Low testosterone (T) levels are a major cause of male infertility, as this hormone is crucial for several processes throughout the entire male reproductive tract. Leydig cells (LC) produce T through testicular steroidogenesis. Disrupted LC function can hinder steroid production and fertility. Among the factors that affect steroidogenesis, endocrine-disrupting chemicals (EDCs) raise concerns, as they disturb hormonal signaling. Chromium is classified as an EDC, and its main forms are hexavalent (Cr(VI)) and trivalent chromium (Cr(III)). While Cr(III) is controversially regarded as an essential metal, its compound Cr(III) picolinate (CrPic3) is used as a nutritional supplement due to its antidiabetic and antioxidant properties. This review aims to identify the possible effects of CrPic3 on testicular steroidogenesis and thus, on male fertility. The detriments caused by CrPic3 in LC include the inhibition of enzymes involved in steroidogenesis, and, as in other cells, the induction of mutagenesis and apoptosis. Remarkably, CrPic3 impacts male fertility through the alteration of reactive oxygen species (ROS), T levels, and sperm parameters (sperm motility and abnormal sperm count). However, gaps and inconsistencies exist in the literature concerning its effects on male fertility. Thus, further research is imperative to comprehend the underlying mechanisms of CrPic3 in the physiological processes relevant to male fertility, ensuring the supplement\'s safety for use by men.

Leydig cells are essential for steroidogenesis and spermatogenesis. An imbalance in the production of reactive oxygen species (ROS) and the cellular antioxidant level brings about oxidative stress. Oxidative stress (OS) results in the dysfunction of Leydig cells, thereby impairing steroidogenesis, spermatogenesis, and ultimately, male infertility. To prevent Leydig cells from oxidative insults, there needs to be a balance between the ROS production and the cellular protective capacity of antioxidants. Evidence indicates that medicinal plants could improve Leydig cell function at specific concentrations under basal or OS conditions. The increased usage of medicinal plants has been considered a possible alternative treatment for male infertility. This review aims to provide an overview of the impact of oxidative stress on Leydig cells as well as the effects of various medicinal plant extracts on TM3 Leydig cells. The medicinal plants of interest include Aspalathus linearis, Camellia sinensis, Moringa oleifera, Morinda officinale, Taraxacum officinale, Trichilia emetica, Terminalia sambesiaca, Peltophorum africanum, Ximenia caffra, Serenoa repens, Zingiber officinale, Eugenia jambolana, and a combination of dandelion and fermented rooibos (CRS-10). According to the findings obtained from studies conducted on the evaluated medicinal plants, it can, therefore, be concluded that the medicinal plants maintain the antioxidant profile of Leydig cells under basal conditions and have protective or restorative effects following exposure to oxidative stress. The available data suggest that the protective role exhibited by the evaluated plants may be attributed to their antioxidant content. Additionally, the use of the optimal dosage or concentration of the extracts in the management of oxidative stress is of the utmost importance, and the measurement of their oxidation reduction potential is recommended.

Sertoli-Leydig Cell Tumors (SLCT) are very rare neoplasms of the ovary (0.2%) and they belong to the group of sex cord-stromal tumors. Of these, 20% of the cases show heterologous elements. We report a case of a 22-year-old woman who presented with complaints of lower abdominal pain and secondary amenorrhea for 10 months. Physical examination revealed right lower abdominal tenderness and fullness. Imaging showed a right ovarian mass. She underwent right salpingo-oophorectomy with bilateral pelvic lymphadenectomy and omentectomy. Microscopic examination revealed a neoplasm with varied histomorphological patterns. The predominant pattern was an atypical proliferative mucinous tumor with foci of microinvasion. The other component was that of moderately differentiated Sertoli-Leydig Cell Tumor. Focal areas resembling carcinoid were also noted. Immunohistochemistry was performed and the Sertoli-Leydig Cells were positive for CD56, calretinin, inhibin, vimentin, and ER. The glandular component was positive for CK20, EMA, CEA, and CDX2. Synaptophysin and chromogranin were positive within nests resembling carcinoid. With the given histomorphological features and immunohistochemistry findings, a diagnosis of moderately differentiated Sertoli-Leydig Cell Tumor of the ovary with associated mucinous carcinoma and carcinoid was rendered. The presence of heterologous elements in SLCTs has been reported to be associated with poor prognosis.

The anticancer drug doxorubicin has been associated with several adverse side-effects including reproductive toxicity in both genders. The current review has complied the mechanisms of doxorubicin induced reproductive toxicity. The articles cited in the review were searched using Google Scholar, PubMed, Scopus, Science Direct. Doxorubicin treatment has been found to cause a decrease in testicular mass along with histopathological deformities, oligospermia and abnormalities in sperm morphology. Apart from severely affecting the normal physiological role of both Leydig cells and Sertoli cells, doxorubicin also causes chromosome abnormalities and affects DNA methylase enzyme. Testicular lipid metabolism has been found to be negatively affected by doxorubicin treatment resulting in altered profile of sphingolipids glycerophospholipids and neutral lipids. Dysregulation of 3β-hydroxysteroid dehydrogenase (3β-HSD) and 17β- hydroxysteroid dehydrogenase (17β-HSD) are strongly linked to testicular exposure to doxorubicin. Further, oxidative stress along with endoplasmic reticulum stress are also found to aggravate the male reproductive functioning in doxorubicin treated conditions. Several antioxidant enzymes such as superoxide dismutase, catalase, glutathione peroxidase (GPx) are downregulated by doxorubicin. It also disturbs the hormones of the hypothalamic-pituitary-gonadal (HPG)-axis including testosterone, luteinizing hormone, follicle stimulating hormone etc. In females, the drug disturbs folliculogenesis and oogenesis leading to failure of ovulation and uterine cycle. In rodent model the drug shortens pro-estrous and estrous phases. It was also found that doxorubicin causes mitochondrial dysfunction in oocytes with impaired calcium signaling along with ER stress. The goal of the present review is to comprehends various pathways due to which doxorubicin treatment promotes toxicity in male and female reproductive system.

This study summarizes the knowledge about effects of bisphenol A (BPA) and its analogues on reproduction of pigs and some parameters of their offspring during period 2011-2020. Bisphenols are known as one of the most harmful environmental toxicants with endocrine-disrupting properties. One study in the reference period related to male reproductive system. Treatment with an antagonist of G-protein coupled estrogen receptor (GPER) - G15, and bisphenol A and its analogues, tetrabromobisphenol A (TBBPA) and tetrachromobisphenol A (TCBPA) diversely disrupted protein molecules controlling the biogenesis and function of microRNA in Leydig cells. Nine studies examined the effect of BPA, bisphenol S (BPS) or fluorene-9-bisphenol (BHPF) on female reproductive system. From the possible protective effect\'s point of view seems to be perspective the administration of melatonin in BPA-exposed oocytes. Finally, two studies were found to evaluate the maternal exposure to BPA on offspring\'s meat quality, muscle metabolism and oxidative stress. Administration of methyl donor improved antioxidant enzymes activity and reduced oxidative stress in piglets.

Ochratoxin A is best known as a potent renal carcinogen in male rats and mice after necessarily protracted ingestion, although valid extrapolation to any human disease has not been verified. The hypothesis that the toxin is a cause of human testicular cancer was proposed a decade ago and has proliferated since, partly through incomplete study of the scientific literature. Archived tumorous rat testes were available from Fischer F344 rats exposed to continuous dietary exposure for half of or the whole life in London in the 2000s. Renal cancer occurred in some of these cases and testicular tumours were observed frequently, as expected, in both treated and untreated animals. Application of clinical immunohistochemistry has for the first time consistently diagnosed the testicular hypertrophy in toxin-treated rats as Leydig cell tumours. Comparison is made with similar analysis of tumorous testes from control (untreated) rats from U.S. National Toxicology Program studies, both of ochratoxin A (1989) and the more recent one on Ginkgo biloba. All have been found to have identical pathology as being of sex cord-stromal origin. Such are rare in humans, most being of germinal cell origin. The absence of experimental evidence of any specific rat testicular cellular pathology attributable to long-term dietary ochratoxin A exposure discredits any experimental animal evidence of testicular tumorigenicity. Thus, no epidemiological connection between ochratoxin A and the incidence of human testicular cancer can be justified scientifically.

Melatonin is a ubiquitous molecule and exhibits different effects in long-day and short-day breeding animals. Testosterone, the main resource of androgens in the testis, is produced by Leydig cells but regulated mainly by cytokine secreted by Sertoli cells. Melatonin acts as a local modulator of the endocrine activity in Leydig cells. In Sertoli cells, melatonin influences cellular proliferation and energy metabolism and, consequently, can regulate steroidogenesis. These suggest melatonin as a key player in the regulation of steroidogenesis. However, the melatonin-induced regulation of steroid hormones may differ among species, and the literature data indicate that melatonin has important effects on steroidogenesis and male reproduction.

Androgen insensitivity syndrome (AIS) is a very uncommon genetic disorder that results from the resistance of androgen receptor (AR) to androgen, which influences the formation of the male genitalia and in turn presents with female phenotype. Surgical resection of undesceaded testicle and different kinds of genitoplasty are crucial methods to correct the deformity of reproductive system, as well as hormone replacement therapy, which is an essential therapy for postoperational rehabilitation in AIS patients. A 43-year-old patient, who was socially female, was first admitted to gastroenterology department due to recurrent ascites and occasional abdominal pain with unknown origin. Taking physical examination, ultrasonography, karyotype analysis and sex hormone levels into consideration, the overall manifestations revealed the typical clinical features of complete androgen insensitivity syndrome. After that she was transferred to urology department for laparoscopic gonadectomy. During the surgery, doctors found that there was a vesical fistula on the upper wall near the conjunction between the bladder and ligamenta umbilicale medium, which explained the recurrent ascites for more than 4 years. After resecting the testicles and the tissues around the vesical fistula for histopathology, the result suggested Sertoli cell adenoma, hyperplastic Leydig cells and urothelium atypical hyperplasia. Hormone replacement therapy was given right after discharge. The hormone levels of follicle-stimulating hormone, luteinizing hormone, estradiol and progesterone were modulated by the dysfunction of androgen production after gonadectomy and hormone replacement therapy together with psychotherapy could stabilize her hormone levels and improve the quality of her life. The patient was suspicious of AIS family history and the pedigree was made to analyze her family which was possibly X-linked recessive pattern. We propose three possible hypotheses of the fistula, which are direct surgical injury, recurrence of bladder cancer and congenital urachal anomalies. But whether it is relevant between urachal anomalies and AIS is yet to be discovered.

BACKGROUND: Leydig cell hyperplasia (LCH) and Leydig cell tumours (LCTs) in children are rare, typically presenting with precocious puberty. Previously, orchidectomy was the routine management; however, more recently, testis-sparing surgery has been performed with good results. We present a series of unusual presentations of LCH, raising new management questions, and a review of the literature regarding LCH and LCT in children.
METHODS: We performed a literature search using Ovid Medline, PubMed, and Google Scholar, producing 456 articles. We reviewed all case reports and series containing paediatric patients, and relevant review articles.
RESULTS: We report three cases of LCH, two of which were incidental findings. All three cases underwent testis-sparing surgery. In the literature there were seven cases of LCH and 101 cases of LCT in prepubertal children. The most common presentation was with precocious puberty. Three cases of LCH and more than two-thirds of LCTs were managed with orchidectomy and overall only 11% of the cases underwent testes-sparing surgery (24% did not specify operative management). There were no reports of recurrence or malignancy.
CONCLUSIONS: Our case series presents three new clinical presentations of LCH that have not previously been reported in the literature: one of incomplete precocious puberty and two with incidental findings on ultrasound in asymptomatic children. Historically, children with the classic presentation of precocious puberty and a testicular lesion have been managed with orchidectomy. Nowadays, many clinicians advocate testes-sparing surgery given there have been no cases of malignancy. In children with no clinical or biochemical signs of precocious puberty, lesions identified on ultrasound can be safely monitored for a period of time. However, if the lesion does not regress, excisional biopsy is recommended to establish the diagnosis, ideally before the onset of puberty.
CONCLUSIONS: Leydig cell hyperplasia and tumours in pre-pubertal children are benign. Testes-sparing surgery with regular follow-up appears to be safe management.

This paper reviews the distribution of interstitial cells of Cajal (ICC) in the human gastro-intestinal (GI) tract, based on ultrastructural and immunohistochemical evidence. The distribution and morphology of ICC at each level of the normal GI tracts is addressed from the perspective of their functional significance. Alterations of ICC reported in as well as in GI stromal tumours are reviewed, with emphasis on the place of ICC in the pathophysiology of disease.