INTERFERON Α-2b MAY IMPAIR TESTICULAR HISTOLOGY INCLUDING SPERMATOGENESIS IN a RAT MODEL

Abstract

Interferon-alpha has been used in various diseases at the reproductive ages. However, the effect of interferon-alpha on testicular histology has not been studied in literature. The aim of this study was to investigate the effects of interferon alpha-2B on testicular histology including spermatogenesis in a rat model. Seventeen adult male Wistar albino rats were divided into 3 groups: Six rats received 7.500 units (5 MIU/m2) of interferon alpha-2B (Intron), considered clinical treatment dose range. Six rats received 30.000 units (20 MIU/m2) of interferon alpha-2B (Intron), considered high treatment dose. Five rats served as a control group receiving 0.5 mL of saline injection. All injections were done intraperitoneally 3 times weekly for 3 weeks under inhalation anesthesia. All rats underwent bilateral orchiectomy 30 days after the experiment. Histological examination included the mean seminiferous tubular diameter (STD), germinal epithelial cell thickness (GECT), and testicular biopsy score (TBS). The mean STD was significantly lower in the low-dose interferon and high-dose interferon groups than in the control group (p = 0.008 and p = 0.004, respectively). The mean GECT was significantly lower in the low-dose interferon and high-dose interferon groups than in the control group (p = 0.008 and p = 0.004, respectively). The mean TBS was significantly lower in the low-dose interferon group (p = 0.05) and the high-dose interferon group (p = 0.01) than in the control group. The decreases in the mean values of the STD, GECT and TBS were not related to the interferon dose. Interferon alpha-2B may impair testicular histology even in clinical widely used treatment dose. Therefore, men at the reproductive ages should be fully informed for the use of interferon-alpha in the treatment of various diseases.

Excess Type I Interferon Signaling in the Mouse Seminiferous Tubules Leads to Germ Cell Loss and Sterility

“…Although this strong innate immune response is likely to be critical in impairing viral replication, it may also impact upon the normal functioning of the testis. In line with this, intraperitoneal injections of IFN␣ have been shown to induce impaired spermatogenesis in rats (13), whereas in infertile men, the presence of high levels of IFN␣ was detected in the semen (14). In 1988, two transgenic studies reported sterility in male mice overexpressing IFN␣ or IFN␤ (15,16).…”

Ribavirin and pegylated interferon treatment for hepatitis C was associated not only with semen alterations but also with sperm deoxyribonucleic acid fragmentation in humans

“…Two studies in rats have reported discrepant results. Hibi et al (16) found no alterations in epididymal sperm count or motility, and Ulusoy et al (17) found testicular histology modifications, but these were not related to interferon dose. On the other hand, one case report has shown azoospermia and high FSH level in a man receiving interferon (18), whereas a study in 12 patients under interferon therapy did not show any inhibin decrease (19).…”

Effect of terpenoidal fraction of Echinops echinatus roots on reproductive parameters of male rats

“…Three slides from the upper, lower and mid portions of the testis were prepared and evaluated for each testis. The mean STD and GECT were determined in 20 seminiferous tubules of each section using a projection microscope [15], and the values were expressed in terms of micrometers (lm). Microphotographs were made using an Olympus BX 40 microscope attached to an Olympus DP12 digital camera.…”