daily for 3 months. Their wives were instructed to measure the intra-vaginal ejaculation latency time using stopwatch. Five milliliters of blood was withdrawn from patients and controls for PCR analysis. The present study revealed that the mean ages of the patients and controls were 41.42 and 36.4 years, respectively. The majority of the patients were of (10R/10R) genotypes of the DA transporter gene polymorphism, whereas the controls were of (6R/6R) genotypes and this revealed statistically significant result (P-value=0.001). Both paroxitine and escitalopram significantly delayed ejaculation in the responders (P-values=0.001 and 0.001, respectively). The study revealed significant association between such response and DA transporter gene polymorphism (P-values of fold increase and log FI were 0.019 and 0.010, respectively). To the best of our knowledge, this is the first report to demonstrate a highly significant association between such response and DA transporter gene polymorphism in patients with LPE.

Prostatic urethra malformation associated with retrograde ejaculation: a case report.

BACKGROUND: Retrograde ejaculation can have anatomical, neurogenic, or pharmacological causes. Among these factors, malformation of the prostatic urethra is an uncommon cause. CASE PRESENTATION: We describe a 29-year-old Han Chinese man with absence of his verumontanum combined with ejaculatory duct cysts, and no other cause for ejaculatory dysfunction. His verumontanum was replaced by a deep groove adjacent to his bladder neck, which could significantly influence bladder neck contraction. In addition, the large cysts in the ejaculatory duct could obstruct the anterior outlet of his prostatic urethra and prevent seminal fluid flow in an anterograde direction. There are few reports of retrograde ejaculation associated with congenital malformations of the posterior urethra. Malformations associated with bladder neck laxity and increased tone of the prostatic urethral outlet can contribute to retrograde ejaculation. CONCLUSIONS: Malformation of the prostatic urethra is an uncommon cause of retrograde ejaculation, and can be difficult to treat.

Differential organization of male copulatory patterns in high- and low-yawning-frequency sublines versus outbred Sprague-Dawley rats.

The temporal organization of masculine sexual behavior in rats is highly stereotyped; involving a sequence of mounts, intromissions and ejaculations. Sexual behavior has been described in exogamic and genetically manipulated rodent species. In this work, we compare the male sexual behavior of outbred Sprague-Dawley (SD) to those of rats inbred for high (HY)- and low (LY)- spontaneous yawning frequency. In the first experiment, the percentage of inexperienced rats' ejaculatory behavior is significantly lower in the HY and LY respect to Sprague-Dawley rats. The latency to ejaculate for inexperienced HY was shorter than the LY and SD rats. In the second experiment, we examined the differences between inbred sublines and Sprague-Dawley rats once the subjects had become sexually experienced after four copulatory sessions. HY rats still have slower proportion of ejaculators respect to LY and SD rats. Additionally, postejaculatory latencies were longer for HY rats, with longer intercopulatory intervals and higher number of copulatory bouts that delayed ejaculation. Both sublines show lower copulatory efficiency respect to SD rats. In conclusion, both sublines show alterations in the temporal organization of sexual motor pattern that are due at least partially to strong inbreeding process to select them.

The 5-HT2C receptor gene Cys23Ser polymorphism influences the intravaginal ejaculation latency time in Dutch Caucasian men with lifelong premature ejaculation.

It has been postulated that the persistent short intravaginal ejaculation latency time (IELT) of men with lifelong premature ejaculation (LPE) is related to 5-hydroxytryptamine (HT)2C receptor functioning. The aim of this study was to investigate the relationship of Cys23Ser 5-HT2C receptor gene polymorphism and the duration of IELT in men with LPE. Therefore, a prospective study was conducted in 64 Dutch Caucasian men with LPE. Baseline IELT during coitus was assessed by stopwatch over a 1-month period. All men were genotyped for Cys23Ser 5-HT2C receptor gene polymorphism. Allele frequencies and genotypes of Cys and Ser variants of 5-HT2C receptor gene polymorphism were determined. Association between Cys/Cys and Ser/Ser genotypes and the natural logarithm of the IELT in men with LPE were investigated. As a result, the geometric mean, median and natural mean IELT were 25.2, 27.0, 33.9 s, respectively. Of all men, 20.0%, 10.8%, 23.1% and 41.5% ejaculated within 10, 10-20, 20-30 and 30-60 s after vaginal penetration. Of the 64 men, the Cys/Cys and Ser/Ser genotype frequency for the Cys23Ser polymorphism of the 5-HT2C receptor gene was 81% and 19%, respectively. The geometric mean IELT of the wildtypes (Cys/Cys) is significantly lower (22.6 s; 95% CI 18.3-27.8 s) than in male homozygous mutants (Ser/Ser) (40.4 s; 95% CI 20.3-80.4 s) (P = 0.03). It is concluded that Cys23Ser 5-HT2C receptor gene polymorphism is associated with the IELT in men with LPE. Men with Cys/Cys genotype have shorter IELTs than men with Ser/Ser genotypes.

Functional equivalence of grasping cerci and nuptial food gifts in promoting ejaculate transfer in katydids.

The function of nuptial gifts has generated longstanding debate. Nuptial gifts consumed during ejaculate transfer may allow males to transfer more ejaculate than is optimal for females. However, gifts may simultaneously represent male investment in offspring. Evolutionary loss of nuptial gifts can help elucidate pressures driving their evolution. In most katydids (Orthoptera: Tettigoniidae), males transfer a spermatophore comprising two parts: the ejaculate-containing ampulla and the spermatophylax-a gelatinous gift that females eat during ejaculate transfer. Many species, however, have reduced or no spermatophylaces and many have prolonged copulation. Across 44 katydid species, we tested whether spermatophylaces and prolonged copulation following spermatophore transfer are alternative adaptations to protect the ejaculate. We also tested whether prolonged copulation was associated with (i) male cercal adaptations, helping prevent female disengagement, and (ii) female resistance behavior. As predicted, prolonged copulation following (but not before) spermatophore transfer was associated with reduced nuptial gifts, differences in the functional morphology of male cerci, and behavioral resistance by females during copulation. Furthermore, longer copulation following spermatophore transfer was associated with larger ejaculates, across species with reduced nuptial gifts. Our results demonstrate that nuptial gifts and the use of grasping cerci to prolong ejaculate transfer are functionally equivalent.

Ejaculados individuais e pools de sêmen: diferenças em condições experimentais / Individual ejaculates and pooled semen: differences under experimental conditions

Avaliaram-se ejaculados caninos individuais e pools de sêmen submetidos a dois tratamentos de renovação do meio diluidor. Sêmen de seis cães foi coletado, na forma de ejaculados individuais e pools de sêmen, diluído na proporção de 1:1 em meio Tris-Gema, centrifugado a 500g/10min, e o pellet ressuspendido até concentração final de 50x10(6) espermatozoides/mL. O sêmen foi resfriado a 0,26ºC/min, entre 37 e 16ºC, e 0,08ºC/min, entre 16 a 8ºC, e mantido em geladeira a 5ºC por 14 dias. No Tratamento 1, o meio diluidor foi renovado a cada seis dias, e no Tratamento 2 aos 12 dias. O sêmen foi avaliado, a cada 48 horas, quanto à motilidade espermática, utilizando-se o Sperm Class Analyser® (SCA), e quanto à integridade de membranas pelo teste hiposmótico e coloração com PI/CFDA. A formação de pools de sêmen simplificou sua manipulação, principalmente com relação ao aumento do volume da amostra disponível; no entanto, resultados obtidos a partir de ejaculados individuais mostraram diferenças entre tratamentos, não identificadas nos pools de sêmen.

Individual ejaculates and pooled dog semen submitted to two treatments of medium exchange were evaluated. Semen was collected from six dogs, as individual ejaculates and pooled semen, diluted in a 1:1 ratio in Tris-Yolk medium, centrifuged at 500g/10min and ressuspended to the final concentration of 50x10(6) sptz/mL. The samples were cooled at rates of 0.26 o C/min between 37 and 16 o C, and 0.08ºC/min from 16 to 8ºC, and then kept in a refrigerator for 14 days. In Treatement 1 medium was exchanged every six days and in Treatment 2 after twelve days. The cooled samples were evaluated every 48 hours for sperm motility using the Sperm Calss Analyser® (SCA), and membrane integrity with hiposmotic swelling test and PI/CFDA stain. Pooled semen was easier to handle, mainly considering the decreased work due to volume. When submitted to medium exchange, pooled semen behaved similarly to individual ejaculates; however, results obtained from individual ejaculates showed differences between treatments, which were not apparent in pooled semen results.

Genetic disruption of the copulatory plug in mice leads to severely reduced fertility.

Seminal fluid proteins affect fertility at multiple stages in reproduction. In many species, a male's ejaculate coagulates to form a copulatory plug. Although taxonomically widespread, the molecular details of plug formation remain poorly understood, limiting our ability to manipulate the structure and understand its role in reproduction. Here I show that male mice knockouts for transglutaminase IV (Tgm4) fail to form a copulatory plug, demonstrating that this gene is necessary for plug formation and lending a powerful new genetic tool to begin characterizing plug function. Tgm4 knockout males show normal sperm count, sperm motility, and reproductive morphology. However, very little of their ejaculate migrates into the female's reproductive tract, suggesting the plug prevents ejaculate leakage. Poor ejaculate migration leads to a reduction in the proportion of oocytes fertilized. However, Tgm4 knockout males fertilized between 3-11 oocytes, which should be adequate for a normal litter. Nevertheless, females mated to Tgm4 knockout males for approximately 14 days were significantly less likely to give birth to a litter compared to females mated to wild-type males. Therefore, it appears that the plug also affects post-fertilization events such as implantation and/or gestation. This study shows that a gene influencing the viscosity of seminal fluid has a major influence on male fertility.

Clinical value of sperm DNA damage should be assessed in motile sperm fraction rather than whole ejaculated sperm.

OBJECTIVE: To determine differences and frequency of excessive (≥50%) sperm DNA damage between ejaculated and motile sperm. DESIGN: Sperm DNA damage was assessed by acridine orange fluorescence and the results of ejaculated and motile sperm were compared. SETTING: Public and private clinical assisted reproduction centers. PATIENT(S): A total of 272 subfertile men were studied. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Semen analysis and sperm DNA damage. RESULT(S): Sperm DNA damage was negatively correlated with sperm motility and normal morphology. Overall, 39.7% (108 of 272) of semen samples had excessive sperm DNA damage. In contrast, only 15% (41 of 272) of motile sperm fractions had excessive DNA damage. Based on DNA results of motile sperm and semen characteristics, the proportion of men with excessive sperm DNA damage was 26% in severe teratozoospermia, 17.5% in oligozoospermia, 12.5% in moderate teratozoospermia, and 4.6% in normozoospermia. Severe teratozoospermia had five times more frequent excessive DNA damage than normozoospermia. CONCLUSION(S): Abnormal sperm morphology is highly associated with sperm DNA damage. Results of DNA damage of ejaculated sperm do not accurately reflect DNA status of motile sperm. Therefore, sperm DNA damage should be assessed in motile sperm fraction rather than whole ejaculated sperm.

Are single nucleotide polymorphisms in the oxytocin and vasopressin 1A/1B receptor genes likely candidates for variation in ejaculatory function?

UNLABELLED: What's known on the subject? and What does the study add? There is also evidence that the etiology of premature ejaculation is partially genetic. So far, all molecular genetic studies of premature ejaculation have focused on serotonergic and dopaminergic genes. Serotonergic and dopaminergic neurotransmission aside, studies on both animals and humans have shown that both oxytocin and vasopressin are also involved in ejaculatory function. The present study is, to our knowledge, the first to investigate effects of polymorphisms in oxytocin and vasopressin receptor genes on ejaculatory function. Although a large sample (1517 men) was available for the present study, we could not detect any clear-cut effects of any gene variant on ejaculatory function. We detected a heterozygote effect of one polymorphism (rs75775) in the oxytocin receptor gene. Rare variants of the vasopressin receptor 1A gene may theoretically have a stronger impact on ejaculatory function, but would need a very large sample in order to be established. Based on our results, we conclude that the oxytocin and vasopressin receptor genes are unlikely targets for successful pharmacogenetic interventions. OBJECTIVES: • To investigate associations between single nucleotide polymorphisms (SNPs) linked to the oxytocin, and arginine vasopressin 1A and 1B receptor genes and ejaculatory function. • To investigate these associations in a large, population-based sample. PATIENTS AND METHODS: • In all, 1517 male twins and non-twin brothers of twins aged 18-45 years (mean = 26.43; sd = 4.87) provided questionnaire data regarding ejaculatory function and relevant covariates and saliva samples for genotyping. • A Bayesian linear mixed-effects model, which appropriately controls for between-subjects dependence, was used to estimate genotype associations. • We corrected for multiple testing using a linkage disequilibrium correlation measure. RESULTS: • We found a heterozygote effect on one SNP in the oxytocin receptor gene (rs75775), so that individuals heterozygous for this SNP had significantly elevated risk for premature ejaculation symptoms compared with carriers of either homozygote. • Several SNPs in the arginine vasopressin receptor genes had rare or very rare genotypes. This study may be underpowered to detect potential effects of rare genotypic variants in arginine vasopressin receptor genes. CONCLUSIONS: • Our results regarding the oxytocin receptor polymorphisms support previous studies that indicate a complex relationship between oxytocin and ejaculatory function. • Oxytocin receptor genes are, for example, unlikely suitable targets for pharmacogenetic intervention studies. • Rare variants in arginine vasopressin receptor genes may have significant effects on premature ejaculation, but would need larger sample sizes or case-control designs to be detected.

A study of possible associations between single nucleotide polymorphisms in the serotonin receptor 1A, 1B, and 2C genes and self-reported ejaculation latency time.

INTRODUCTION: Previous research has indicated that serotonergic genes may influence ejaculatory function. Attempts to investigate effects of polymorphisms in serotonergic genes have been carried out, but so far, no study has conducted exploratory genotype analyses regarding the serotonin receptor 1A, 1B, and 2C subtypes, which have been hypothesized to mediate the inhibitory effects of serotonin on ejaculation in rodents. AIM: The aim of the present study was to investigate effects of a total of six single nucleotide polymorphisms (SNPs) located in genes encoding serotonin receptor subtypes 1A, 1B, and 2C on self-reported ejaculation latency time. METHODS: A retrospective self-report measure of ejaculation latency time was used to investigate ejaculatory function in a population-based sample of 1,399 male twins. DNA was collected using self-administered saliva sampling. MAIN OUTCOME MEASURE: Calculations of allelic effects were conducted using the Generalized Estimating Equations module of PASW 18.0, which appropriately controls for between-subjects dependence. RESULTS: Out of six investigated polymorphisms, two SNPs (both serotonin receptor 5-HT(1B) linked) had a significant main effect on ejaculation latency time. Of these, one (rs11568817) remained significant after Bonferroni correction for multiple testing, indicating that individuals homozygous for the G allele had significantly shorter ejaculation latencies. CONCLUSIONS: The results of this study support the hypothesis that serotonergic genes play a role in ejaculatory function in the general population. Replication of the results of the present study is warranted.

[Study on the correlation of the 5-HTTLPR polymorphism with premature ejaculation in Han Chinese population].

OBJECTIVE: To investigate the relationship between 5-HT transporter gene-linked polymorphism (5-HTTPLR) and the clinical characters of premature ejaculation in Han Chinese population. METHODS: By case-control study approach, we set primary premature ejaculation (PPE) group (119 cases), secondary premature ejaculation (SPE) group (60 cases) with IELT < 1 min in more than 90% coitus and normal control group (90 cases) with IELT ≥ 3 min. The gene polymorphism of the 5-HTT was detected by polymerase chain reaction analysis in all the cases, and the gene frequency differences among the three groups were evaluated. RESULTS: The frequency of the genotype S/S was higher in PPE group than in normal control group(51.3% vs. 37.8%,P<0.01), and the frequency of genetype L/S was lower in PPE group than in normal vontrol group(28.6% vs. 34.4%,P<0.05).The S allele was higher in PPE group than in control group (P<0.05), but there was no difference between the SPE group and the normal control group. CONCLUSION: The 5-HTTLPR polymorphism is associated with PPE, which shows that genetics may play an important role in the occurrence of PPE but not of SPE. The etiology of PPE and SPE is different.

Relationship between premature ejaculation and genetic polymorphisms of the dopamine transporter gene (SLC6A3).

OBJECTIVE: • To investigate the possible relationships between premature ejaculation (PE) polymorphisms in the dopamine transporter (DAT) gene (SLC6A3, DAT1), which has a polymorphic 40 base pair (40 bp) variable number of tandem repeats (VNTR) sequence in the 3'-untranslated region (3' VNTR). PATIENTS AND METHODS: • Cohorts of 270 Iranian men with PE and 266 age-matched healthy Iranian subjects were genotyped for the DAT1-VNTR polymorphism. RESULTS: • The 10-repeat allele frequencies were similar in the control (90.2%) and patient groups (88.5%) (P = 0.8). • A statistically significant association was observed between the presence of the nine-repeat allele and PE (chi-squared test = 4.346, odds ratio [OR] = 2.46, 95% confidence interval [CI] = 1.57-3.15, P = 0.026). • The frequencies of the 9/10 genotype were also significantly higher in the PE patients than in normal controls (chi-squared test = 4.466, OR = 2.47, 95% CI = 1.52-3.21, P = 0.028). The presence of the seven-repeat allele had a protective effect against PE (chi-squared test = 2.324, OR = 0.62, 95% CI = 0.47-0.89, P = 0.034). CONCLUSIONS: • The findings of the present study suggest that DAT1-VNTR polymorphisms resulting in higher dopamine concentrations were associated with vulnerability to PE. • Further studies are needed to replicate these results and to evaluate the role of inconsistency in the DAT genes and how this affects the development of PE.

Association between polymorphisms in the serotonin 2C receptor gene and premature ejaculation in Han Chinese subjects.

INTRODUCTION: Lifelong premature ejaculation (LPE) is characterized by persistently shorter intravaginal ejaculation latency time (IELT) than found acceptable by the patient or his partner. It has been postulated to be a neurobiological dysfunction with genetic vulnerability and is related to disturbances of central serotonin (5-hydroxytryptamine, 5-HT) neurotransmission and 5-HT receptor function. AIM: To investigate the relationship between the C-759T and G-697C polymorphisms of the 5-HT(2C) receptor and LPE. METHODS: A prospective study was conducted in 106 Han Chinese men with LPE, characterized by IELT of less than 1 min, and 84 healthy controls with IELT of more than 3 min. All subjects were genotyped for the C-759T and G-697C polymorphisms located in the promoter region of the 5-HT(2C) receptor. The frequencies of genotypes and single nucleotide mutations were compared between the two groups. RESULTS: Three genotypes were detected both in the men with LPE and in the control group: -759C/-697G, -759T/-697C, and -759C/ -697C. Genotype -759T/-697G was not detected. The frequency of genotype -759T/-697C was higher in patients with LPE than in the control group (30.2 vs. 11.9%, p < 0.05), whereas the frequency of genotype -759C/-697G was lower in patients with LPE than in the control group (66.0 vs. 83.3%, p < 0.05). No difference was found for genotype -759C/ -697C between the two groups. Mutations at -759T and -697C were more frequent in patients than in the control group (-759T: 30.2 vs. 13.3%, p < 0.05; -697C: 30.4 vs. 16.7%, p < 0.05, respectively). CONCLUSIONS: Our findings indicated that polymorphisms in the 5-HT(2C) receptor gene are associated with LPE, and men who carry the -759T or -697C genotype have increased odds of premature ejaculation. Further investigation in this field is necessary.

The dopamine transporter gene (DAT1) polymorphism is associated with premature ejaculation.

INTRODUCTION: Previous research has suggested brain dopamine (DA) neurotransmission to be involved in the control of ejaculation. Furthermore, previous studies indicate a partly hereditary background to premature ejaculation. AIM: To investigate whether the dopamine transporter gene (DAT1) polymorphism is associated with premature ejaculation. METHODS: Retrospective self-reports of four indicators reflecting ejaculatory function-anteportal ejaculation, number of penile thrusts, ejaculation latency time, and feeling of control over ejaculation-and saliva samples for DNA analysis were obtained from 1,290 men (M = 26.9, standard deviation = 4.7 years; range 18-45) with sexual experience. Main Outcome Measures. Calculations of allelic effects were computed using the Generalized Estimating Equations module of SPSS 17. RESULTS: Carriers of the 10R10R genotype had scores indicating a lower threshold to ejaculate on each of the indicators compared to the combined 9R9R/9R10R carrier group. The differences were significant both for the composite score and for anteportal ejaculation, number of thrusts, and feeling of control over ejaculation, but not for ejaculation latency time. The effect of the polymorphism remained significant after controlling for age, homosexual experience, having a regular sexual partner, level of sexual desire, and frequency of sexual activity, hence suggesting that it is not secondary to an association between the studied polymorphism and some other aspect of sexual behavior, but due to a specific influence of DA on ejaculation. CONCLUSIONS: The findings of the present study support results of previous studies indicating involvement of dopaminergic neurotransmission in ejaculation.