Protection from radiation-induced male germ cell loss by sphingosine-1-phosphate.
Male germ cells are susceptible to radiation-induced injury, and infertility is a common problem after total-body irradiation. Here we investigated, first, the effects of irradiation on germ cells in mouse testis and, second, the role of sphingosine-1-phosphate (S1P) treatment in radiation-induced male germ cell loss. Irradiation of mouse testes mainly damaged the early developmental stages of spermatogonia. The damage was seen by means of DNA flow cytometry 21 days after irradiation as decreasing numbers of spermatocytes and spermatids with increasing amounts of ionizing radiation (0.1-2.0 Gy). Intratesticular injections of S1P given 1-2 h before irradiation (0.5 Gy) did not protect against short-term germ cell loss as measured by in situ end labeling of DNA fragmentation 16 h after irradiation. However, after 21 days, in the S1P-treated testes, the numbers of primary spermatocytes and spermatogonia at G2 (4C peak as measured by flow cytometry) were higher at all stages of spermatogenesis compared with vehicle-treated testes, indicating protection of early spermatogonia by S1P, whereas the spermatid (1C) populations were similar. In conclusion, S1P appears to protect partially (16%-47%) testicular germ cells against radiation-induced cell death. This warrants further studies aimed at development of therapeutic agents capable of blocking sphingomyelin-induced pathways of germ cell loss.
Otala
Marjut
M
Programme for Developmental and Reproductive Biology, Biomedicum Helsinki and Hospital for Children and Adolescents, University of Helsinki, FIN-00029 HUS, Helsinki, Finland.
Suomalainen
Laura
L
Pentikäinen
Markku O
MO
Kovanen
Petri
P
Tenhunen
Mikko
M
Erkkilä
Krista
K
Toppari
Jorma
J
Dunkel
Leo
L
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects*; D004307:Dose-Response Relationship, Radiation; D008246:Lysophospholipids / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008854:Microscopy, Electron; D009929:Organ Size / Q000528:radiation effects; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D013093:Spermatogonia / Q000528:radiation effects* / Q000648:ultrastructure; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D013737:Testis / Q000166:cytology / Q000473:pathology / Q000528:radiation effects
D008246:Lysophospholipids; D011837:Radiation-Protective Agents; C060506:sphingosine 1-phosphate; D013110:Sphingosine