Novel variants in DNAH6 cause male infertility associated with multiple morphological abnormalities of the sperm flagella(MMAF)and ICSI outcomes

Variations in the dynein axonemal heavy chain gene,dynein axonemal heavy chain 6(DNAH6),lead to multiple morphological abnormalities of the flagella.Recent studies have reported that these deficiencies may result in sperm head deformation.However,whether DNAH6 is also involved in human acrosome biogenesis remains unknown.The purpose of this study was to investigate DNAH6 gene variants and their potential functions in the formation of defective sperm heads and flagella.Whole-exome sequencing was performed on a cohort of 375 patients with asthenoteratozoospermia from the First Affiliated Hospital of Anhui Medical University(Hefei,China).Hematoxylin and eosin staining,scanning electron microscopy,and transmission electron microscopy were performed to analyze the sperm morphology and ultrastructure.Immunofluorescence staining and Western blot analysis were conducted to examine the effects of genetic variants.We identified three novel deleterious variants in DNAH6 among three unrelated families.The absence of inner dynein arms and radial spokes was observed in the sperm of patients with DNAH6 variants.Additionally,deficiencies in the acrosome,abnormal chromatin compaction,and vacuole-containing sperm heads were observed in these patients with DNAH6 variants.The decreased levels of the component proteins in these defective structures were further confirmed in sperm from patients with DNAH6 variants using Western blot.After intracytoplasmic sperm injection(ICSl)treatment,the partner of one patient with a DNAH6 variant achieved successful pregnancy.Overall,novel variants in DNAH6 genes that contribute to defects in the sperm head and flagella were identified,and the findings indicated Icsl as an effective clinical treatment for such patients.

Validity of premature ejaculation diagnostic tool and its association with International Index of Erectile Function-15 in Chinese men with evidence-based-defined premature ejaculation

The premature ejaculation diagnostic tool （PEDT） is a brief diagnostic measure to assess premature ejaculation （PE）. However, there is insufficient evidence regarding its validity in the new evidence-based-defined PE. This study was performed to evaluate the validity of PEDT and its association with IIEF-15 in different types of evidence-based-defined PE. From June 2015 to January 2016, a total of 260 men complaining of PE and defined as lifelong PE （LPE）/acquired PE （APE） according to the evidence-based definition from Andrology Clinic of the First Affiliated Hospital of Anhui Medical University, along with 104 male healthy controls without PE from a medical examination center, were enrolled in this study. All individuals completed questionnaires including demographics, medical and sexual history, as well as PEDT and IIEF-15. After statistical analysis, it was found that men with PE reported higher PEDT scores （14.28 ± 3.05） and lower IIEF-15 （41.26 ± 8.20） than men without PE （PEDT： 5.32 ± 3.42, IIEF-15：52.66 ± 6.86, P 〈 0.001 for both）. It was suggested that a score of 〉9 indicated PE in both LPE and APE by sensitivity and specificity analyses （sensitivity： 0.875, 0.913; specificity： 0.865, 0.865, respectively）. In addition, IIEF-15 were higher in men with LPE （42.64 ± 8.11） than APE （39.43 ± 7.84, P 〈 0.001）. After adjusting for age, IIEF-15 was negatively related to PEDT in men with LPE （adjust r = -0.225, P 〈 0.001） and APE （adjust r = -0.378, P 〈 0.001）. In this study, we concluded that PEDT was valid in the diagnosis of evidenced-based-defined PE. Furthermore, IIEF-15 was negatively related to PEDT in men with different types of PE.

Association between polymorphisms in the human serotonin transporter gene and lifelong premature ejaculation in the Han population

Dear Editor, Lifelong premature ejaculation （LPE） is a type of sexual dysfunction in males and has three characteristics： （1） an intravaginal ejaculatory latency time （IELT） of 〈 1 rain; （2） insufficient control over delaying ejaculation; and （3） negative personal consequences, such as distress, frustration, and/or the avoidance of sexual intimacy2 Its etiologies involve the 5-hydroxytryptamine （5-HT） system. The use of 5-HT transporter （5-HTT） blockers （e.g., selective serotonin reuptake inhibitors, SSRIs） was found to prevent the reuptake of 5-HT from the synaptic cleft into the presynaptic serotonergic neurons, which leads to increased extracellular 5-HT levels, thereby delaving ejaculation.