Background: Recombinant human interferon alpha (rh-IFN-α) is used therapeutically in
malignant disorders and chronic hepatitis. The phenotypic effects of this drug at the structural levels on testicular tissue were hardly ever addressed. Hence, this work was designed in adult male albino mice to study the phenotypic effects of rh-INF-α-2b on testicular tissue as well as assessing its effects on serum testosterone and gonadotropins levels.
Objective: This research was planned to through light on the effects of interferon-alpha- 2b (IFN-alpha-2b) on the hypothalamic-pituitary-testicular (HPT) axis of the adult male albino mice.
Design: Experimental study.
Setting: National Hepatology and Tropical Medicine Research Institute (NHTMRI). The study was conducted from November (2004) to February (2005).
Materials and methods: Thirty sexually mature male mice were divided into three groups (10 mice in each group), namely: the control, the experimental and the recovery groups. Mice in the experimental and recovery groups were administered recombinant human interferon alpha intraperitoneally at a dose of 3000 U / mouse weekly for 12 weeks in a volume of 1.0-microliter isotonic normal saline, then animals in the recovery group were left to recover for a further period of two months. At the end of the experiment, serum concentrations of gonadotropins and testosterone were measured and then all animals were then sacrificed to study histopathologically the possible effects of interferon on the testicular tissue.
Results: rh-IFN-α-2b induced remarkable decline in the serum levels of both follicle stimulating hormone (FSH) and luteinizing hormone (LH) in mice of the experimental group compared to the corresponding control and mice of recovery group. At the same time, testosterone was moderately increased in the experimental group, and then returned to its normal levels within 2 months after cessation of treatment. Histopathologically, in the experimental group, there were focal thickening of the basement membrane, degenerative changes and clumping of the germinal epithelial cells in the center of seminiferous tubules, partial desquamation of the germinal epithelium from basement membrane, reduction in the germ cell height, partial arrest of maturation and increased number of Sertoli cells. Increased number of Leydig's cells and hypervascularity were detected in the interstitial spaces. In the recovery group, there was lessening of the germ cell hypoplasia manifested by restoration of spermatogenic cells and accidental disruption in the basement membrane. Most of the spermatogenic and Sertoli cells restored their polarity, height and maturation.
Conclusion: our results suggest that rh-INF-α-2b temporally affects the hypothalamic- pituitary-testicular axis (HPT), both centrally and peripherally (at the testicular level), through the lessening of FSH, LH, raise of testosterone serum levels and direct phenotypic effect on the testicular tissue.
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