Andrologia

Background: Methotrexate (MTX) is widely administered to manage various cancers. However, MTX induces spermatogenic defects. Objective: This study investigated the protective effects of betaine (BET) against MTX–induced testicular damage. Materials and Methods: Forty-eight male mice were randomly divided into six groups: control, BET (300 mg/kg), MTX (20 mg/kg), and MTX (20 mg/kg) + BET (100, 200, and 300 mg/kg) groups. Testosterone levels, histological changes, sperm quality, apoptosis, and oxidative stress biomarkers were assessed to evaluate the protective effects of BET. Results: MTX disrupted germinal epithelium, reduced sperm quality, and decreased serum testosterone levels, as well as induced apoptosis and oxidative stress in the testicular tissue. BET dose dependently restored the testosterone levels and catalase (CAT) and superoxide dismutase (SOD). Furthermore, BET reduced lipid peroxidation, as indicated by decreased malondialdehyde (MDA) levels. BET preserved normal spermatogenesis, improved sperm quality, and reduced histological changes by MTX. Moreover, BET reduced apoptosis by decreasing the Bcl-2 Associated X-protein (Bax)/B-cell lymphoma 2 (Bcl-2) ratio in the testicular tissue of the MTX-intoxicated mice. Conclusion: The results indicate that BET mitigates testicular harm triggered by MTX by inhibiting apoptosis and decreasing oxidative stress levels.

Purpose: This study aims to develop and validate predictive nomograms for prostate cancer (PCa) and clinically significant PCa (csPCa) in prostate-specific antigen (PSA) gray zone of 4−10 ng/mL, utilizing transrectal ultrasound five-grade scoring system (TRUS-5), prostate imaging reporting and data system (PI-RADS) score based on multiparametric magnetic resonance imaging (mpMRI) and clinical parameters. Method: A retrospective analysis was conducted on a cohort of 383 patients with elevated PSA levels in the gray zone who underwent initial TRUS-guided 12-core prostate biopsy between January 2018 and December 2020. Multivariate logistic regression analyses were utilized to identify independent predictors for PCa and csPCa and to establish predictive nomograms. The diagnostic performance, calibration ability, and clinical usefulness of each model were assessed through receiver operating characteristic (ROC) curve analysis, calibration curve analysis, and decision curve analysis (DCA), respectively. Results: Two diagnostic nomograms were developed based on five risk factors (age, free/total PSA [(f/t) PSA] ratio, prostate volume [PV], TRUS-5, and PI-RADS score) to predict PCa and five risk factors (PSA, (f/t) PSA, PV, TRUS-5, and PI-RADS score) for csPCa of PSA gray zone patients. The TRUS-5/PI-RADS combined model demonstrated higher area under the curves (AUCs) (0.865 for PCa and 0.910 for csPCa) compared to the models based on PI-RADS score or TRUS-5 (p <0.05), as well as the greater net benefits across a wide range of threshold probabilities for PSA gray zone patients. Conclusion: The current study presented valuable TRUS-5/PI-RADS combined nomograms for predicting PCa or csPCa in patients within the PSA gray zone, which may serve as useful tools for the clinical management of PCa and csPCa.

During the intracytoplasmic sperm injection (ICSI) procedure, 10% polyvinylpyrrolidone (PVP) is commonly used as a selection medium to decrease sperm motility. The study aimed to determine the effect of different concentrations of PVP (5% and 10%) on sperm apoptotic transcripts, sperm DNA fragmentation (SDF), embryo cytokinetic, and clinical characteristics in the ICSI program. In the study, 60 couples with male factor infertility underwent ICSI insemination using either 5% or 10% PVP concentration. Metaphase II (MII) oocytes were divided into two groups, with one group injected with sperm in 5% PVP and the other in 10% PVP. After fertilization, the zygotes were cultured using a time-lapse microscope to assess morphokinetic parameters also, simultaneously with the ICSI procedure, SDF and apoptotic transcript levels were quantified using reverse transcription quantitative polymerase chain reaction (qPCR). The study found that DNA fragmentation was lower in sperm from the 5% PVP group compared to the 10% PVP group. Additionally, the expression levels of B-cell lymphoma (BCL2) and the 70 kilodalton heat shock proteins (HSP70) genes were significantly higher in 5% PVP compared to 10% PVP, while the transcript levels of the Bcl-2-associated X protein (BAX) gene were lower in 5% PVP. The 5% PVP group also demonstrated higher fertilization and high-quality embryo formation rates. Cytokinetic variables were significantly different between the two groups, and the rates of fragmentation, uneven blastomere, reverse cleavage (RC), and embryo arrest were higher in the 10% PVP group. The study concluded that a low concentration of PVP (5%) is a suitable replacement for 10% PVP in ICSI cycles for male factor infertility.

Background: The rate of male infertility has increased in the last decades. One factor that may improve sperm quality and testosterone is fish consumption, which supplies the organism with essential nutrients. Aim: To determine evidence of a relationship between the frequency of fish consumption and sperm quality. Methods: Seventy-four healthy men, aged 25–45 years, were involved in this observational study. Semen quality was evaluated by spermogram analyses and testosterone was measured in blood. Volunteers were classified as low, moderate, and high fish consumption groups according to the replies indicated in a questionnaire they had to fill out. Results: The moderate fish consumption group showed better semen quality with all spermogram parameters in the reference range and the low fish consumption group manifested the worst semen quality with sperm morphology below the reference range. The low fish consumption group had lower testosterone levels (3.6 ± 0.9 vs. 4.3 ± 1.5; p=0.04), decreased nonprogressive spermatozoa (11.9 ± 6.2 vs. 15.8 ± 8.2; p=0.04), and lower semen volume (3.1 ± 2.0 vs. 3.6 ± 1.3; p=0.06) compared to the moderate fish consumption group. Positive associations were detected between the frequency of fish consumption, the semen volume, and nonprogressive spermatozoa, respectively. Conclusions: Fish consumption at moderate level such as once a week leads to improvement in sperm quality and testosterone levels.

Objective: To evaluate the efficacy and safety of low‑intensity pulsed ultrasound (LIPUS) for the treatment of Peyronie’s disease (PD). Methods: To analyze the treatment effect of 106 PD patients, 56 patients treated with LIPUS as therapy group and 50 patients with oral L-carnitine and vitamin E as control group. 56 patients were treated with LIPUS three times per week for four consecutive weeks (12 times totally). Penile erectile pain, erectile function, the size of penile plaques, and penile curvature were assessed for all of these 106 PD patients before treatment and at 4- and 24-week follow-ups to evaluate the treatment effect. Erectile pain was assessed by visual analog scale (VAS), while erectile function using the International Index of Erectile Function scale (IIEF-5), and penile plaque size was measured by ultrasound. After alprostadil was injected into the penile body to induce a full erection, the penis was measured with a protractor at the maximum bending degree. Results: After 4-weeks follow-up, the VAS scores of the LIPUS group were significantly lower than the baseline (P<0.01), while no significant differences were found in the control group (P>0.05). After 24-weeks follow-up, the VAS scores of the control group reduced significantly but also were significantly higher than the LIPUS group (P<0.01). The IIEF-5 scores of the LIPUS group were significantly higher than the baseline (P<0.01). While the IIEF-5 scores of the control group showed no significant differences both after 4- and 24-weeks follow-up (P>0.05). The penile plaque size showed no significant differences after 4- and 24-weeks follow-up both in the LIPUS group and the control group (P>0.05). The penile curvature degrees showed a significant reduction after 4-weeks follow-up in LIPUS group (P<0.01). While the penile curvature degrees of the control group showed no significant differences both after 4- and 24-weeks follow-up (P>0.05). No complications, such as penile pain, hematoma, or skin ecchymosis, were observed during the entire process of LIPUS treatment, nor did they appear during follow-up. Conclusions: In patients with acute PD, LIPUS could relieve erectile pain and improve erectile dysfunction. Moreover, it appears not to reduce plaque size and not to have a clinically significant effect on penile curvature. Furthermore, LIPUS also shows a good safety profile during the management of PD and should be recommended for the clinical management of PD.

Exposure to cadmium chloride (Cd) is linked to reproductive disorders. Curcumin (CUR), a traditional medicinal compound, has been considered for its therapeutic properties. The present study evaluated the antioxidant effects of CUR and liposomal CUR on Cd-induced testicular toxicity. Mice were exposed to Cd (2.5 mg/kg as a single intraperitoneal dose), Cd + CUR at 50, 100, and 200 mg/kg, and Cd + liposomal CUR (15 mg/kg) orally for 7 days. At the end of the treatment period, histological studies, sperm parameters, oxidative stress parameters, and blood–testis barrier (BTB) integrity were performed. Cd-induced histopathological deleterious changes in the testis and epididymis tissues increased BTB permeability. It caused a significant decrease in sperm count and viability (p<0.001), as well as an increase in sperm abnormality (p<0.001) and a reduction in the antioxidant activity of superoxide dismutase (SOD), glutathione (GSH) (p<0.001), and increased lipid peroxidation (LPO; p<0.001) compared to the control group. Co-treatment of CUR with Cd dose-dependently and significantly attenuated Cd’s destructive effects on sperm and oxidative stress parameters at 50 mg/kg (p<0.01) and 100, 200 mg/kg (p<0.001). Although the liposomal form of CUR showed protective effects against some Cd-induced changes, such as sperm viability and count (p<0.001), it did not significantly improve LPO and GSH levels. The results indicated that native CUR prevented Cd-induced reproductive toxicity in male mice by suppressing oxidative injury, and there was no superior effect of liposomal CUR over native CUR.

This study aims to evaluate the genomic effects of vitamin D (VitD) on steroidogenesis, sperm structure, and function in mice models with artificially induced vitamin D deficiency (VDD), while maintaining calcium and phosphorus homeostasis. qRT-PCR was utilized to measure the steady-state RNA levels of key steroidogenic genes, including CYP11A1, CYP19A1, 17βHSDH1, 3βHSDV1, and CYP24A1, involved in VitD metabolism, in testicular extracts from mouse models with varying degrees of VDD severity. Estradiol, testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) levels were also assessed. Furthermore, testicular histomorphometric analysis and evaluation of sperm structural and functional parameters were conducted. The study reveals a linear decrease in the expression of monitored steroidogenic genes with increasing severity of VDD. Moreover, in cases of mild and moderate VDD, testicular extracts exhibited significantly reduced levels of LH, estradiol, and testosterone. VDD has substantial effects on testicular steroidogenesis, which directly impacts spermatogenesis, independent of its established role in calcium regulation. Consequently, the reduction in steroidogenesis due to VDD contributes to the diminished efficiency of testicular spermatogenesis in individuals experiencing VDD, a prevalent condition worldwide.

Nonobstructive azoospermia (NOA) is considered to be the most severe form of male infertility. Meiotic arrest is one of the major causes of NOA and can be caused by single gene mutations. Here, a novel homozygous missense mutation (c.131G>T) in the MEI1 gene was identified through whole exome sequencing in a Chinese men with NOA caused by meiotic arrest. Bioinformatics and genetic analysis predicted that this novel mutation may be deleterious. Our findings confirm that spermatogenesis is arrested at the primary spermatocyte stage, with defective programed DNA double-strand breaks (DSBs) formation. In vitro functional analysis revealed that the defects of DSBs formation may be a result of a lower expression level of MEI1 protein in the mutant. Therefore, the NOA in this patient is likely caused by the single novel mutation in the MEI1 gene leading to meiotic arrest. Our report expands the mutation spectrum of MEI1 and provides new evidence that the MEI1 gene may serve as a diagnostic marker for genetic counseling in NOA patients.

Male infertility is frequently caused by decreased sperm motility. Sperm of low progressive motility showed abnormal energy metabolism and elevated autophagy rate, although the specific mechanisms remain elusive. Hypoxia-inducible factor 1α (HIF-1α) is a transcription factor activated by hypoxia and plays a crucial role in regulating biological oxygen homeostasis. Negative correlation between sperm motility and HIF-1α expression and a potential association with the PI3K/Akt/mTOR signaling pathway were observed. To further explore the mechanisms by which HIF-1α impacts sperm motility, normal human sperm were treated with cobalt chloride (CoCl2) or YC-1. Sperm autophagy rate, ATP production, levels of intracellular reactive oxygen species (ROS), mitochondrial membrane potential (MMP), and HIF-1α, p-AKT, p-mTOR, and LC3B were assessed. The results showed that CoCl2 or YC-1 decreased sperm motility and increased sperm autophagy rate. The levels of intracellular ROS, HIF-1α, p-AKT, p-mTOR, and LC3B were significantly increased, while the levels of sperm ATP and MMP reduced. These findings suggested that HIF-1α might affect mitochondrial structure and energy generation, leading to increased autophagy rate and decreased motility in human sperm, with the PI3K/Akt/mTOR pathway potentially playing a role in this process by exerting an inhibitory effect on autophagy.

Type 2 diabetes mellitus (T2DM) can trigger cell apoptosis of seminal vesicles (SVs) and impair seminal secretory functions. Complanatuside A (CA) is known for its anti-inflammatory and antioxidant effects, as well as its ability to repair cellular damage. This study aimed to explore the potential molecular mechanisms through which CA mitigates cell apoptosis in the SVs of type 2 diabetic mice. A streptozotocin-induced type 2 diabetic mice model was utilized, and a 1-month intervention using CA (70 mg/kg) was administered. We monitored body weight, blood glucose levels, SV volume, and concentration of SV fluid. Hematoxylin and eosin staining was used to assess tissue damage. RNA sequencing was applied to identify differential gene expression, and the expression of target genes (ARG2, PBK, SerpinB1a, E2F2) was verified by qRT-PCR. Changes in the apoptosis level of SV tissues in mice were detected with TUNEL staining. Compared to the control group, mice with T2DM exhibited decreased SV volume and SV fluid content, which was improved with CA treatment. Elevated expression of SerpinB1a and reduced apoptosis were observed in the T2DM-CA group compared to T2DM mice. In summary, CA can inhibit cell apoptosis in the SVs, there by improving tissue damage in type 2 diabetic mice. SerpinB1a may be involved in this process. This study provides a new theoretical foundation for the treatment of seminal vesicle secretory dysfunction in type 2 diabetes mellitus.

This study aims to investigate whether transfection of miR-486 in the corpus cavernosum of spontaneously hypertensive rats (SHR) can improve erectile function and its mechanism. SHR penile cavernous smooth muscle cells were divided into control group, mimic negative control transfection group, inhibitor negative control transfection group, miR-486 mimic transfection group, and miR-486 inhibitor transfection group. miR-486 mimic (50 nM), miR-486 inhibitor (100 nM), and corresponding negative control preparation were transfected into the corresponding groups of cells. The mRNA expressions of miR-486, TGF-β1, Collagen I, and Collagen III in each group were detected after transfection. Twelve 12-week-old healthy male SHR and 12 WKY rats were randomly divided into WKY control group, SHR control group, SHR + Agomir negative control (NC) group, and SHR + miR-486 Agomir group. In the SHR + miR-486 Agomir group, penile cavernosa was transfected with miR-486 agonist. Penile sponge internal pressure (ICPmax)/mean arterial pressure (MAP), the expression of miR-486, the ratio of smooth muscle to collagen (SM/C), and the expression of TGF-β1, Collagen I, and Collagen III in penile cavernosum tissues were determined. Compared with the control group, the expressions of TGF-β1, Collagen I, and Collagen Ⅲ in the miR-486 mimic transfection group of SHR rat corpus cavernosum smooth muscle cells were significantly decreased, while those in the miR-486 inhibitor transfection group were significantly increased (P <0.05). The ratios of ICPmax/MAP and SM/C in the SHR group were significantly lower than those in the WKY group and in the SHR + miR-486 Agomir group were significantly higher than those in the SHR group and the SHR + Agomir NC group (P <0.05). The expressions of TGF-β1, Collagen I, and Collagen Ⅲ in SHR group were significantly increased compared with those in WKY group, while those in SHR + miR-486 Agomir group were significantly lower than those in SHR group and SHR + Agomir NC group (P <0.05). The upregulation of the expression of miR-486 in the corpus cavernosum of SHR rats can inhibit fibrosis of the corpus cavernosum and improve erectile function.

Background. Although the use of anesthetics in prostate biopsy on pain has been well studied, its effect on the diagnosis of clinically significant prostate cancer (csCPa) is not well known. We aimed to investigate the contribution of performing the prostate fusion biopsy (PFB) procedure under general anesthesia (GA) to diagnosing csCPa. Materials and Methods. We retrospectively analyzed the data of 252 patients who underwent multiparametric magnetic resonance imaging (MpMRI)—guided PFB. Patients were divided into two groups: those under local anesthesia (LA) and GA. For LA and GA groups, csCPa capture rates in PFB were evaluated separately and in total for Prostate Imaging Reporting and Data System (PIRADS) 3, PIRADS 4, and PIRADS 5 lesions. It was investigated whether the PFB application under GA increases the chance of csCPa capture. Chi-square and z-ratio analysis was performed to determine the change in pathological diagnosis according to the anesthesia method. Results. A total of 411 lesions were detected by MpMRI in 252 men included in the study. LA was applied to 61.5% and GA to 38.5% of the patients. We found that the type of anesthesia affected the frequency of csCPa detection only for anterior lesions. Clinically insignificant prostate cancer (CIPC) was detected more frequently in the GA group than in the LA group. Considering PIRADS 3, PIRADS 4, and all lesion groups, benign pathology was statistically significantly more frequent in the LA group, while CIPC was statistically significantly more frequent in the GA group (p =0.000). Conclusion. Our study showed that performing PFB under GA may contribute to the diagnosis of csCPa in anterior region lesions. However, this effect could not be demonstrated when all lesions were examined. In fact, it causes more CIPCs to be caught. Considering that the CIPC approach is contradictory in the literature; multicenter, prospective studies with large participation are needed, taking into account patient and lesion characteristics.

Coridius chinensis is a traditional Chinese medicinal insect, whose extract (CcE) is widely used for male reproductive disorders. Manganese (Mn²⁺) as a heavy metal pollutant can cause toxicity to the reproductive system in mammals. Previous studies found that CcE can resist the apoptosis and oxidation by Mn²⁺ exposed to repair the damage of seminiferous epithelium in rat. However, the therapeutic effect of CcE in the testicular stroma remains unclear. Our study found that the slow mating behaviors of capture, riding, insertion, and ejaculation with Mn²⁺ exposure were improved by CcE treatment in male rat. The level of testosterone was significantly increased in CcE-treated groups. Meanwhile, the damage about less area and cell number in testicular stroma due to Mn²⁺ exposure was repaired after CcE treatment. Ultrastructure analysis of Leydig cells showed the larger mitochondria and more endoplasmic reticulum in Mn²⁺CcE groups became than that in Mn²⁺ group. Further experiments showed that mRNA and protein level of steroidogenic-related regulators (STAR, CYP11α1, and HSD3β1) were significantly decreased in Mn²⁺ group and strongly upregulated occurred at medium concentration of CcE given. Taken together, our results provide a new insight of CcE in promoting testosterone production of Leydig cells to protect male reproductive behavior from Mn²⁺ toxicity.

The purpose of this study was to investigate the effect of tocopherol supplementation and swimming in warm water on the spermatogenesis, expression of androgen receptors (ARs), and oxidative stress markers in mouse testis. Adult male mice were divided into seven groups: (A) control, (B) solvent, (C) vitamin E (VE), (D) swimming at 23°C water, (E) swimming at 23°C water and receiving VE, (F) swimming at 35°C water, and (G) swimming at 35°C water and receiving VE. Hormones were measured using ELISA. Spermatogenesis was examined through histopathology. The ARs were studied by immunohistochemistry. The testis oxidative stress markers were assessed using colorimetric assays. The distribution of VE in testis tissue was also evaluated using high-performance liquid chromatography (HPLC). Swimming of mice at 23°C was safe for sperm development. Swimming at 35°C resulted in lower testosterone, LH, sperm parameters, sperm differentiation, AR expression, SOD activity, and increased MDA in the testis, compared to control (P <0.05). The abovementioned parameters were significantly altered by VE, in comparison to the animals that swam in warm water at 35°C (P <0.05). The results of HPLC showed that tissue distribution of VE was significantly higher in group G, compared to group E (P <0.05). Swimming in water at 23°C is conducive to sperm development, whereas swimming at 35°C impairs sperm production. In conclusion, VE counteracts the negative effects of swimming at 35°C water on sperm development by altering the hypothalamic–pituitary–gonadal axis, distribution of VE, AR expression, and lipid peroxidation in testicular tissue.

Several studies have shown the association between decreased insulin sensitivity and the risk of male hypogonadism. Homeostatic model assessment of insulin resistance (HOMA-IR) is a well-established marker of decreased insulin sensitivity. The triglyceride–glucose index (TyG), calculated as ln fasting triglyceride mg/dL× fasting glucose mg/dL/2, was recently suggested to be a cheaper and a reliable surrogate marker to detect insulin resistance (IR). Our aim was to compare the performance of those two indexes in the prediction of male hypogonadism. The data on 192 men from infertile couples (18–50 years; sperm concentration <20 x 10⁶/mL) and 199 population-based matched controls collected during the years 2009–2012 (baseline) were evaluated retrospectively. Half of these subjects (72 subfertile men and 122 controls) were reinvestigated 5–10 years later (median year (range): 7 (5–10)). The patients receiving any hormonal therapy were excluded. Hypogonadism was defined as fasting, morning serum testosterone below 12 nmol/L. In receiver operating characteristic curve analysis, the optimal diagnostic cutoff values for baseline HOMA-IR and TyG to predict MetS at re-examination were 2.68 (Area Under Curve (AUC) = 0.886, p < 0.001) and 8.60 (AUC = 0.816, p <0.001), respectively. Moreover, in binary logistic regression analysis performed on the whole cohort using these thresholds for high values of HOMA-IR and high TyG, the odds-ratios (ORs) for hypogonadism were 6.48 (95% Confidence Interval (CI): 3.77–11.2; p <0.001) and 3.58 (95% CI: 2.17–5.94; p <0.001), respectively. Even though high HOMA-IR levels provided better risk estimates, high TyG was also highly related to the risk of hypogonadism. These markers can be utilized to identify men being at high risk of hypogonadism.

Objective. To study the reproductive hormones, semen quality, psychology, and sexual function of childbearing age men after recovery from Corona Virus Disease-2019 (COVID-19) infection. Materials and Methods. We recruited 387 men of childbearing age who recovered from COVID-19 infection and underwent prepregnancy health checks at the Reproductive Center of Shandong Maternal and Child Health Hospital from January to March 2023 as study subjects. Routine semen analysis and reproductive hormones were performed. The clinical symptoms, anxiety, depression, erectile function, and premature ejaculation questionnaire were investigated during the COVID-19 infection period. A control group of 226 men of childbearing age who were not infected with COVID-19 between August 2022 and October 2022 were selected based on questionnaire responses, reproductive hormones, and semen parameters. Results. The main clinical symptoms during COVID-19 infection of the 387 research subjects were fever (342/387, 88.37%), muscle pain (155/387, 40.05%), anosmia (124/387, 32.04%), cough (106/387, 27.39%), throat pain (53/387, 13.70%), nausea and vomiting (16/387, 4.13%), and testicular discomfort (5/387, 1.29%). The rates of anxiety and depression were 11.37% (44/387) and 32.82% (127/387), respectively; erectile dysfunction (ED) and premature ejaculation (PE) of the research subjects were accounted for 32.30% (125/387) and 6.98% (27/387). The IEF-5 score (P<0.001) decreased significantly compared to the control group, while the PHQ-9 score (P<0.001), the rate of increased ED (P<0.001), and the rate of depression increased (P<0.001). There were statistically significant differences in liquefaction time (P<0.05), the progressive sperm motility (P<0.05), total sperm motility (P<0.05), the rates of progressive sperm motility <32% (P<0.05), and total sperm motility <40% (P<0.05) between the 1 month, the 2 months after recovery from COVID-19 and controls. Circular cell counts (P<0.05) at 2 and 3 months were lower than in the controls. No changes in reproductive hormones before and after recovery from infection. Conclusion. COVID-19 infection exacerbates depression and ED. It has a sustained effect on sperm motility and liquefaction time in men. The effects of COVID-19 infection on semen persist for approximately 2 months, with recovery occurring in the third month. Reproductive hormone levels do not appear to be continuously affected after recovery from COVID-19.

Background. In this study, long-term functional, cosmetic, and quality-of-life outcomes of patients with congenital penile curvature who were operated on using the modified Essed–Schröder procedure were evaluated. Materials and Methods. Between 2009 and 2022, 233 patients with congenital penile curvature were operated using a modification of the Essed–Schröder technique. The average age of the cases was found to be 23.7 ± 4.6 (18–37). The mean postoperative follow-up period was 76.1 ± 16.8 (18–153) months. At the end of the follow-up period, 203 of 233 patients were interviewed retrospectively, and standard questionnaires were filled out to evaluate the functional, cosmetic, and quality-of-life results of the procedure. Results. There was a curvature ventral in 103, left lateral in 40, right lateral in 30, dorsal in 17, dorsolateral in 8, and ventrolateral in 5 cases. The mean degree of curvature was found to be 51.7 ± 9.4 (30–80). Recurrent curvature was detected in 16 cases (7.14%), and discomfort due to suture palpation was detected in 17 cases (8.37%). No case reporting erectile dysfunction was detected. 90.6% of the patients reported that they were satisfied with the operation. As a result, the curvature was effectively corrected, and the sensation of postoperative suture palpation was minimized. It has been determined that it increases patient and partner satisfaction and improves the quality of life. Conclusions. The modified Essed–Schröder technique is a relatively simple technique and provides successful functional and cosmetic results. It also provides a significant improvement in quality of life.

Background. Currently, there are few studies on the effects of hyperlipidemia on semen parameters and serum hormones in men. In this study, we divided the study subjects into two groups of normal and hyperlipidemia according to the criteria, and observed the differences between semen parameters and serum reproductive hormones in hyperlipidaemic men and normal men, to explore the potential associations between the indicators. Materials and Methods. Eight hundred eighty five men attending infertility clinics in six hospitals from September 2016 to June 2017 were selected. Their lipid levels, semen parameters, and serum reproductive hormone levels were tested, and a total of 480 men with normal lipids and 405 men with hyperlipidemia were selected according to the criteria, and the relationship between semen quality, serum reproductive hormones, lipids and semen parameters, and serum hormones was statistically analyzed. Results. There was no significant difference in semen parameters between hyperlipidaemic men and normal men (P >0.05), serum testosterone levels were significantly lower in hyperlipidaemic men (P <0.05), and there was a negative correlation between triglycerides (TG) and testosterone in the blood (P <0.05).Conclusion. Hyperlipidemia does not affect male semen parameters, and changes in testosterone in hyperlipidaemic men may be related to triglycerides.

Reproductive health is an important issue for humanity. In the context of the increasing incidence rate of male infertility, it is essential to find the factors that affect male reproductive health. Gastrointestinal health is closely related to reproductive health. Gastrointestinal hormones (GIH) and gut microbiota (GM), as important material foundations for gastrointestinal function, can promote or inhibit testicular reproductive function, including spermatogenesis, sperm maturation, androgen synthesis, and even broader male diseases such as sexual function, prostate cancer, etc. On the contrary, the functional health of the testes is also of great significance for the stability of gastrointestinal function. This review mainly discusses the important regulatory effects of GIH and GM on male reproductive function.

Primary ciliary dyskinesia (PCD) is a rare genetic condition characterized by destructive respiratory disease and laterality abnormalities due to randomized left–right body asymmetry. In men, PCD is also often associated with infertility due to immotile sperm owing to a malfunction of the sperm flagella. Pathogenic mutations have been found in more than 50 genes. Nonetheless, not all patients with PCD experience infertility. Therefore, to better understand the impact of PCD-associated mutations on male fertility, it is necessary to clarify the role of these genes in spermatogenesis. The CCDC103 p.His154Pro mutation has a high prevalence in PCD. Here, we present the identification and functional analysis of a biallelic mutation in CCDC103 identified in a familial case of PCD associated with male infertility. The biallelic CCDC103 mutations, NM_213607:c.161_162del(p.His55Serfs ∗9) and NM_213607:c.461A > C (p.His154Pro), were identified by whole-exome sequencing. Sanger sequencing validation was performed on all available family members, and the mutation was recessively separated with an infertility phenotype. The c.161_162del mutation breaks the reading frame of the protein and, therefore, is predicted to produce a nonfunctional protein. The tertiary structure of CCDC103-mutated protein indicated a significant conformational change that likely affected protein function. Transmission electron microscopy of spermatozoa showed that both the mid and principal regions of the flagellum lacked dynein arms, which was confirmed via immunofluorescence staining. Using the method of laser-assisted immotile sperm selection combined with intracytoplasmic sperm injection, the patient’s wife has a successful clinical pregnancy. These results extend the phenotype spectrum of the CCDC103 mutation in PCD.

This study aimed to investigate the potential benefits of frozen testicular sperm and to retrospectively analyze the clinical pregnancy and live birth outcomes following intracytoplasmic injection of fresh or frozen testicular sperm. A total of 468 infertile couples undergoing intracytoplasmic sperm injection cycles utilizing either fresh or frozen testicular sperm extracted between January 2017 and December 2021 were included in this analysis. Participants were categorized into two groups: those utilizing fresh testicular sperm (n = 324) and those utilizing frozen testicular sperm (n = 144). Outcome measures encompassed fertilization rate, embryo development, clinical outcomes, and birth status of infants. Statistical analysis revealed no significant differences in 2PN fertilization rate, Day 3 (D3) available embryo rate, high-quality embryo rate, blastocyst formation rate, clinical pregnancy rate, live birth rate, and preterm birth rate between the two groups. Although the preterm birth rate in the frozen testicular sperm group was lower compared to the fresh testicular sperm group, the difference was not statistically significant (5.6% vs. 15.1%). Notably, there were no discernible distinctions in clinical pregnancy and birth outcomes, as well as infant birth parameters, between the fresh and frozen testicular sperm groups. These findings suggest that frozen testicular sperm holds practical value and warrants consideration for clinical application.

To investigate the correlation between methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphism, homocysteine, and male infertility with varicocele in North China. One Hundred infertile males with varicocele (VC; grade II-III, VC group) and 100 healthy males with normal semen parameters and no varicocele (NC group) were recruited for PCR microarray, blood and semen testing. Compared with the CC genotype in the NC group, the TT genotype in the NC group and the CC genotype in the VC group showed no significant changes in sperm motility ( P = 0.191 ; P = 0.130 ), sperm density ( P = 0.591 , P = 0.643 ), plasma homocysteine level ( P = 0.511 ; P = 0.677 ), and seminal plasma MDA ( P = 0.752 ; P = 0.451 ). In contrast, VC patients with the TT genotype had higher plasma homocysteine level and seminal plasma MDA levels ( P < 0.001 ), lower partial pressure of oxygen in seminal pulse (PO2; P < 0.001 ) and poorer sperm quality ( P < 0.001 ), as compared with the CC genotype. This suggests that MTHFR C677C>T may not be a risk factor for male Varicocele in North China. However, this may affect the oxidative stress associated with homocysteine expression, which in turn affects semen parameters in VC patients. Larger studies are needed to validate our findings.

The purpose of this study was to evaluate the differences in sperm function and embryo morphokinetics following sperm cryopreservation by ultra-rapid freezing or rapid freezing methods compared to fresh spermatozoa. Thirty samples of normozoospermia were divided equally into fresh, ultra-rapid freezing, and rapid freezing groups. In the rapid freezing, sperm suspension was placed horizontally on nitrogen vapor. In the ultra-rapid freezing, sperm suspension with a straw-in-straw system was directly immersed in liquid nitrogen. Sperm function was assessed in terms of motility, morphology, viability, mitochondrial membrane potential, sperm DNA fragmentation, and acrosome reaction status. Also, the effects of two cryopreservation methods were assessed on global DNA methylation and DNA methyltransferase activity. Moreover, 730 embryos in three groups were cultured using time-lapse imaging until day 6 for embryo morphokinetics. Progressive motility (38.80 ± 4.21 vs. 34.86 ± 4.19; p <0.001) and viability (64.30 ± 6.24 vs. 58.10 ± 8.69; p<0.01) in ultra-rapid freezing were significantly higher than rapid group. DNA fragmentation and acrosome reaction were significantly increased in both cryopreserved groups (p <0.001). However, DNA fragmentation (16.30 ± 1.14 vs. 14.33 ± 2.94; p<0.01) was significantly higher in the rapid than the ultra-rapid freezing group. No significant differences were noted in global DNA methylation (p>0.05) and DNA methyltransferases activity (p>0.05) in fresh compared to cryopreservation groups. The kinetic times, including tPB2, tPNa, tPNf, t2, t3, t4, t5, t6, t7, t8, and tM, showed a significant delay in cell divisions in both cryopreservation groups. Furthermore, tPNa, tPNf, and t8 occurred with a significantly higher delay in embryos fertilized by sperm from the rapid freezing compared to the ultra-rapid freezing group. In addition, blastocysts formation was similar in both cryopreservation groups. Ultra-rapid freezing preserved the sperm biological integrity and lead to better embryo morphokinetics compared to the rapid freezing method. However, both methods of sperm cryopreservation were epigenetically safe.

Cold stimulation is the most common stressor in cold regions. Continuous cold stimulation can cause a series of pathophysiological changes in the body, such as aggregated neutrophils, macrophage activation, and increased inflammatory factors, which is also a risk factor for erectile function impairment. In addition, necroptosis is an important form of programmed cell death. However, the mechanisms of necroptosis in erectile function impairment due to cold stimulation have been very poorly studied. Therefore, we explored the mechanism of tumor necrosis factor-α (TNF-α)-mediated receptor interacting protein kinase 1 (RIP1)/receptor interacting protein kinase 3 (RIP3) necroptosis pathway on erectile function among cold-stressed rats. First, we established a cold-stressed rat model using cold stimulation and selected those rats that had developed erectile function impairment. Then, we used Necrostatin-1 (RIP1 specific inhibitor, Nec-1), Etanercept (TNF-α inhibitor, Ent), and Sildenafil (Sil) to intervene for 14 days and subsequently assessed their erectile function by apomorphine test and sexual behavioural test. Lastly, we performed various molecular studies and histopathological analyses of penile tissues collected from these rats after the experiments. We found that erectile function was impaired in cold-stressed rats, with increased penile tissue fibrosis and elevated levels of TNF-α and necroptosis. Contrastingly, intervention with Nec-1 and Ent restored erectile function, reduced penile tissue fibrosis, and decreased TNF-α and necroptosis levels, consistent with the results of intervention with Sil. Based on these results, we confirmed that the TNF-α-mediated RIP1/RIP3 necroptosis pathway was significantly altered in cold-stressed rats. In conclusion, inhibition of the TNF-α-mediated RIP1/RIP3 necroptosis pathway improved erectile function, suggesting that the specific downstream mechanisms need to be further explored.

Objective. The presence of infertility in couples not only results in heightened stress but also elevates the risk of developing psychological disorders, further exacerbating their situation. This study is designed to evaluate the relationship between semen analysis and depression, anxiety, and stress, as well as sexual function in infertile men. Method. This descriptive cross-sectional study was carried out at Amir Al-Momenin Hospital of Zabol between March 2019 and April 2020. The couples who were candidates for intracytoplasmic sperm injection according to male factors were recruited for the study. One hundered two men were asked to complete the depression, anxiety, and stress questionnaire (DASS-42) and the International Index of Erectile Function questionnaire (IIEF-15). The findings of the DASS and IIEF questionnaires were compared with the semen analysis test and reported. Results. The frequency of depression, anxiety, and moderate to very severe stress were found in 21 (20.6%), 40 (39.2%), and 23 (22.5%) cases, respectively. Surprisingly, 60 (59%) participants had erectile dysfunction. A significant correlation was found between mood disorders (depression, anxiety, and stress) and some components of the erectile function questionnaire, stress with erectile function ( p = 0.045 ), depression with overall satisfaction ( p = 0.011 ), and anxiety with intercourse satisfaction ( p = 0.048 ) and overall satisfaction ( p = 0.037 ). Also, there was a significant correlation between semen analysis parameters such as sperm motility with depression ( p = 0.035 ) and anxiety ( p = 0.037 ), normal sperm morphology with stress ( p = 0.034 ), progressive sperm motility with orgasmic function ( p = 0.006 ), and intercourse satisfaction ( p = 0.014 ). Conclusion. The higher the mental health, the higher the erectile function. Improvement of mood disorders leads to improvement of semen parameters and increases the chances of pregnancy. Psychological support may be helpful so, in addition to medical treatment, these people should also receive supportive psychological treatment.