Premium
Leydig cells contribute to the inhibition of spermatogonial differentiation after irradiation of the rat
Author(s) -
Shetty G.,
Zhou W.,
Weng C. C. Y.,
Shao S. H.,
Meistrich M. L.
Publication year - 2016
Publication title -
andrology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.947
H-Index - 43
eISSN - 2047-2927
pISSN - 2047-2919
DOI - 10.1111/andr.12168
Subject(s) - biology , antagonist , endocrinology , cellular differentiation , medicine , testosterone (patch) , sexual differentiation , microbiology and biotechnology , hormone , andrology , receptor , biochemistry , gene
Summary Irradiation with 6 Gy produces a complete block of spermatogonial differentiation in LBNF 1 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 ( LC s) in maintenance of the block in spermatogonial differentiation after exposure to radiation by specifically eliminating functional LC s 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 LC s recovered. When EDS was followed by treatment with Gn RH antagonist and flutamide, sustained spermatogonial differentiation was induced in >70% of tubules within 2 weeks. When EDS was followed by Gn RH 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 LC s contribute to the production of such inhibitory factors. We tested whether insulin‐like 3 ( INSL 3), a LC ‐produced protein whose expression correlated with the block in spermatogonial differentiation, was indeed responsible for the block by injecting synthetic INSL 3 into the testes and knocking down its expression in vivo with si RNA . 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.