E. Rovan

Effect of active immunization to luteinizing-hormone-releasing hormone on the fertility and histoarchitecture of the reproductive organs of male rat

SummaryThe feasibility of using a vaccine against luteinizing-hormone-releasing factor for supression of pituitary and gonadal functions has been indicated for some time. Antibody production against this low-molecular-weight, naturally occurring decapeptide, however, requires to be coupled to a carrier protein to enhance its immunogenicity. LHRH was coupled to diphtheria toxoid (DT). Adult male Sprague-Dawley rats with a mean basal body weight of 200g were immunized with anti-LHRH-DT (20 μg/injection/rat) at four-week intervals. An equal number of unexposed animals served as controls. Six animals were killed every two weeks up the end of the week 43. The vaccination schedule did not have any effect on the gain in body weight, nor was any adverse effect of vaccination observed in the course of the investigations. The pituitary, prostate, epididymis, testes, seminal vesicles, adrenal and thyroid were excised for determination of organ weight and histological examination. The adrenal, pituitary and thyroid showed no remarkable weight changes during the observation period, whereas the weights of the reproductive organs demonstrated significant reductions compared to those of the control group. The histopathology revealed marked to significant changes in the gonads and the accessory sex organs including the prostate. A progressive phase of regeneration of spermatogenesis was evident 98 days after vaccination. Total recovery of spermatogenesis was observed 300 days after vaccination. The mating studies showed the return of fertility 300 days after vaccination. The litters borne were normal. Prostate showed recovery after 154 days of vaccination. Our observations lend strong support to the hypothesis that anti-LHRH vaccine can be effectively used on the management of prostate carcinoma. If the vaccination is given together with a suitable dose of long-acting androgen, contained in an adequate delivery system, the regimen may be used for the regulation of male fertility.

Toxicity of Gossypol at Antifertility Dosages in Male Rats: Statistical Analysis of Lethal Rates and Body Weight Responses

Die Letalität und die Körpergewichtszunahme männlicher Wistarratten während der oralen Verabreichung von Gossypol‐Essigsäure (GAA) in Dosierungen zwischen 2.5 mg/kg und 30 mg/kg wurden statistisch ausgewertet. Eine verglichen mit den Placebo‐Gruppen signifikante Letalität nach 10wöchiger Behandlung mit niedrigen GAA‐Mengen (2.5, 5.0 und 7.5 mg/kg, p < 0.05) und mit hohen GAA‐Mengen (15, 20 und 30 mg/kg, p < 0.01) wurde festgestellt. Die bei Placebo‐Tieren innerhalb der Versuchsdauer festgestellte deutliche Körpergewichtszunahme blieb in allen mit GAA behandelten Gruppen aus. Die Wirkung hoher GAA‐Mengen, welche jeden zweiten Tag gegeben wurden, war mit den Auswirkungen nach täglicher Verabreichung identisch.

Effect of active immunization against luteinizing hormone-releasing hormone on the androgen-sensitive Dunning R3327-PAP and androgen-independent Dunning R3327-AT2.1 prostate cancer sublines.

The objective of this study was to determine the effect of active immunization against LHRH on the growth characteristics and histology of subcutaneously implanted tumors of the androgen‐sensitive Dunning R3327‐PAP and androgen‐independent R3327‐AT2.1 rat prostate adenocarcinoma sublines.

Antifertility Efficacy of Gossypol Acetic Acid in Male Rats

Die Wirkung der Gossypolessigsäure auf die Fertilität der männlichen Ratte

Androgens and the prostate

The prostate is androgen-dependent, requiring testosterone for its growth, development, differentiation and function. The involution of the prostate gland is initiated by testosterone depriviation (orchidectomy, medical castration). Subsequent administration of exogenous androgen and/or cessation of medical androgen blockade, however, results in re-growth of the prostate gland. However, it only attains its original size, and the response to androgen does not cause prostatic overgrowth.

Preparation of resin embedded unicellular organisms without the use of fixatives and dehydration media.

A method is presented for processing single cells for conventional ultrathin sectioning without the use of fixatives and dehydration media.

Effect of gossypol on bull spermatozoa in vitro

SummaryGossypol acetic acid in a concentration of 1,000 μg/ml solvent is able to immobilize 1 ml of native bull semen (sperm concentration: 8.5×108/ml; motility rate: 87.4%) within 30 min. After GAA treatment the spermatozoa show severe morphological damage on the membrane system, on the acrosomal complex and on the tubular complex of the end piece. The working mechanism of GAA can be assumed to be inactivation of enzyme activities or in direct reactions with plasma membrane material.

Ultrastructural analysis of rat testes after gossypol acetic acid (GAA) treatment.

SummaryThe present investigations were carried out to show the histological and ultrastructural alterations in rat testes 10 weeks after gossypol acetic acid treatment (dose: 30 mg gossypol acetic acid/kg/day). The morphological findings in the interstitial compartment were compared with the data from studies carried out to investigate the testosterone biosynthesis in gossypol acetic acid treated rats. No morphological changes in the epididymal and vasal epithelia were found; however, the germinal epithelial cells showed vacuolisation, pycnosis, disconnections of junctions, cytolysis and exfoliation of germ cells from the epithelium. The Sertoli cells were affected, too. Gossypol acetic acid seemed to stimulate the physiological activity pathologically; cellular organelles as mitochondria, endoplasmic reticulum, lysosomal vacuoles, pigment granules and nuclei were either enlarged in size and number or malformed in shape. The cellular contact was often restricted to spots or completely disconnected. If gossypol acetic acid was administered for a longer period of time some Sertoli cells were found to be unable to withstand the toxic stimulus, and the cells became necrotic too. In contrast to the toxic process in the germinal and Sertoli cells the Leydig cell compartment did not show any changes in fine structure, and therefore testosterone biosynthesis is presumed to be intact.

BCG-induced orchitis: structural changes during the degeneration of seminiferous tubules of rats and rabbits.

SummaryThe effect of BCG-induced orchitis on the structure of the seminiferous tubules in rats and rabbits was investigated by light and electron microscopy. The formation of cavities between Sertoli cells and the displacement of the cells of the spermatogenic cycle are the earliest changes to be observed. Individual Sertoli cells degenerate and separate from spermatocytes and spermatids. The latter form multinuclear complexes by a broadening of the intercellular bridges. The nuclei of spermatids undergo ring-like chromatin condensation in the rat and swelling in the rabbit. After the loss of spermatocytes and spermatids from the germinal epithelium, the remaining Sertoli cells have a very irregular shape and contain many residual bodies, which are probably derived from previously phagocytosed spermatids. They often contain crystalline inclusions. The nuclei of Sertoli cells show small chromatin condensations. In the rabbit, the tubular wall increases considerably in diameter. In the vicinity of a granuloma in the interstitium caused by BCG inflammatory cells accumulate around the wall of the seminiferous tubules. Although the basal lamina seems to be an obstacle, penetration of macrophages into the tubular lumen could be observed. However, this occurred only after the degeneration of the germinal epithelium.

The Endocrine Status of Gossypol — Treated Male Rats*

Der endocrine Status von Gossypol‐behandelten männlichen Ratten