Effects of the Anti-Androgen Flutamide on the Descent of the Testis

Kassim, Normadiah M (1996) Effects of the Anti-Androgen Flutamide on the Descent of the Testis. PhD thesis, University of Glasgow.

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Exposure of male Albino Swiss rats to the non-steroidal anti-androgen flutamide during the period from gestational day 10 to birth resulted in feminization 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 12% of cases, while 44% of testes descended to the scrotum and 44% 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 Sella 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 day 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 i) prenatal flutamide treatment per se has a detrimental effect on adult testis morphology but ii) the degree of abnormality of the testes is strongly influenced by location, and iii) the varying degrees of seminiferous tubule damage are probably due to the stage-specific effects of reduced testicular testosterone on spermatogenesis. The findings of this study also demonstrate that outgrowth of the gubernacular cone is not affected by flutamide; however, the regression phase (which occurs postnatally) was delayed. Furthermore, shortening of the gubernacular cord was inhibited in males treated prenatally with flutamide. Exposure of males rats to anti-androgen flutamide resulted in the persistence of the cranial suspensory ligament. This persistence however, was irrespective of the position of the testes in the adult. Nor was there any difference in the structure of the cranial suspensory ligaments from these varying testis locations. This suggests that retention of the cranial suspensory ligament is not an important factor in testicular maldescent. Prenatal flutamide treatment to rats also interfered with Wolffian duct development since most of the offspring of flutamide-treated mothers exhibited varying degrees of inhibition/absence of Wolffian duct derivatives. Moreover, impaired development of the epididymis and vas deferens was not necessarily associated with testicular maldescent since (despite partial to complete absence of epididymis and vas deferens) 44% of testes descended normally into the scrotum in males treated prenatally with flutamide. In contrast to the rat, prenatal flutamide treatment to hamsters did not interfere with testicular descent although there was clear evidence of flutamide action during development including inhibition of development of the Wolffian duct and retention of cranial suspensory ligament.

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Additional Information: Adviser: A P Payne
Keywords: Endocrinology
Date of Award: 1996
Depositing User: Enlighten Team
Unique ID: glathesis:1996-75851
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 19 Nov 2019 17:43
Last Modified: 19 Nov 2019 17:43
URI: http://theses.gla.ac.uk/id/eprint/75851

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