Similarities and differences in the in vivo response of mouse neonatal gonocytes and spermatogonia to genotoxic stress.
Neonatal gonocytes are the precursors of both spermatogonial stem cells and spermatogonia; thus, any persistent DNA damage in these cells may lead to heritable mutations. We investigated the response of male mouse neonatal germ cells to ionizing radiation. Both gonocytes and spermatogonia died in large numbers by apoptosis. However, we found that the gonocytes were significantly more sensitive than spermatogonia and somatic cells to radiation-induced double-strand breaks (DSBs), as assayed by the number of gamma-H2AFX foci. In contrast, gonocytes irradiated in G2 phase seemed to repair DSBs faster than spermatogonia. Moreover, when irradiated in S phase, gonocytes arrested their cell cycle at the G1/S phase transition, whereas spermatogonia were mostly blocked in G2/M phase. Despite these differences, both cell types expressed high levels of proteins involved in DSB signaling and repair. Within the first hours after irradiation, the expression of Atr, Mre11a, H2afx, Xrcc6, and Xrcc4 was downregulated in neonatal spermatogonia, whereas, in gonocytes, most gene expression was unaffected. Together, these results suggest that the response of neonatal testis to genotoxic stress is regulated by different mechanisms according to the cell type and the differentiation status.
Forand
Anne
A
French Atomic Energy Commission, Fontenay aux Roses, France.
Fouchet
Pierre
P
Lahaye
Jean-Baptiste
JB
Chicheportiche
Alexandra
A
Habert
René
R
Bernardino-Sgherri
Jacqueline
J
D000818:Animals; D000831:Animals, Newborn; D001483:Base Sequence; D002453:Cell Cycle / Q000528:radiation effects; D002454:Cell Differentiation; D053903:DNA Breaks, Double-Stranded; D017931:DNA Primers / Q000235:genetics; D004260:DNA Repair / Q000235:genetics; D015870:Gene Expression / Q000528:radiation effects; D006657:Histones / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D011836:Radiation Tolerance; D013093:Spermatogonia / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects*; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects*
D017931:DNA Primers; D006657:Histones; C475961:gamma-H2AX protein, mouse