The effect of sustained and local administration of epidermal growth factor on improving bilateral testicular tissue after torsion

Abstract

Epidermal growth factor (EGF) modulates Leydig cell proliferation, steroidogenesis, spermiogenesis, and Sertoli cell activity. It plays an important role in repairing ischemia-reperfusion injury in different tissues. The aim of this study was to evaluate the effects of sustained and local administration of EGF on improving bilateral testicular tissue after torsion. A total of 57 Wistar albino rats were used. For the EGF transport system, 1x2 cm gelatin films containing 2 microg EGF were used. Torsion was created by rotating the right testis 720 degrees in a clockwise direction for 4 h in all groups except the control group. Then, in the torsion group, bilateral orchiectomy was performed. After returning the torsioned ipsilateral testes to their normal state, the bilateral testes were wrapped by 1x2 cm unloaded gelatin films in the gelatin (G7 and G21) groups and, by 2 microg EGF loaded gelatin films in the EGF 7 and EGF 21 groups. The testes were removed on the seventh and 21st days, respectively, for biochemical and histological examination. Histologically, Johnsen's spermatogenesis criteria and mean seminiferous tubule diameter (MSTD) measurements were used. The EGF7 group did not show significant loss of Sertoli cells, while in the G7 group the number of these cells decreased. The ipsilateral ischemic testis of the EGF21 group showed Leydig cell hyperplasia, and the contralateral non-ischemic testes in this group were similar to the control group. In the G21 group, the bilateral testes showed Sertoli cell only syndrome in some sections, and most of the cells were undergoing apoptosis. The mean spermatogenesis scores and MSTD in the EGF7 and EGF21 groups were higher than in the G7 and G21 groups ( P<0.05). Malondialdehyde levels were significantly lower in the EGF groups than in the G groups ( P<0.05). Glutathione peroxidase (GSH-Px) levels in the G21 group were significantly higher than in the EGF21 group. Our study shows that local and sustained EGF release after testicular torsion improves bilateral testicular injury. EGF administration may be a new treatment choice for bilaterally injured testis after detorsion without removing the twisted testis.

Effects of experimental diabetes on testis proliferations and apoptosis in rats

“…In the present study, the lowest MTBS values in testes were found in diabetic group. Another histoAktas et al pathological criterion of testicular damage used in the present study was the MSTD value, which is also used in the scientific literature to estimate testicular tissue damage (Uguralp et al, 2004). In the present study, the lowest MSTD value was also observed in diabetic group, which is similar to results obtained for MTBS values and is in accordance with previous studies (Altay et al, 2003).…”

“…It is based on the evaluation of progressive degeneration of the germinal epithelium (Johnsen, 1970;Uguralp et al, 2004). In the present study, the lowest MTBS values in testes were found in diabetic group.…”

Endogenous EGF maintains Sertoli germ cell anchoring junction integrity and is required for early recovery from acute testicular ischemia/reperfusion injury

“…EGF significantly protects against intestinal IR injury. Sustained administration of EGF after testicular torsion improves bilateral testicular injury (Uguralp et al 2004). Moreover, emerging evidences demonstrated that EGF signaling is able to decrease ROS production, which has been suggested to play an important role during IR pathogenesis, in the intestine, pancreas, and renal tissue (Maeda et al 2004, Hussein Ael et al 2011.…”

“…The EGF-GF ligands, EGF, transforming growth factor-a, and b-cellulin stimulate DNA synthesis in microdissected stage I segments of rat testis seminiferous tubules in vitro (Wahab-Wahlgren et al 2003). More recently, it has been shown that supplement of exogenous EGF after testicular torsion improves bilateral testicular injury (Uguralp et al 2004). Given the anti-apoptotic/ proapoptotic effect of EGF signaling is highly dose dependent (usually low concentrations of EGF promoted proliferation, while high concentrations of EGF induced cell cycle arrest, inhibition of proliferation, and apoptosis) (Zhao et al 2006), we hypothesize that the endogenous EGF may play an important role during the pathogenesis of testicular IR injury.…”

Functional characteristics of ram cooling-stored spermatozoa under the influence of epidermal growth factor

“…Although the EGF receptors in spermatozoa of several mammalian species have been demonstrated (Naz and Minhas 1995), the role of EGF in sperm function regulation is not ascertained (Oliva-Hernandez and Perez-Gutierrez 2008). Lack of EGF in plasma of mouse males led to the decrease in sperm concentration and motility (Liu et al 1994), whilst the administration of exogenous EGF was useful for repair of testicular disorders (Uguralp et al 2004;Kurokawa et al 2005) or for the treatment of male infertility in rodents (Cheng et al 2006). EGF regulates sperm functions (capacitation, acrosome reaction) through the activation of tyrosine kinase (Furuya et al 1993a;Naz and Kaplan 1993) or protein kinase C (Lax et al 1994), which are activated by specific EGF receptors demonstrated in several animal species (Naz and Ahmad 1992;Naz and Minhas 1995;Oliva-Hernandez and Perez-Gutierrez 2008).…”