Cryptorchidism

Male reproductive health has declined as indicated by increasing rates of cryptorchidism, i.e., undescended testis, poor semen quality, low serum testosterone level, and testicular cancer. Exposure to endocrine disrupting chemicals (EDCs) has been proposed to have a role in this finding. In utero exposure to antiandrogenic EDCs, particularly at a sensitive period of fetal testicular development, the so-called 'masculinization programming window (MPW)', can disturb testicular development and function. Low androgen effect during the MPW can cause both short- and long-term reproductive disorders. A concurrent exposure to EDCs may also affect testicular function or damage testicular cells. Evidence from animal studies supports the role of endocrine disrupting chemicals in development of male reproductive disorders. However, evidence from epidemiological studies is relatively mixed. In this article, we review the current literature that evaluated relationship between prenatal EDC exposures and anogenital distance, cryptorchidism, and congenital penile abnormality called hypospadias. We review also studies on the association between early life and postnatal EDC exposure and semen quality, hypothalamic-pituitary-gonadal axis hormone levels and testicular cancer.

The incidence of testicular cancer is steadily increasing over the past several decades in different developed countries. If on one side better diagnosis and treatment have shone a light on this disease, on the other side, differently from other malignant diseases, few risk factors have been identified. The reasons for the increase in testicular cancer are however unknown while risk factors are still poorly understood. Several studies have suggested that exposure to various factors in adolescence as well as in adulthood could be linked to the development of testicular cancer. Nevertheless, the role of environment, infections, and occupational exposure are undoubtedly associated with an increase or a decrease in this risk. The aim of this narrative review is to summarize the most recent evidence regarding the risk factors associated with testicular cancer, starting from the most commonly evaluated (cryptorchidism, family history, infections) to the newer identified and hypothesized risk factors.

Congenital cryptorchidism, also known as undescended testis, is the condition where one or both testes are not in place in the scrotum at birth and is one of the most common birth defects in boys. Temporal trends and geographic variation in the prevalence of cryptorchidism from 1% to 9% have been reported in prospective cohort studies. The testes develop in the abdominal cavity and descend to the scrotum in two phases, which should be completed by gestational week 35. Thus, the risk of cryptorchidism is higher in preterm boys. In many cases a spontaneous descent occurs during the first months of life during the surge of gonadotropins and testosterone. If not, the testis is usually brought down to the scrotum, typically by surgery, to increase future fertility chances and facilitate cancer surveillance. The increasing frequency of impaired semen quality and testicular cancer, with which cryptorchidism is associated, represents a concern for male reproductive health in general and a need to understand its risk factors. The risk of cryptorchidism is closely related to gestational factors (preterm birth, low birth weight and intrauterine growth restriction), and especially maternal smoking seems to be a risk factor. Evidence is accumulating that the increasing prevalence of cryptorchidism is also related to prenatal exposure to environmental chemicals, including endocrine disrupting compounds. This association has been corroborated in rodents and supported by ecological studies. Conducting human studies to assess the effect of endocrine disrupting chemicals and their interactions is, however, challenged by the widespread concomitant exposure of all humans to a wide range of chemicals, the combined effect of which and their interactions are highly complex.

BackgroundCryptorchidism is one of the most common congenital disorders of the pediatric urogenital system. In addition to regulating the passage of substances into and out of the seminiferous epithelium, the blood-testis barrier (BTB) plays a critical role in maintaining a stable microenvironment for spermatogenesis. BTB alterations in cryptorchidism remain poorly characterized. This study aimed to establish a surgical unilateral cryptorchidism model in rats (SUCMR) and to investigate the injury and recovery patterns of both the BTB and spermatogenic function within this model.MethodsThe SUCMR was performed on 6-week-old male Sprague-Dawley rats, and testicular changes were observed after maintaining the modeling state for multiple time points. Simultaneously, another batch of rats underwent testicular descent surgery after maintaining the modeling for different durations to observe testicular recovery. The testis mass and volume, epididymal mass, epididymal sperm count and sperm malformation rate were quantified. After HE staining of testicular tissue, the seminiferous tubule structure was observed, and the seminiferous tubule diameter and seminiferous epithelium thickness were statistically analyzed. Biotin tracing experiments and transmission electron microscopy were performed to detect the BTB integrity. The expression of key BTB proteins ZO-1, OCCLUDIN, and CLAUDIN-11 was detected by WB. According to the normality of data distribution, a paired t-test or the Wilcoxon signed-rank test, an unpaired t-test or the Mann-Whitney U test, a one-way analysis of variance (ANOVA) or the Kruskal-Wallis test were used. A p-value of less than 0.05 was considered statistically significant.ResultsIn SUCMR, sloughing of the seminiferous epithelium was observed, resulting in testicular atrophy and spermatogenic abnormalities. The SUCMR impaired the integrity of the BTB and leaded to a progressive decrease in the expression of the key barrier proteins. Testicular atrophy and spermatogenic function injury induced by short-term SUCMR were reversible. But the disruption to the BTB was irreversible when the SUCMR was maintained for 4 weeks or longer.ConclusionIn this model, spermatogenic dysfunction and BTB injury progressed with increasing duration of abdominal retention, and abnormalities induced by 4 or 6 weeks of SUCMR did not recover within the post-orchiopexy observation period.