Basic and Clinical Andrology最新文献

Introduction: Nicotinamide nucleotide transhydrogenase (NNT) gene deficiency has recently been shown to be involved in Primary Adrenal Insufficiency (PAI). NNT encodes an inner mitochondrial membrane protein that produces large amounts of NADPH. NADPH is used in several biosynthesis pathways and the oxidoreduction of free radicals by the glutathione and thioredoxin systems in mitochondria. Patients with PAI due to NNT deficiency may also exhibit extra-adrenal manifestations, usually including gonadal impairment.

Case report: We present the case of a 35-year-old patient referred to our center for primary infertility with non-obstructive azoospermia, in a context of PAI and obesity. PAI genetic exploration carried out at the age of thirty revealed NNT deficiency due to the presence of two deleterious mutations (one on each allele) in the NNT gene. Scrotal ultrasound revealed a right Testicular Adrenal Rest Tumor (TART). Intensification of glucocorticoid therapy over the course of 8 months failed to reduce the TART volume or improve sperm production and endocrine function. No spermatozoa were found after surgical exploration of both testes, and subsequent histopathological analysis revealed bilateral Sertoli cell-only syndrome. A retrospective review of the hypothalamic-pituitary-gonadic axis hormonal assessment over 20 years showed progressive impairment of testicular function, accelerated during adulthood, leading to hypergonadotropic hypogonadism and non-obstructive azoospermia when the patient reached his thirties, while the PAI remained controlled over the same period.

Conclusion: This case report provides, for the first time, direct evidence of complete germ line loss in an azoospermic man with NNT deficiency. Additional data further support the hypothesis of a determinant role of oxidative cellular damage due to reactive oxygen species (ROS) imbalance in the severe gonadal impairment observed in this NNT-deficient patient. Early and regular evaluation of gonadal function should be performed in patients with PAI, especially with NNT deficiency, as soon as the patients reach puberty. Fertility preservation options should then be provided in early adulthood for these patients.

Background: Coronavirus disease 2019 (COVID-19) has spread rapidly worldwide since its discovery in December 2019. Research published since the COVID-19 outbreak has focused on whether semen quality and reproductive hormone levels are affected by COVID-19. However, there is limited evidence on semen quality of uninfected men. This study aimed to compare semen parameters among uninfected Chinese sperm donors before and after the COVID-19 pandemic to determine the impact of the COVID-19 pandemic-related stress and lifestyle changes on uninfected men.

Results: All semen parameters were non-significant except semen volume. The average age of sperm donors was higher after the COVID-19 (all P < 0.05). The average age of qualified sperm donors increased from 25.9 (SD: 5.3) to 27.6 (SD: 6.0) years. Before the COVID-19, 45.0% qualified sperm donors were students, but after the COVID-19, 52.9% were physical laborers (P < 0.05). The proportion of qualified sperm donors with a college education dropped from 80.8 to 64.4% after the COVID-19 (P < 0.05).

Conclusion: Although the sociodemographic characteristics of sperm donors changed after the COVID-19 pandemic, no decline in semen quality was found. There is no concern about the quality of cryopreserved semen in human sperm banks after the COVID-19 pandemic.

Spermatogenesis is the process of generation of male reproductive cells from spermatogonial stem cells in the seminiferous epithelium of the testis. During spermatogenesis, key spermatogenic events such as stem cell self-renewal and commitment to meiosis, meiotic recombination, meiotic sex chromosome inactivation, followed by cellular and chromatin remodeling of elongating spermatids occur, leading to sperm cell production. All the mentioned events are at least partially controlled by the epigenetic modifications of DNA and histones. Additionally, during embryonal development in primordial germ cells, global epigenetic reprogramming of DNA occurs. In this review, we summarized the most important epigenetic modifications in the particular stages of germ cell development, in DNA and histone proteins, starting from primordial germ cells, during embryonal development, and ending with histone-to-protamine transition during spermiogenesis.

Background: The coronavirus disease 2019 (COVID-19) outbreak has had a widespread and profound impact on people's mental health. The factors associated with mental symptoms among men diagnosed with infertility, a disease closely related to psychological conditions, remain unclear. The aim of this study is to investigate the risk factors associated with mental symptoms among infertile Chinese men during the pandemic.

Results: A total of 4,098 eligible participants were recruited in this cross-sectional, nationwide study, including 2,034 (49.6%) with primary infertility and 2,064 (50.4%) with secondary infertility. The prevalence of mental health conditions was 36.3%, 39.6%, and 6.7% for anxiety, depression, and post-pandemic stress, respectively. Sexual dysfunction is associated with a higher risk with adjusted odds ratios (ORs) of 1.40 for anxiety, 1.38 for depression, and 2.32 for stress. Men receiving infertility drug therapy displayed a higher risk for anxiety (adjusted OR, 1.31) and depression (adjusted OR, 1.28) symptoms, while those receiving intrauterine insemination had a lower risk of anxiety (adjusted OR, 0.56) and depression (adjusted OR, 0.55) symptoms.

Conclusion: The COVID-19 pandemic has had a significant psychological impact on infertile men. Several psychologically vulnerable populations were identified, including individuals with sexual dysfunction, respondents receiving infertility drug therapy, and those experiencing control measures for COVID-19. The findings provide a comprehensive profile of the mental health status of infertile Chinese men during the COVID-19 outbreak and provide potential psychological intervention strategies.

Background: Despite the documented effects of the coronavirus disease 2019 (COVID-19) on spermatogenesis, the reversibility of these effects is uncertain. We aimed to assess the changes of sperm quality between the infection and recovery phases of COVID-19 in reproductive-aged men. The semen quality of men with mild-to-moderated COVID-19 (defined by the degrees of symptoms and chest involvement on computed tomography) was studied during October, 2020-May, 2021 at our hospital. Two semen samples were analyzed at timings estimated to represent spermatogenic cycles during the infection and recovery phases of COVID-19.

Results: A total of 100 patients were included with mean ± SD (range) age of 24.6 ± 3.3 (21-35) years. During infection, 33% of patients had abnormal semen quality. However, a significant reduction was found in this abnormality from 33 to 11% (P < 0.001) after recovery from infection. In a comparison of the two semen analyses, there were significant improvements in the mean values of sperm progressive motility (P =0.043) and normal morphology (P < 0.001). However, the mean sperm concentration showed a statistically insignificant increase (P = 0.844).

Conclusions: In reproductive-aged patients with mild-to-moderate COVID-19, the effects on seminal quality were recoverable, represented by significant improvements in the means of progressive sperm motility and normal morphology between the infection and recovery phases of COVID-19.

Trial registration: ClinicalTrials, NCT04595240 .

Background: Bisphenol A (BPA) is one of the most widely used synthetic chemicals worldwide. BPA as an endocrine disruptor affects the reproductive systems through estrogenic and antiandrogenic proprieties. Resveratrol (RES) as a natural polyphenol and potent antioxidant exhibits protective effects against reproductive toxicity by inhibiting of oxidative stress. 48 male rats were divided into eight groups (n=6), including CONTROL, OLIVE OIL (0.5 ml/ day), Carboxy methylcellulose (CMC) (1 ml of 10 g/l), RES (100mg/kg/day), low dose of BPA (25 mg/kg/day), high dose of BPA (50 mg/kg/day), low dose of BPA + RES, and high dose of BPA + RES. All treatments were done orally per day for 56 days. At the end of the 8th week, blood samples were collected for hormone assays. Then, the sperm parameters were analyzed, and the left testis was removed for stereological study.

Results: We showed a significant decrease in sperm parameters in the low and high doses of BPA groups compared to control groups (P<0.05). The volume of testicular components as well as the diameter and length of seminiferous tubules significantly reduced (11-64 %), and the total number of the testicular cell types decreased (34-67 %) on average in the low and high doses of BPA groups. Moreover, serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone hormones concentration showed a significant reduction in both doses of BPA groups (P<0.01). Nonetheless, treatment with RES could ameliorate all the above-mentioned changes in the low and high doses of BPA groups (P<0.05).

Conclusions: RES could prevent BPA-induced testicular structural changes and sperm quality via improving gonadotropin hormones and testosterone levels.

Background: Male fertility has gradually become a worldwide problem with limitations in the treatment. Alpha-lipoic acid, has been applied to improve the quality of sperm in clinical practice. However, there was currently no high quality of systematic review to evaluate the effects of alpha-lipoic acid on sperm parameters.

Material and methods: The Cochrane Library, MEDLINE, EMBASE, Web of Science, Clinicaltrials.org, China National Knowledge Infrastructure Database, China Biology Medicine Database, etc., were retrieved. Related randomized controlled trials had be collected and selected up to March 10, 2022. English literature and Chinese literature were searched using terms including "male infertility", "semen", "sperm", "alpha-lipoid acid", "α-lipoid acid", "alpha lipoid acid", "thioctic acid". All statistical analyses were conducted by RevMan 5.3.

Results: A total of 133 participants in three studies included. Compared with sham therapy, treated with alpha-lipoic acid has significant improvement in the following sperm parameters, including abnormal sperm forms (mean difference[MD] = -1.06, 95% confidence interval [CI] = -1.29-0.84, p < 0.00001), sperm concentration (MD = 3.98, 95%CI = 2.28-5.67, p < 0.00001), sperm total motility (grade a+b+c) (MD = 6.68, 95%CI = 4.88-8.48, p < 0.00001) and progressive motility(grade a+b) (MD = 6.90, 95%CI = 5.62-8.17, p < 0.00001) and semen volume(MD = -0.17, 95%CI = -0.31-0.02, p = 0.03).

Conclusions: In this meta-analysis of three randomized controlled trials, compared with other treatments, alpha-lipoic acid could improve normal sperm forms, sperm concentration, sperm total motility and progressive motility, but more stringent randomized controlled trials must be conducted.

Background: Because of limited differentiation to endothelium from mesenchymal stem cells, it has been strongly recommended to use endothelial progenitor cells for the regeneration of the damaged endothelium of corpora cavernosa. This study was performed to investigate the immortalized human cerebral endothelial cells and their capability for repairing erectile dysfunction in a rat model of cavernous nerve injury. Circulating endothelial progenitor cells were isolated from human fetal brain vasculature at the periventricular region of telencephalic tissues. Over 95% of CD 31-positive cells were sorted and cultured for 10 days. Human cerebral endothelial progenitor cells were injected into the cavernosa of rats with cavernous nerve injury. Erectile response was then assessed. In in vivo assays, rats were divided into three groups: group 1, sham operation: group 2, bilateral cavernous nerve injury: and group 3, treatment with human cerebral endothelial cells after cavernous nerve injury.

Results: Established immortalized circulating endothelial progenitor cells showed expression of human telomerase reverse transcriptase transcript by RT-PCR. They also showed the expression of vascular endothelial growth factor, von Willebrand factor, vascular endothelial growth factor receptor, and CD31, cell type-specific markers for endothelial cells by RT-PCR. In in vitro angiogenesis assays, they demonstrated tube formation that suggested morphological properties of endothelial progenitor cells. In in vivo assays, impaired erectile function of rat with cavernous nerve injury recovered at 2, 4, and 12 weeks after transplantation of human cerebral endothelial cells into the cavernosa.

Conclusions: Telomerase reverse transcriptase-circulating endothelial progenitor cells from fetal brain vasculature could repair erectile dysfunction of rats with cavernous nerve injury.

Background: At present, there is a lack of standardized preparation methods of sperm antigen for the detection of antisperm antibody (AsAb). To screen sperm antigen mimotopes from a phage display random peptide library and use them to establish an enzyme-linked immunosorbent assay (ELISA) for the detection of AsAb, immunoglobulins were extracted from the sera of rabbits with positive AsAb and negative AsAb, respectively, by the saturated ammonium sulfate method, and a phage display 12-mer peptide library was affinity panned by the extracted immunoglobins coated on the ELISA plate. Then, the obtained positive phage clones were identified by ELISA and sent for sequencing and peptides synthesis. Last, a diagnostic ELISA was established to detect clinical serum and seminal plasma samples.

Results: A total of sixty phage clones were chosen by affinity panning, and sixteen of them reacted positively with AsAb in indirect ELISA and sandwich ELISA. Following DNA sequencing and translation, the peptide sequences of the sixteen positive clones were obtained. By comparison in Blast database, four of sixteen positive clones were found to be closely related to male reproduction. Two (#1 and #25) of four mimotopes were synthesized, and an ELISA method was established using the two mimotopes as sperm specific antigens. One hundred and thirty-four serum samples and seventy-four seminal plasma samples from infertile couples were analyzed by the established ELISA with #1 and #25 mimotopes, respectively. The positive rates of AsAb in serum samples were 20.15% (27/134) for #1 and 11.19% (15/134) for #25, respectively, and the coincidence rate between them was 91.04% (122/134). The positive rates of AsAb in seminal plasma samples were 1.35% (1/74) for both #1 and #25, and the coincidence rate was 100%.

Conclusion: Sperm antigen mimotopes can be obtained successfully by the phage display technique, and can be used as standard sperm specific antigens to establish an ELISA method for the detection of AsAb.

Background: Sperm cryopreservation is an effective method of fertility preservation for disease-related and social sperm freezing. In total, 662 subjects (range: 15-65 years-of-age; mean: 33.49 ± 8.79 years-of-age) were included in this study to investigate the population characteristics, semen quality, and usage of autologous sperm preservation patients in Beijing. Of these, 351 were cancer patients (53.02%, 31.14 ± 7.32 years-of-age) and 311 were non-cancer patients (46.98%, 36.14 ± 9.54 years-of-age).

Results: We found that the number of preservation cases increased steadily from 2015 to 2019; 89.73% of these had a bachelor's degree or above; 54.83%, 41.54%, and 3.63% were single, married, and divorced, respectively. The cases of cancers and oligozoospermia accounted for 71.30% of all patients; therefore, most patients required fertility preservation due to disease. The cancer group had a significantly lower sperm concentration, rate of progressive sperm after the frozen-thawed test, total progressive motility sperm count after the frozen-thawed test, and recovery rate of progressive motile sperm (RRPM) than the non-cancer group (all P < 0.05). Sperm count-related parameters were significantly affected by testicular cancer, while sperm motility-related parameters and RRPM were significantly affected by leukemia. The utilization rate of preserved sperm was 6.34% after 6 to 78 months of follow-up. In terms of fresh or frozen embryo transfer, the clinical pregnancy rate was 56.76% or 50.00%, and the live birth rate was 24.32% or 21.43%, respectively.

Conclusion: The need for autologous sperm preservation was dominated by patients with diseases, followed by the need for social sperm freezing. Tumors had a major negative impact on semen quality, and the usage rates of stored semen were at lower level compared to the number of sperm cryopreservation. Medical staff and patients should pay attention to both cognition-action consistency and cost-effectiveness in fertility preservation.