The effects of pre‐ and postnatal exposure to the nonsteroidal antiandrogen flutamide on testis descent and morphology in the Albino Swiss rat

Abstract

Exposure of male Albino Swiss rats to the nonsteroidal antiandrogen flutamide during the period from gestational day (d) 10 to birth resulted in feminisation of the external genitalia and the suppression of growth of the male reproductive tract. In adulthood, testes were found to be located in diverse positions. True cryptorchidism occurred in 10 % of cases, whereas 50 % of testes descended to the scrotum and 40 % were located in a suprainguinal ectopic region. Varying degrees of tubule abnormality were seen in the testes of flutamide-treated animals, ranging from completely normal tubules with full spermatogenesis (and the expected frequency of the stages of spermatogenesis) to severely abnormal tubules lined with Sertoli cells only. For each individual testis, the overall severity of tubule damage was strongly correlated with its adult location, with intra-abdominal testes worst affected and scrotally-located testes least ; only the latter contained normal tubules. Similarly, intra-abdominal testes were the smallest in weight and contained the least testosterone. By contrast, postnatal treatment of male rats with flutamide from birth to postnatal d 14 did not impair development of the external genitalia, the process of testicular descent or adult spermatogenesis. These findings confirm that androgen blockade during embryonic development interferes with testicular descent but also demonstrate that (1) prenatal flutamide treatment per se has a detrimental effect on adult testis morphology but (2) the degree of abnormality of the testes is strongly influenced by location.

Effects of Flutamide on Sex Maturation and Behavior of Offspring Born to Female Rats Treated During Late Pregnancy

“…Undescended testes were smaller in weight than descended testes, and the histological degeneration in the testis was attributed to abdominal cryptorchidism. In a study of flutamide-induced cryptorchidism, Kassim et al (1997) found differences in degree of abnormalities of spermatogenesis, depending on the intra-abdominal position of the testes, which support our findings of testicular degeneration being a secondary change due to abdominal cryptorchidism. Association of the testicular hypospermatogenesis and lower number of sperm in the lumen of the epididymal ductules was evidenced by histological findings at the final necropsy .…”

Effects of long-term flutamide treatment during development in zebra finches

“…Flutamide's reduction of testes size in the present study ( Figure 1A) is consistent with its effects in developing rats [5,17]. This reduction in testes size can be explained either by flutamide's direct antiandrogenic effect on the testes or by flutamide's up-regulation of aromatase activity and consequent increased E 2 production [16].…”

Cryptorchidism in common eutherian mammals

“…However, data were available for rats exposed to flutamide from GD 12 to PND 27 or administered flutamide by injection on PND 1-14 (listed under inguinoscrotal migration in Table 1); all testes completed transinguinal migration and were found in the scrotum at 16-20 week of age. Hence, transinguinal migration of testes occurs in rat pups, at the normal time or with slight delay, with testosterone- Barthold et al (1996); (2) Kassim et al (1997); (3) McMahon et al (1995); (4) Mylchreest et al (1999); (5) Shono et al (1994b); (6) Spencer et al (1991); (7) Spencer et al (1993).…”