Asian Journal of Andrology,China

To investigate the factors affecting the sperm retrieval rate of microdissection testicular sperm extraction (micro-TESE) in patients with nonmosaic Klinefelter syndrome (KS), 64 patients with nonmosaic KS who underwent micro-TESE in the Center for Reproductive Medicine of Peking University Third Hospital (Beijing, China) between January 2016 and December 2017 were included in the study. Data on medical history, physical examination and laboratory examination results, and micro-TESE outcomes were collected. Patients were divided into two groups according to micro-TESE outcomes. The following factors were compared between the two groups by the Mann-Whitney U test or Student’s t-test based on the distribution (nonnormal or normal) of the factors: age, testicular size, follicle-stimulating hormone level, luteinizing hormone level, testosterone level, and anti-Müllerian hormone level. The overall success rate of sperm retrieval was 50.0%. Correlation analysis showed that testicular volume was positively correlated with testosterone level. Using a logistic regression model, age and anti-Müllerian hormone levels were found to be better predictors for the sperm retrieval rate than the other parameters.

As a specific type of asthenoteratozoospermia, multiple morphological abnormalities of the sperm flagella (MMAF) is characterized by composite abnormalities, including absent, short, coiled, angulation, and irregular-caliber flagella. Mutations in cilia- and flagella-associated protein 43 (CFAP43) are one of the main causative factors of MMAF established to date. To identify whether there are other CFAP43 mutations related to MMAF and to determine the clinical outcomes of assisted reproductive technology for patients with MMAF harboring different mutations, we recruited and screened 30 MMAF-affected Chinese men using a 22-gene next-generation sequencing panel. After systematic analysis, seven mutations in CFAP43, including five novel mutations and two previously reported mutations, were identified from four families and related to MMAF in an autosomal recessive pattern. Papanicolaou staining, immunofluorescence, and electronic microscopy further clarified the semen characteristics and abnormal sperm morphologies, including disorganized axonemal and peri-axonemal structures, of the CFAP43-deficient men. The female partners of two patients were pregnant after undergoing assisted reproductive technology through intracytoplasmic sperm injection, and one of them successfully gave birth to a healthy boy. This study significantly expands the mutant spectrum of CFAP43, and together with the available information regarding male infertility and MMAF, provides new information for the genetic diagnosis and counseling of MMAF in the future.

Male infertility is a major reproductive disorder, which is clinically characterized by highly heterogeneous phenotypes of abnormal sperm count or quality. To date, five male patients with biallelic loss-of-function (LOF) variants of PARN-like ribonuclease domain-containing exonuclease 1 (PNLDC1) have been reported to experience infertility with nonobstructive azoospermia. The aim of this study was to identify the genetic cause of male infertility with oligo-astheno-teratozoospermia (OAT) in a patient from a Chinese Han family. Whole-exome and Sanger sequencing analyses identified a homozygous LOF variant (NM_173516.2, c.142C>T, p.Gln48Ter) in PNLDC1. Hematoxylin and eosin staining revealed that the spermatozoa of the patient with OAT had an irregular head phenotype, including microcephaly, head tapering, and globozoospermia. Consistently, peanut agglutinin staining of the spermatozoa revealed a complete or partial loss of the acrosome. Furthermore, the disomy rate of chromosomes in the patient’s spermatozoa was significantly increased compared with that of a fertile control sample. We reported an LOF variant of the PNLDC1 gene responsible for OAT.

Approximately 31% of patients with 22q11.2 deletion syndrome (22q11.2DS) have genitourinary system disorders and 6% of them have undescended testes. Haploinsufficiency of genes on chromosome 22q11.2 might contribute to the risk of 22q11.2DS. In this study, we used mice with single-allele deletion in mitochondrial ribosomal protein L40 (Mrpl40^+/−) as models to investigate the function of Mrpl40 in testes and spermatozoa development. The penetrance of cryptorchidism in Mrpl40^+/− mice was found to be higher than that in wild-type (WT) counterparts. Although the weight of testes was not significantly different between the WT and Mrpl40^+/− mice, the structure of seminiferous tubules and mitochondrial morphology was altered in the Mrpl40^+/− mice. Moreover, the concentration and motility of spermatozoa were significantly decreased in the Mrpl40^+/− mice. In addition, data-independent acquisition mass spectrometry indicated that the expression of genes associated with male infertility was altered in Mrpl40^+/− testes. Our study demonstrated the important role of Mrpl40 in testicular structure and spermatozoa motility and count. These findings suggest that Mrpl40 is potentially a novel therapeutic target for cryptorchidism and decreased motility and count of spermatozoa.

We examined a cohort of 93 cystic fibrosis (CF) male patients who were pancreatic-sufficient (PS-CF; n=40) or pancreatic-insufficient (PI-CF; n = 53). Complex semen examination was performed, including standard semen analysis, quantitative karyological analysis (QKA) of immature germ cells (IGCs), transmission electronic microscopy (TEM), biochemical analysis, and sperm DNA fragmentation by terminal deoxynucleotidyl transferase-mediated dUTP nickend labeling (TUNEL) assay. Azoospermia was diagnosed in 83 (89.2%) patients. The other 10 (10.8%) patients were found to be nonazoospermic and showed various spermatological diagnoses (asthenozoospermia, n = 2; asthenoteratozoospermia, n = 3; oligoasthenozoospermia, n = 1; oligoasthenoteratozoospermia, n = 3; and normozoospermia, n = 1) with no specific morphological abnormalities. Oligospermia was detected in 89.2% azoospermic and 30.0% nonazoospermic patients. Low seminal pH (30%) of spermatozoa with noncondensed (“immature”) chromatin was revealed in 2 of 6 nonazoospermic semen samples analyzed by TEM.

Accumulating evidence has revealed many clues that regular aerobic exercise benefits brain health and behaviors. The aims of this study were to explore the effect of aerobic exercise on ejaculatory behaviors, as well as to make a preliminary assessment of aerobic exercise as a complementary strategy to dapoxetine treatment in rapid ejaculators. Copulatory tests of rats and a treadmill training protocol were performed in this study. In total, 12 rapid ejaculators were selected on the basis of ejaculation distribution theory and randomly assigned to 4 groups: control (Ctrol) group, aerobic exercise (Ex) group, dapoxetine (Dapo) group, and Ex+Dapo group. We evaluated the changes in ejaculatory parameters in the 4 groups. Variations in biological markers, including serum corticosterone, serotonin (5-HT), and brain-derived neurotrophic factor (BDNF) of the raphe nucleus, were determined by enzyme-linked immunosorbent assay (ELISA). The primary finding of our study was that both aerobic exercise and acute dapoxetine could enhance ejaculation control and prolong ejaculation latency in rapid ejaculator rats. The ejaculation delay effect of aerobic exercise was nearly equivalent to that of acute dapoxetine. In addition, both aerobic exercise and dapoxetine treatment could lead to increased expression of BDNF and 5-HT in the raphe nucleus of rapid ejaculators. Moreover, the two interventions, when applied together, may further upregulate the expression of BDNF-5-HT duo in a complementary manner. This study highlights the positive effects of aerobic exercise on ejaculation control. Regular aerobic exercise might be a promising complementary treatment to dapoxetine in rats.

This study aimed to assess the outcomes of modified onlay island flap (MOIF) urethroplasty for hypospadias reoperation. A retrospective analysis was conducted using clinical data on children reoperated with MOIF or tubularized incised plate (TIP) urethroplasty for hypospadias in the Children’s Hospital of Nanjing Medical University (Nanjing, China) from December 2016 to September 2020. A total of 90 children with hypospadias who failed primary repair and were reoperated on with MOIF (MOIF group, n = 46) or TIP urethroplasty (TIP group, n = 44) were recruited. All children were postoperatively followed up for at least 6 months. Six patients with postoperative urinary fistula, 2 patients with glans dehiscence, and 1 patient with urethral diverticulum were reported in the MOIF group, while 7 patients with postoperative urinary fistula, 2 patients with urethral stricture, and 1 patient with glans dehiscence were reported in the TIP group. Postoperative infection, flap necrosis and other complications were not recorded. A total of 37 (80.4%) patients in the MOIF group and 34 (77.3%) patients in the TIP group were successfully reoperated. Although the success rates of MOIF and TIP urethroplasty are comparable, pediatricians should master different types of repair techniques for individualized hypospadias reoperation. MOIF urethroplasty can be recommended after failure of the primary repair.

This study aimed to determine whether the abnormal deep layer of dartos fascia plays an important role in buried penis. Forty-nine patients with buried penis were treated with anatomical resection of the deep layer of dartos fascia under a microscope. Penile length was measured before and after completely resecting the deep layer to investigate the role of this layer in penile retraction. The superficial and deep layers of dartos fascia were collected from 49 patients with buried penis, the normal superficial layers were collected from 25 children/adults who underwent circumcision for nonmedical reasons, and the normal deep layers were collected from 20 adult cadavers. The penile fascia samples were stained with hematoxylin-eosin, Masson’s trichrome, Sirius red, and Verhoeff’s Van Gieson, and subjected to immunohistochemical examination and scanning electron microscopy. The penile shaft (mean ± standard deviation) was found to be significantly elongated after resecting the deep layer compared with that before resection (6.8 ± 1.9 cm vs 6.0 ± 1.6 cm, P < 0.001). An abnormal deep layer of dartos fascia characterized by disordered and fragmented elastic fibers was observed in 87.8% (43/49) of buried penis samples, whereas no abnormal deep layer was observed in normal penises from cadavers (0/20, P < 0.001). Thus, the abnormal deep layer of dartos fascia plays an important role in the buried penis. Its resection is helpful for avoiding recurrence.