Leydig cells contribute to the inhibition of spermatogonial differentiation after irradiation of the rat

Abstract

SUMMARY Irradiation with 6 Gy produces a complete block of spermatogonial differentiation in LBNF1 rats that would be permanent without treatment. Subsequent suppression of gonadotropins and testosterone (T) restores differentiation to the spermatocyte stage; however this process requires 6 weeks. We evaluated the role of Leydig cells (LCs) in maintenance of the block in spermatogonial differentiation after radiation exposure by specifically eliminating functional LCs with ethane dimethane sulfonate (EDS). EDS (but not another alkylating agent), given at 10 weeks after irradiation, induced spermatogonial differentiation in 24% of seminiferous tubules 2 weeks later. However differentiation became blocked again at 4 weeks as LCs recovered. When EDS was followed by treatment with GnRH antagonist and flutamide, sustained spermatogonial differentiation was induced in >70% of tubules within 2 weeks. When EDS was followed by GnRH antagonist plus exogenous T, which also inhibits LC recovery but restores follicle stimulating hormone (FSH) levels, the spermatogonial differentiation was again rapid but transient. These results confirm that the factors that block spermatogonial differentiation are indirectly regulated by T and probably FSH and that adult and possibly immature LCs contribute to the production of such inhibitory factors. We tested whether insulin-like 3 (INSL3), a LC-produced protein whose expression correlated with the block in spermatogonial differentiation, was indeed responsible for the block by injecting synthetic INSL3 into the testis and knocking down its expression in vivo with siRNA. Neither treatment had any effect on spermatogonial differentiation. The Leydig cell products that contribute to the inhibition of spermatogonial differentiation in irradiated rats remain to be elucidated.

The radioprotective role of Aphanizomenon flos-aquae (AFA) on testis of adult male albino rats

“…They have significant amounts of lipid, protein, chlorophyll, carotenoids, vitamins, minerals and unique pigments. They may also have potent probiotic compounds that enhance health (Singh et al, 2005;Wu et al, 2012). Aphanizomenon flos-aquae (AFA), is a fresh water unicellular blue-green algae that spontaneously grows in Upper Klamath Lake (Germany) and that is consumed as a nutrient-dense food source and for its healthenhancing properties (Pugh and Pasco, 2001).…”

Cryptorchidism after the Fukushima Daiichi Nuclear Power Plant accident:causation or coincidence?

“…Delic et al reported that spermatogenic damage was observed after doses of 3 -5 Gy but not after doses of 0 -2 Gy to adult rat testes 21) . Furthermore, Shetty et al reported that irradiation with 6 Gy caused a complete block of spermatogonia differentiation in LBNF1 rats 22) . Among nonhuman primates, macaques have the most histologically similar testes to humans, and showed a disturbance of spermatogenesis after 2 or 4 Gy that lasted 6 months until recovery, with incomplete recovery even after 18 months 23 -25) .…”

“…(1) Effects of radiation on spermatogenesis Radiation deletes germ cells and can result in permanent azoospermia, suggesting that it can lead to male infertility 20) . There is also some evidence of association between radiation exposure and the impairment of spermatogenesis in rodents and humans.…”

Role of the Hedgehog Signaling Pathway in Regulating the Behavior of Germline Stem Cells

“…In addition, it has been reported that some undefined products seem to contribute to the inhibition of spermatogonial differentiation in irradiated rats [ 33 ]. Hence, during the process of SSC proliferation and differentiation, the balance between SCs and LCs regulated by Hh signaling is crucial [ 36 ] ( Figure 1 , arrowhead in blue).…”