The influence of progestin and androgen on the fine structure of the male reproductive tract of the rat. I. General effects and observations on the testis

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Abstract
The combination of a progestin and androgen has received attention as a possible male contraceptive. The progestin is thought to reduce gonadotropin release and suppress spermatogenesis, while the sex accessory organs and male characteristics are maintained by the simultaneous administration of testosterone. In the present study, the histology and ultrastructure of parts of the male reproductive tract of rats treated with medroxyprogesterone (Provera, Upjohn) (1 mg/100 g body weight/day) alone and combined with testosterone (15, 30, or 100 μg/100 g/day) were studied following treatment for up to 16 weeks. The testes and epididymides of rats administered Provera alone or Provera and testosterone weighed less than those of control rats. The weights of the accessory glands of rats treated with Provera were greatly reduced; it was possible to maintain them at approximately control levels by simultaneously administering sufficient testosterone (100 μg/100 g body weight/day). The fertility of some of the animals was tested by caging them with female rats, and none of the treated rats tested in this way was fertile. Similar microscopic alterations were present in the testes of animals administered Provera alone or Provera and different levels of testosterone. Spermato-gonia, spermatocytes, and early spermatids were abundant in treated rats and did not show ultrastructural changes. However, many degenerating or necrotic spermatids of the cap phase (approximately stages 6–7 ) and later were present. Late spermatids of the acrosome and maturation phases were rare. Some necrotic spermatids were surrounded by Sertoli cells, and parts of spermatids lay within lysosome-like structures in the cytoplasm of Sertoli cells. Many large lipid droplets were also present in Sertoli cells of treated rats. Leydig cells were smaller in treated animals than in control rats. The results suggest that germ cells can develop up to cap phase spermatids but then undergo degeneration. These alterations in spermatogenesis may be responsible in large part for the antifertility effect of the progestin and androgen combination. Some rats were permitted to recover following the end of treatment. The microscopic appearance of the testis returned to normal within three to six weeks, although epididymal alterations persisted in some animals six weeks after the end of treatment. By 9 to 12 weeks after the end of treatment the reproductive organs had a normal microscopic appearance in all the rats studied.

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