Morphologic changes due to human chorionic gonadotropin in the rat testis: Role of vascular endothelial growth factor

Abstract

Introduction: Human chorionic gonadotropin (hCG) has an important role in the regulation of reproductive system and a high capacity to stimulate angiogenesis by secretion of vascular endothelial growth factor (VEGF). It could be also used for medical treatment of cryptorchidism, as it stimulates Leydig cells to produce testosterone, but its use has been discussed. Aim of the study was to evaluate the testicular morphological changes due to cyclic administration of hCG possibly related to VEGF effect. Methods: 80 pre-puberal male Sprague-Dawley rats were randomly divided in two groups hCG (50 U/I/ Kg) (n = 55/S) and placebo (n = 25/C) treated. The animals were sacrificed respectively after one (S1 n = 10; C1 n = 5), two (S2 n = 10; C2 n = 5) and three weeks of hCG or placebo treatment (S3 n = 35; C3 n = 15); a blood serum was obtained for evaluation of plasmatic testosterone. The testis, prostates, epididymides and seminal vesicles were drawn and weighted. Specimens were fixed in formalin and coloured by hematoxylin-eosin. Morphometric analysis of Leydig cell number, nuclear area and perimeter was carried out. Immunoistochemistry for VEGF has been performed with the avidin-biotin peroxidase technique. Statistical differences between groups, each of different age, were calculating using Student's T-test. Results: After the first week of hCG treatment it has been observed an increased testicular weight and volume (+/−6%) in experimental respect to control group. This result was not observed after the second and third week of treatment. Significant variations were also observed in the mean prostate weight, whereas mean seminal vesicles weight was significant in the S2 and S3 groups respect to control. In the hCG treated rats it has been observed a poor differentiation of the seminiferous epithelium, with high Leydig cell evidence and increased intertubular eosinophilic material. An interstitial edema was demonstrated without inflammatory cell changes. Morphometric analysis confirmed an increased number of Leydig cells that were always strongly immunostained for VEGF. Low-medium reactivity was present in spermatogonial, peritubular, endothelial and Sertoli cells. Testosterone plasmatic values showed a statistically significant and progressive increase. Conclusions: hCG treatment clutters the germinative line and modifies VEGF testicular expression, suggesting its role in male reproductive system. The increased number of Leydig cells and the immunostaining for VEGF suggests an intense interstitial and metabolic arrangement. The morphologic modifications induced by hCG treatment and its influence on testis function raise the question about its use in the medical treatment of cryptorchidism.

Effect of a single injection of gonadotropin-releasing hormone (GnRH) and human chorionic gonadotropin (hCG) on testicular blood flow measured by color doppler ultrasonography in male Shiba goats

“…B-mode ultrasonography is considered to be a more accurate, precise and reproducible method for measurement of TV in assessing testicular function and pubertal development [ 21 , 31 , 37 ]. An increase of TV recorded in this study after hCG injection was similar to those observed in men [ 14 ] as well as in rats [ 23 ].…”

Spermatogenesis and Cryptorchidism

“…In addition, there are reports which suggest that the hormonal stimulation in infancy may be damaging to the testes ( 39 ). It has been observed, in hCG-treated rats, a poor differentiation of the seminiferous epithelium, with high Leydig cell evidence and increased inter-tubular eosinophilic material ( 40 ). These experimental data emphasize the possible negative outcome of hormone therapy on germ cell line and its main action on Leydig cells.…”

“…The role of VEGF on spermatogenesis is unclear. Several findings have revealed several inhibitory effects of VEGF on spermatogenesis ( 40 , 41 ).…”

Effects of silencing epididymal vascular endothelial growth factor (VEGF) expression on hyaluronidase (HYD) activity in arsenic poisoning rats through downregulating VEGF receptor 2 (VEGFR2)

“…The combination of VEGF/VEGFR2 can inhibit apoptosis, promote endothelial cell proliferation, and improve vascular permeability [7][8][9]. Studies have also proved that VEGF and its receptor 2 were expressed in the epididymis, indicating that it may be may be involved in male reproduction [10][11][12].…”