Effects of clomiphene on the structure of the testis, epididymis and sex accessory glands of the rat

Young adult male rats were treated with clomiphene citrate, a non‐steroidal inhibitor of gonadotropin release in the rat. They were administered 2.5, 3.5, or 5.0 mg/100g/day for intervals up to 12 weeks. The weights of the sex accessory glands were less than those of control rats, and decreased with increasing dose and length of treatment. At the longer intervals, the weights of the testis and epididymis were also less than those of control animals. Microscopic alterations in the testis included a scarcity or even absence of late spermatids, the presence of necrotic cap‐phase spermatids, and accumulation of lipid droplets and large lysosome‐like structures in Sertoli cells. In rats treated for the longest interval, 12 weeks, testicular changes were even more extensive; degenerating primary spermatocytes were observed, and in one rat germ cells were virtually completely absent and the seminiferous tubules were occupied by Sertoli cells. The Leydig cells of treated animals were smaller than those of normal or control rats. Sperm were absent from the lumen of the caput epididymidis in most specimens. Although the epithelium of the caput appeared reduced in height in some samples, ultrastructural changes in cellular organelles were not detected. In most specimens of the cauda epididymidis, the lumen was small, irregularly shaped, and lacking in sperm. Light cells were prominent in the epithelium by virtue of their content of many apical vacuoles and dense granules. In some specimens of the distal cauda epididymidis, the duct had a circular profile and the lumen contained round cells and debris. The seminal vesicle and the ventral prostate were greatly suppressed. The normally tall columnar epithelia were reduced to a low columnar or cuboidal shape. Especially at the longer treatment intervals, the normally abundant rough endoplasmic reticulum was sparse, and in some samples secretory vacuoles were absent. The possible mechanism of production of these morphological changes is discussed, and the results are compared with those following treatment with other antifertility agents, including cyproterone acetate, a progestin, and a progestin‐androgen regimen.