Search Results (9)

Background: Undescended testis (UDT) is the most frequent pediatric anomaly of the male genitals, with a high incidence in premature male neonates. Due to the risk of long-term complications such as infertility, testicular malignancy, and psychological distress, special attention on the accuracy of management is needed. Despite the existence of well-established guidelines recommending early surgical intervention, significant delays in diagnosis, referral, and treatment are still observed in practice. Objectives: This study aims to evaluate the clinical management practices of undescended testis at a tertiary pediatric referral center over a ten-year period, with a particular focus on identifying risk factors associated with the development of postoperative testicular atrophy. Material and Methods: The following variables were extracted from patient records: the UDT location, age at surgery (we also recorded the mean age per year during the 10 years period), laterality (unilateral or bilateral), associated malformations and comorbidities, family history of UDT in first-degree relatives, type of surgical intervention (open vs. laparoscopic orchidopexy), and imaging diagnosis (ultrasonography, computer tomography). We considered testicular atrophy (TA) as negative outcome after orchidopexy. To identify the variables that independently contribute to the risk of postoperative testicular atrophy, we conducted a multivariate logistic regression analysis. Results: A total of 1082 pediatric patients UDT underwent orchidopexy between 2014 and 2023. The median age at surgery was 5.07 years, significantly exceeding current guideline recommendations. TA was observed in 24.8% of cases. Non-palpable testes, higher testicular position (particularly intra-abdominal), associated comorbidities, positive family history, and delayed surgical intervention were identified as independent risk factors for negative outcomes. The multivariate logistic regression model identified the most significant predictors of postoperative testicular atrophy as the presence of comorbidities (associated with more than an eightfold increase in risk), non-palpable testes (3.35 times higher risk compared to palpable ones), a positive family history of undescended testis (approximately 2.7 times higher risk), and older age at surgery, with each additional year of delay increasing the risk by 28.6%. Conclusions: Despite the availability of well-established guidelines, significant delays in the diagnosis and treatment of UDT persist in clinical practice. Testicular atrophy remains a relevant postoperative complication, particularly in patients with non-palpable testes, high testicular position, comorbidities, and late surgical intervention. Full article

Background: Puberty is a life milestone that marks the transition from childhood to adulthood. An ambispective Chongqing Pubertal Timing (CQPT) cohort was started in 2014 to understand pubertal timing and identify environmental risk factors. Methods: A total of 1429 children and adolescents were recruited and have been followed up once every 6 months for 8 years in a district of Chongqing, China. Data were collected via questionnaires for social and family environment, health conditions, gestational and maternal information, and in-person physical examinations by trained medical school graduate students in follow-ups. Environmental exposures of polycyclic aromatic hydrocarbons (PAHs), neonicotinoids, and heavy metals in urine samples were measured at different time points. Results: The mean ages at pubertal onset were 10.20 for thelarche, 11.62 for pubic hair development, and 11.84 for menarche in girls, and 11.16 for genital development, 11.66 for testicular enlargement, and 12.71 for first spermatorrhea in boys. Four OH-PAHs were associated with delayed timing of menarche, thelarche, pubic hair, and axillary hair development in girls, and thiacloprid was found to potentially impact genital stages in boys and axillary hair development in girls. Conclusions: We built a cohort to provide evidence of regional pubertal timing of boys and girls and the significant environmental factors. Further health outcomes, especially mental health and women’s health and its long-term health implications, will be followed. Full article

In older men, an age-related decline in testosterone is closely associated with various adverse health outcomes. With the progression of aging, hyperactivation of the local renin–angiotensin system (RAS) and oxidative stress increase in the testis. The regulation of RAS antioxidants may be a target to delay testicular aging and maintain testosterone levels. Exogenous nucleotides (NTs) have anti-aging potential in several systems, but there are no studies of their effects on the reproductive system. In our study, we examined the effects of exogenous NTs on testosterone synthesis and explored possible mechanisms of action. Therefore, senescence-accelerated mouse prone-8 (SAMP8) mice and senescence-accelerated mouse resistant 1 (SAMR1) were used in the experiment, and they were randomly divided into an NTs free group (NTs-F), a normal control group (control), a low-dose NTs group (NTs-L), a middle-dose NTs (NTs-M), a high-dose NTs group (NTs-H) and SAMR1 groups, and the testis of the mice were collected for testing after 9 months of intervention. The results showed that exogenous NTs could increase the testicular organ index in mice during aging, and delayed the age-associated decline in testosterone levels in SAMP8 male mice, possibly by modulating the local RAS antioxidant pathway and reducing oxidative stress to protect the testis. The present study provides new research clues for the development of preventive and therapeutic strategies for related diseases. Full article

Cisplatin is a commonly used chemotherapeutic agent with proven efficacy in treating various malignancies, including testicular, ovarian, cervical, breast, bladder, head and neck, and lung cancer. Cisplatin is also used to treat tumors in children, such as neuroblastoma, osteosarcoma, and hepatoblastoma. However, its clinical use is limited by severe side effects, including ototoxicity, nephrotoxicity, neurotoxicity, hepatotoxicity, gastrointestinal toxicity, and retinal toxicity. Cisplatin-induced ototoxicity manifests as irreversible, bilateral, high-frequency sensorineural hearing loss in 40–60% of adults and in up to 60% of children. Hearing loss can lead to social isolation, depression, and cognitive decline in adults, and speech and language developmental delays in children. Cisplatin causes hair cell death by forming DNA adducts, mitochondrial dysfunction, oxidative stress, and inflammation, culminating in programmed cell death by apoptosis, necroptosis, pyroptosis, or ferroptosis. Contemporary medical interventions for cisplatin ototoxicity are limited to prosthetic devices, such as hearing aids, but these have significant limitations because the cochlea remains damaged. Recently, the U.S. Food and Drug Administration (FDA) approved the first therapy, sodium thiosulfate, to prevent cisplatin-induced hearing loss in pediatric patients with localized, non-metastatic solid tumors. Other pharmacological treatments for cisplatin ototoxicity are in various stages of preclinical and clinical development. This narrative review aims to highlight the molecular mechanisms involved in cisplatin-induced ototoxicity, focusing on cochlear inflammation, and shed light on potential antioxidant and anti-inflammatory therapeutic interventions to prevent or mitigate the ototoxic effects of cisplatin. We conducted a comprehensive literature search (Google Scholar, PubMed) focusing on publications in the last five years. Full article

The trend to delay parenthood is increasing, impacting fertility and reproductive outcomes. Advanced paternal age (APA), defined as men’s age above 40 years at conception, has been linked with testicular impairment, abnormal semen parameters, and poor reproductive and birth outcomes. Recently, the significance of sperm microRNA for fertilization and embryonic development has emerged. This work aimed to investigate the effects of men’s age on semen parameters and sperm microRNA profiles. The ejaculates of 333 Portuguese men were collected between 2018 and 2022, analyzed according to WHO guidelines, and a density gradient sperm selection was performed. For microRNA expression analysis, 16 normozoospermic human sperm samples were selected and divided into four age groups: ≤30, 31–35, 36–40, and >40 years. microRNA target genes were retrieved from the miRDB and TargetScan databases and Gene Ontology analysis was performed using the DAVID tool. No significant correlation was found between male age and conventional semen parameters, except for volume. Fifteen differentially expressed microRNAs (DEMs) between groups were identified. Enrichment analysis suggested the involvement of DEMs in the sperm of men with advanced age in critical biological processes like embryonic development, morphogenesis, and male gonad development. Targets of DEMs were involved in signaling pathways previously associated with the ageing process, including cellular senescence, autophagy, insulin, and mTOR pathways. These results suggest that although conventional semen parameters were not affected by men’s age, alterations in microRNA regulation may occur and be responsible for poor fertility and reproductive outcomes associated with APA. Full article

Reproductive suppression is an adaptive strategy in animal reproduction. The mechanism of reproductive suppression has been studied in social animals, providing an essential basis for understanding the maintenance and development of population stability. However, little is known about it in solitary animals. The plateau zokor is a dominant, subterranean, solitary rodent in the Qinghai–Tibet Plateau. However, the mechanism of reproductive suppression in this animal is unknown. We perform morphological, hormonal, and transcriptomic assays on the testes of male plateau zokors in breeders, in non-breeders, and in the non-breeding season. We found that the testes of non-breeders are smaller in weight and have lower serum testosterone levels than those of breeders, and the mRNA expression levels of the anti-Müllerian hormone (AMH) and its transcription factors are significantly higher in non-breeder testes. Genes related to spermatogenesis are significantly downregulated in both meiotic and post-meiotic stages in non-breeders. Genes related to the meiotic cell cycle, spermatogenesis, flagellated sperm motility, fertilization, and sperm capacitation are significantly downregulated in non-breeders. Our data suggest that high levels of AMH may lead to low levels of testosterone, resulting in delayed testicular development, and physiological reproductive suppression in plateau zokor. This study enriches our understanding of reproductive suppression in solitary mammals and provides a basis for the optimization of managing this species. Full article

The evolutionary theory of aging supports a trade-off relationship between reproduction and aging. Aging of the male reproductive system primarily affects the testes, leading to a decrease in the levels of sexual hormones, alterations in sperm quality and production, and a decline in fertility that does not necessarily involve a complete cessation of spermatogenesis. Inflammation, oxidation, and apoptosis are events considered as predictors of pathogenesis and the development of age-related diseases that are frequently observed in aged testes. Although the molecular mechanisms are still poorly understood, accumulating evidence points toward pro-inflammatory molecules and reactive oxygen species as primary contributing factors for testicular aging. However, the real impact of aging-related testicular alterations on fertility, reproductive health, and life span is far from being fully revealed. This work discusses the current knowledge on the impact of aging in the testis, particularly of aging-related dysregulated inflammation and oxidative damage on the functioning of its different cell populations. More interestingly, this review covers the potential benefits of anti-aging interventions and therapies using either pharmacological compounds (such as non-selective non-steroidal anti-inflammatory medication) or more natural alternatives (such as various nutraceuticals or even probiotics) that exhibit anti-inflammatory, antioxidant, and anti-apoptotic properties. Some of these are currently being investigated or are already in clinical use to delay or prevent testicular aging. Full article

Androgen production, being important for male fertility, is mainly accomplished by the Leydig cells from the interstitial compartment of the testis. Testosterone plays a critical role in testis development, normal masculinization, and the maintenance of spermatogenesis. Within seminiferous tubules, appropriate Sertoli cell function is highly dependent on testicular androgen levels and is essential to initiate and maintain spermatogenesis. During aging, testosterone production by the testicular Leydig cells declines from the 30s in humans at a rate of 1% per year. This review outlines the recent findings regarding the use of flavonoids and isoflavonoids to improve testosterone production, contributing to normal spermatogenesis and preventing age-related degenerative diseases associated with testosterone deficiency. With the cumulation of information on the actions of different flavonoids and isoflavonoids on steroidogenesis in Leydig cells, we can now draw conclusions regarding the structure-activity relationship on androgen production. Indeed, flavonoids having a 5,7-dihydroxychromen-4-one backbone tend to increase the expression of the steroidogenic acute regulatory protein (StAR), being critical for the entry of cholesterol into the mitochondria, leading to increased testosterone production from testis Leydig cells. Therefore, flavonoids and isoflavonoids such as chrysin, apigenin, luteolin, quercetin, and daidzein may be effective in delaying the initiation of late-onset hypogonadism associated with aging in males. Full article

Data on growth and sexual maturation among boys from the rural Western Cape in South Africa is limited. A cross-sectional study of 269 school boys was conducted testing for serum luteinizing hormone (LH), follicle stimulating hormone (FSH), testosterone, sex hormone binding globulin (SHBG) and estradiol (E2); height, weight and body mass index (BMI); sexual maturity (using Tanner Stages) and a questionnaire (demographic and medical history). The median age at pubertal onset (Tanner Stage 2) and Tanner Stage 5 was 11.6 and 14.7 years, respectively. The median testicular volume was 5.5 mL at Tanner Stage 2 increasing from 2.5 mL at Tanner Stage 1 to 14.7 mL at Tanner Stage 5. Height and weight measurements were <25th & 50th percentile references at Tanner Stages 1–3. Controlling for confounders, serum FSH and LH increased (p < 0.05) from Tanner Stage 1 to 4 (by 4.1 and 3 mL respectively), and serum testosterone and estradiol increased after Tanner Stage 2 (by 12.7 nmol/L and 59.5 pmol/L respectively). These results indicate some delays in pubertal development of boys in the rural Western Cape when compared to boys from other settings possibly due to nutritional, socio-economic and environmental exposures. Changes in serum hormone levels were consistent with other populations. Initiatives to improve nutrition amongst Western Cape rural communities are recommended. Full article