Apoptosis and cell proliferation in the seminal vesicles and coagulating glands of male Syrian hamsters exposed to diethylstilboestrol (DES).

Abstract

Regression of the accessory sex glands was induced in male Syrian hamsters by chronic exposure to diethylstilboestrol (DES), an agonist of 17beta-oestradiol. Experimental groups (n = 4-5) were killed at increasing time intervals up to 6 months after initiation of treatment. Organ atrophy was evaluated by morphological examination. Apoptosis in the seminal vesicles and coagulating glands was visualized by in situ analysis of DNA fragmentation. Cell proliferation was monitored by immunostaining nuclei of S-phase cells after pulse labelling with BrdU. The volume of the seminal vesicles decreased drastically after 2 weeks of DES administration due to a marked reduction of secretions in the lumen of the glands. Cell proliferation in the seminal vesicles was stimulated by chronic administration of DES. Mitotic activity mostly increased during the first month of treatment, leading to epithelial hyperplasia associated with progressive hyperplasia of the fibromuscular stroma. Evidence of epithelial dysplasia and metaplasia, often associated with an infiltration of polymorphonuclear leukocytes, was observed in animals exposed to DES for 4 months or more. Regression of the seminal vesicles was also associated with apoptosis in the gland epithelium. Apoptosis appeared 3 days after starting DES administration and culminated at 1 month. Thereafter the number of apoptotic cells decreased progressively, but apoptosis remained present until the end of treatment. In contrast, coagulating glands were less sensitive to DES. No major morphological changes were observed in these glands except for a moderate reduction of protein secretion. The levels of the apoptotic and proliferating cells indices were very low in the coagulating glands during DES treatment. In conclusion, these data point to different sensitivities of the accessory sex glands to DES exposure because DES induces extensive alterations of the normal morphology of the seminal vesicles, but shows only a moderate impact on the coagulating glands.