Estradiol treatment induces testicular oxidative stress and germ cell apoptosis in rats

• Published in: Apoptosis (London) Vol. 11; no. 8; pp. 1427 - 1437
• Main Authors: Chaki, S P, Misro, M M, Gautam, Dinesh K, Kaushik, Mahesh, Ghosh, D, Chainy, G B
• Format: Journal Article
• Language: English
• Published: Netherlands Springer Nature B.V 01.08.2006
• Subjects: Animals; Apoptosis; Apoptosis - drug effects; bcl-2-Associated X Protein - metabolism; Caspase 8 - metabolism; Catalase - metabolism; Cell Nucleus - drug effects; Cell Nucleus - metabolism; Cytoplasm - drug effects; Enzymatic activity; Estradiol - analogs & derivatives; Estradiol - pharmacology; Flow Cytometry; Follicle Stimulating Hormone - blood; Immunohistochemistry; In Situ Nick-End Labeling; Lipid Peroxidation - drug effects; Luteinizing Hormone - blood; Male; Oxidative stress; Oxidative Stress - drug effects; Pathogenesis; Peroxidation; Rats; Rats, Sprague-Dawley; Rodents; Spermatids - drug effects; Spermatozoa - drug effects; Superoxide Dismutase - metabolism; Testis - cytology; Testis - drug effects; Testosterone - metabolism
• ISSN: 1360-8185; 1573-675X
• DOI: 10.1007/s10495-006-8761-4

In order to understand the pathogenesis of estradiol induced effects in the seminiferous epithelium, studies were undertaken in adult rats with estradiol-3-benzoate administered for different durations. After 30 d of treatment, a significant rise in lipid peroxidation with concomitant fall in the activities of superoxide dismutase and catalase was observed. Both, serum and intra-testicular testosterone levels were found severely depleted. Seminiferous epithelium was devoid of elongated spermatids and spermatozoa by 30 d of treatment. Number of spermatocytes and round spermatids were significantly (p < 0.001) reduced. Flowcytometric analysis confirmed a drastic reduction of the haploid cell population (1c peak). Beginning from day 10 of treatment, there was a consistent rise in the number of pyknotic/apoptotic germ cells in the seminiferous epithelium. A gradual increase in Bax protein expression was observed with the duration of treatment. The shift in Bax immunostaining from the cytoplasm and nucleus of germ cells (at 10 d of treatment) to only nuclei of cells by 30 d of treatment was also noticed. By this time testicular tissue showed three-fold increase in caspase-8 enzyme activity. Viable testicular cells isolated in vitro decreased drastically subsequent to different periods of estradiol treatment. The above findings substantiate the fact that the testicular pathogenesis of estradiol benzoate treatment may be primarily because of altered reproductive hormone levels and high oxidative stress leading to germ cell apoptosis and subsequent germ cell loss in the seminiferous epithelium.