The patient, assigned female at birth and aged 1 year and 7 months, presented with clinical manifestations of 46,XY disorders of sex development. The external genitalia exhibited a severely undermasculinized phenotype. Laboratory tests and gonadal biopsy indicated poor Leydig cell function and good Sertoli cell function. Genetic testing revealed compound heterozygous mutations of c.867-2A>C and c.547G>A (p.G183R) in the LHCGR gene. The patient was ultimately diagnosed with type II Leydig cell hypoplasia. Type II Leydig cell hypoplasia presents a broad spectrum of clinical phenotypes, characterized by a lack of parallel function between Leydig cells and Sertoli cells, and significant individual variability in spermatogenesis and gender assignment. This condition should be considered when there is poor Leydig cell function but good development of Wolffian duct derivatives.
Female ; Humans ; Infant ; Disorder of Sex Development, 46,XY/genetics* ; Leydig Cells/pathology* ; Mutation ; Receptors, LH/genetics* ; Testis/abnormalities*

OBJECTIVETo investigate the effects of hydro-alcoholic extract of Launaea acanthodes, a blood glucose lowering plant in folk medicine of Iran, on the structure of seminiferous tubules and serum gonadotropin and testosterone levels in hyperglycemic rats.

METHODSTwenty-four Wistar rats were randomly allocated into 4 groups (n=6): control, streptozotocin (STZ), STZ + insulin [STZ + Ins, 5 IU/(kg•day)], and STZ + Launaea acanthodes extract [STZ + Ext, 150 mg/(kg•day)]. Blood samples were collected at the 2nd and 4th weeks for detection of testosterone, follicle stimulating hormone (FSH) and luteinizing hormone (LH) with enzyme-linked immuno sorbent assay (ELISA), and the right testes of rats were removed at the 7th week for the evaluation of diameter and wall thickness of seminiferous tubules and number of Leydig cells using unbiased stereological techniques.

RESULTSIn comparison with the control group, at the 2nd week FSH (0.45 vs 0.03, 0.02, 0.02 IU/L in STZ, STZ + Ins and STZ + Ext groups, respectively) and LH (1.02 vs 0.37, 0.2, 0.29 IU/L) showed significant decreases (all P<0.05) and testosterone (4.2 vs 8.37, 7.78, 11.8 ng/mL) showed a remarkable increase (all P<0.05). The levels of these hormones became closer in the STZ + Ext and the STZ + Ins groups to the control at the 4th week. A significant decrease in diameter and wall thickness of seminiferous tubules and number of Leydig cells were observed in the STZ group as compared with the control (P<0.01).

CONCLUSIONSAdministration of Launaea extract demonstrated a beneficial impact on the protection of testis from pathogenic and degenerative effects of hyperglycemia which may be partly due to its potential antioxidative effects.

Animals ; Asteraceae ; chemistry ; Blood Glucose ; metabolism ; Cell Count ; Cholesterol ; blood ; Ethanol ; chemistry ; Gonadotropins ; blood ; Hyperglycemia ; blood ; drug therapy ; pathology ; Insulin ; blood ; Leydig Cells ; drug effects ; pathology ; Lipoproteins ; blood ; Male ; Plant Extracts ; pharmacology ; therapeutic use ; Rats, Wistar ; Seminiferous Tubules ; drug effects ; pathology ; Testosterone ; blood ; Triglycerides ; blood ; Water ; chemistry

OBJECTIVETo investigate the clinicopathological features of testicular malignant Leydig cell tumor (TMLCT) and improve the non-invasive diagnosis of the disease.

METHODSWe retrospectively analyzed the clinicopathological data on a case of TMLCT, detected the circulating tumor cells (CTC) in the peripheral venous blood, and reviewed the related literature.

RESULTSThe patient, a 47-year-old male, underwent radical orchidoepididymectomy under general anesthesia. Postoperative pathology confirmed the lesion to be TMLCT, which was mainly composed of Leydig cells and suspected with vessel carcinoma embolus. Immunohistochemistry showed the tumor cells to be positive for α-inhibin, Ki67, CD30, vimentin, EMA, and PLAP, but negative for CK, CK7, S100, CD10, SMA, Des, AFP, hCG, CEA, CK19, CD117, Oct-4, LCA, CD20, Pax-5, CD3, and CD43. Two CTCs were detected in the peripheral venous blood. The patient received 3 courses of chemotherapy for retroperitoneal multiple lymph nodes metastasis post-operatively. Subsequent CT imaging manifested no obvious reduction of the retroperitoneal lymph nodes and consequently the patient again underwent retroperitoneal lymphadenectomy and cryoablation. At 8 months after treatment, CT examination revealed notably enlarged retroperitoneal lymph nodes with the right adrenal gland evidently invaded.

CONCLUSIONTMLCT is an extremely rare sex-gonad stromal tumor with high malignancy and poor prognosis, and CTCs may be used for its early diagnosis and prognostic prediction.

Biomarkers, Tumor ; metabolism ; Humans ; Immunohistochemistry ; Leydig Cell Tumor ; drug therapy ; pathology ; surgery ; Lymph Node Excision ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplastic Cells, Circulating ; Prognosis ; Retrospective Studies ; Sex Cord-Gonadal Stromal Tumors ; drug therapy ; pathology ; surgery ; Testicular Neoplasms ; drug therapy ; pathology ; surgery

OBJECTIVETo study the effect of ethane dimethane sulfonate (EDS) injection on the volumes of different histological structures in the seminal vesicles of adult rats.

METHODSTwenty-seven male SD rats aged approximately 90 days were randomly divided into a control group (n = 14) and an EDS group (n = 13) to receive one intraperitoneal injection of normal saline and EDS (75 mg/kg bodyweight), respectively. At 7 and 12 days after treatment, the unilateral seminal vesicles were removed, methacrylate resin-embedded sections prepared and the total volumes of various structures in the seminal vesicles estimated using stereological methods.

RESULTSEDS treatment almost completely destroyed the Leydig cells in the testis, resulting in a drastic testosterone deficiency. The volume of the seminal vesicle (including the coagulating gland attached to the vesicle) was decreased by 53% in the 7 d EDS group (n = 6) in comparison with the 7 d control group (n = 7) ([138.2 +/- 12.9] vs [64.9 +/- 3.6] mm3, P < 0.01), but showed no significant difference between the 7 d and the 12 d EDS (n = 7) groups ([64.9 +/- 3.6] vs [55.4 +/- 7.7] mm3, P > 0.05). The total volumes of the glandular lumen, glandular epithelium, smooth muscular layer and adventitia were decreased by 96.7, 80.3, 57.6 and 67.0%, respectively, in the 12 d EDS group as compared with the 12 d control group (n = 7).

CONCLUSIONEDS induces drastic testosterone deficiency in adult rats, and significantly reduces the total volumes of the seminal vesicle lumen, glandular epithelium, smooth muscular layer and adventitia.

Animals ; Leydig Cells ; drug effects ; Male ; Mesylates ; pharmacology ; Organ Size ; drug effects ; Rats ; Rats, Sprague-Dawley ; Seminal Vesicles ; drug effects ; pathology ; Testis ; cytology ; drug effects ; pathology

OBJECTIVETo explore the relationship between physical and biological effects of alternating magnetic field and study the influence of the magnetic field on the reproductive function of murine testes.

METHODSThirty ICR mice were randomized into 5 groups: normal control, X-ray radiation, weak magnetic field (1000 Hz), 1 h strong magnetic field and 2 h strong magnetic field (2000 Hz). The mice were sacrificed at 7 days after the exposure for the analysis of testicular sperm motility, observation of histopathological changes in the testis by HE staining and evaluation of the changes by modified Johnsen grade criteria.

RESULTSThe rates of sperm motility were (42.37 +/- 10.24)% in the normal control group, (39.00 +/- 12.35)% in the X-ray radiation group, (36.00 +/- 17.28)% in the weak magnetic field group, (10.72 +/- 5.67)% in the 1 h strong magnetic field group and (4.44 +/- 2.87)% in the 2 h strong magnetic field group, respectively. Johnsen's scores decreased and the testis damage increased in a dose- and time-dependent manner.

CONCLUSIONMagnetic field, either strong or weak, may damage the testis function by inducing injury to seminiferous tubules and Leydig cells, thickening of the basal membrane, derangement, exfoliation, massive apoptosis and necrosis of spermatogenic cells in the lumen, situation of the epididymis, and consequently the absence of sperm.

Animals ; Electromagnetic Fields ; adverse effects ; Leydig Cells ; pathology ; Male ; Mice ; Mice, Inbred ICR ; Sperm Motility ; Testis ; cytology ; pathology ; radiation effects

OBJECTIVETo explore the effects of Di (2-ethylhexyl) phthalate (DEHP) on the testis and testicular gubernaculum of fetal KM mice in vivo and to investigate the mechanism of DEHP-induced cryptorchidism.

METHODSThirty healthy pregnant KM mice were randomly and equally divided into a blank control group, a corn oil control group and a DEHP group. The pregnant mice in the latter group were exposed to DEHP by gavage at the dose of 500 mg/kg body weight per day from gestation day 12 (GD12) through gestation day 19 (GD19). The effects of DEHP were observed on the number of fetuses per pregnancy, the ratio of male to female pups, the weight of the testis, the morphology and location of the testis and gubernaculum, the relative testis-bladder neck distance (TBD) and cranial suspensory ligament (CSL) residual. The expressions of the androgen receptor (AR), estrogen receptor (ER) and actin and proliferating cell nuclear antigen (PCNA) in the gubernaculum were detected by immunohistochemistry.

RESULTSDEHP reduced the testis weight and TBD, induced different degrees of testis maldescent, but produced no obvious effect on the body weight, the number of fetuses per pregnancy, the sex ratio and the testis gubernacular morphology. Under the light microscope, hypotrophy was seen in all the testis seminiferous tubules, spermatogenic cells and Sertoli cells, marked Leydig cell hyperplasia was noted, and the positive expression of AR in the gubernaculum was decreased in the DEHP group (P < 0.01).

CONCLUSIONDEHP could cause dysfunction of the testis gubernaculum via its anti-androgen effect, induce cryptorchidism, and cause dysplasia and dysfunction of Sertoli cells, Leydig cells and spermatogenic cells in fetal mice.

Animals ; Diethylhexyl Phthalate ; pharmacology ; Female ; Fetus ; drug effects ; Leydig Cells ; drug effects ; Male ; Mice ; Mice, Inbred Strains ; Pregnancy ; Sertoli Cells ; drug effects ; Testis ; cytology ; drug effects ; pathology

OBJECTIVETo observe the influence of the organophosphate insecticide dichlorvos on the apoptosis of Leydig cells in the male offspring of the SD rats exposed to dichlorvos, and to investigate the role of the changes of Leydig cells in genitourinary malformation.

METHODSTwenty-one pregnant SD rats were divided into a corn oil control group and 6 dichlorvos groups, the former given by gavage 1.0 ml corn oil daily, and the latter dichlorvos at the dose of 1, 4, 8, 16, 20 and 24 mg/kg daily from the 12th to 17th day of conception. After birth, 5 male neonates were randomly selected from each of the control and dichlorvos groups, and their testes were harvested to be analyzed by HE staining, immunohistochemistry with anti-caspase-3 antibodies and DAPI fluorescent staining. At 90 days after birth, another 5 of the male offspring were taken from each group and their testes were collected for the same analyses.

RESULTSStatistically significant differences were found in the number of both the caspase-3 positive and DAPI labeled Leydig cells in the testes of the rat offspring between the corn oil and the 4, 8, 16, 20 and 24 mg/kg dichlorvos groups (P < 0.05), but not between the control and the 1 mg/kg dichlorvos groups (P > 0.05). The apoptosis of Leydig cells was increased in the male offspring of the dichlorvos-exposed SD rats in a dose-dependent manner.

CONCLUSIONExposure of pregnant rats to dichlorvos can increase the apoptosis of Leydig cells in the male offspring, which, in turn, may reduce the number of Leydig cells, interfere with the testis function during the embryonic period, and damage the development of the genitourinary system.

Animals ; Animals, Newborn ; Apoptosis ; Dichlorvos ; toxicity ; Female ; Leydig Cells ; cytology ; drug effects ; Male ; Pregnancy ; Prenatal Exposure Delayed Effects ; pathology ; Rats ; Rats, Sprague-Dawley ; Testis ; cytology

OBJECTIVETo evaluate the role of spermatic nerves in the regulation of spermatogenesis.

METHODSFifty-four mature SD male rats (350-375 g) were randomized into a sham operation group (SO) and three experiment groups, and the latter underwent bilateral surgical removal of the superior spermatic nerve (SSN) or/and the inferior spermatic nerve (ISN). The animals were killed 1 month and 2 months after the operation. HE stain was used to observe spermatogenesis. Transmission electron microscopy and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) were employed to detect apoptosis.

RESULTSImpaired spermatogenesis was observed 2 months after the operation, with only Sertoli cells and a few spermatogonia remaining in the regressed tubules in all the treatment groups. The abnormal tubules in the SSN, ISN and SSN + ISN denervated testes accounted for (13.25 +/- 2.03)%, (11.0 +/- 4.36)% and (34.17 +/- 3.78)% respectively. Chromosome condensation and fragmentation in the germ cells were observed under the electron transmission microscope in all the denervated testes. TUNEL showed the spermatogonia and Leydig cells to be apoptotic in all the denervated testes and the incidence of the apoptotic cells in the SSN + ISN denervated testes was significantly higher than in the SSN or ISN denervated ones.

CONCLUSIONSpermatic nerves play an important role in spermatogenesis.

Animals ; Apoptosis ; Denervation ; Germ Cells ; pathology ; Leydig Cells ; pathology ; Male ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Spermatic Cord ; innervation ; Spermatogenesis ; physiology ; Spermatogonia ; pathology ; Testis ; innervation

OBJECTIVETo study the mechanism of dichlorvos leading to hypospadia of rats.

METHODSFrom the 12th to the 17th day of conception, 20 pregnant female rats (the experiment group) were given 10 mg/(kg x d) dichlorvos, while another 10 (the control group) administered 1.5 ml 0.9% NaCl/day. Out of 88 male newborns of the 20 experimental mother rats, 22 had hypospadia, while out of the 33 male newborns of the 10 controls, none had the problem. Five hypospadia newborns from the experiment group and another 5 normal ones from the control group were raised to sexual maturity, and then their testes were excised and embedded in paraffin, and the tissue sections were analyzed by regular HE staining and SP immunohistochemical staining with Calretinin.

RESULTSHE staining showed that the number of Leydig cells in the testis tissues of the hypospadia rats decreased significantly compared with the normal ones, but no change was observed either in the number or in the morphology of the seminiferous tubules. Moreover, the Calretinin positive Leydig cells were reduced dramatically in the testes of the hypospadia rats.

CONCLUSIONPregnant female rats, when exposed to dichlorvos, may cause reduction of testis Leydig cells in their male offsprings. Thus the probable mechanism of rat hypospadia induced by dichlorvos may lie in the decrease of the testosterone level caused by damage to Leydig cells from dichlorvos toxicity.

Animals ; Cell Count ; Dichlorvos ; toxicity ; Female ; Hypospadias ; chemically induced ; pathology ; Leydig Cells ; pathology ; Male ; Pregnancy ; Rats ; Rats, Sprague-Dawley ; Testis ; pathology

AIMTo quantitatively study the histological changes of the testis and epididymis as a result of a drastic reduction of testosterone secretion.

METHODSFourteen adult Sprague-Dawley rats were injected intraperitoneally with ethane dimethane sulfonate (EDS, 75 mg/kg) and the same number of animals were injected with normal saline as a control. At days 7 and 12 (after treatment), respectively, half of the animals from each group were killed. The testes and epididymides were removed and tissue blocks embedded in methacrylate resin. The cell number per testis was estimated using the stereological optical disector and some other parameters were obtained using other morphometric methods.

RESULTSThe EDS treatment resulted in an almost complete elimination of Leydig cells but had no effect on the numbers of Sertoli cells per testis. At day 7 after EDS treatment, many elongated spermatids were retained in the seminiferous epithelium and many round spermatids could be seen in the epididymal ducts. At day 12, a looser arrangement of spermatids and spermatocytes became evident, with apparent narrow empty spaces being formed between germ cells in an approximately radial direction towards the tubule lumen; the numbers (per testis) of non-type B spermatogonia and spermatocytes were similar to controls, whereas that of type B spermatogonia increased by 59%, and that of early round, elongating and late elongated spermatids decreased by 37%, 72% and 52%, respectively.

CONCLUSIONThe primary spermatogenic lesions following EDS administration were (i) spermiation failure and (ii) detachment of spermatids and spermatocytes associated with impairment in spermiogenesis and meiosis.

Animals ; Epididymis ; drug effects ; pathology ; Injections, Intraperitoneal ; Leydig Cells ; drug effects ; pathology ; Male ; Mesylates ; administration & dosage ; toxicity ; Rats ; Rats, Sprague-Dawley ; Seminiferous Tubules ; pathology ; Testis ; cytology ; drug effects ; growth & development ; pathology