Ethylnitrosourea-induced apoptosis in primordial germ cells of the rat fetus.
Ethylnitrosourea (ENU) is a simple alkylating agent. It induces gene mutations in fetal primordial germ cells (PGCs), and a high incidence of congenital malformations is also found in the offspring of male mice treated with ENU at the embryonic stage. It is also reported that decreases in the fertility rate and weights of the testis and ovary were found in the offspring from dams treated with ENU. In this study, we analyzed the occurrence of apoptotic cell death and the expression of p53 protein which is thought to play an important role in the DNA damage-induced apoptosis after administration of ENU to pregnant rats on day 13 of gestation to obtain a clue for clarifying the toxic effect of ENU on PGCs. Apoptotic cells increased in PGCs in fetal gonads from 3 h after treatment. The number of apoptotic PGCs peaked at 6 h and gradually decreased towards 24 h after treatment. On the other hand, p53-positive PGCs increased from I h after treatment, prior to the induction of apoptosis. The number of p53-positive PGCs peaked at 3 h and returned to the control level at 24 h after treatment. These results suggest that ENU induces apoptosis in rat fetal PGCs immediately after its administration to dams and excess cell death by apoptosis may have a close relation to the later occurrence of decreases in the fertility rate and gonadal weight. Moreover, a possible involvement of p53 is suggested in the ENU-induced apoptosis in PGCs.
Katayama
Kei-ichi
K
Department of Veterinary Pathology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan. aa07188@mail.ecc.u-tokyo.ac.jp
Ueno
Masaki
M
Yamauchi
Hirofumi
H
Nakayama
Hiroyuki
H
Doi
Kunio
K
D000477:Alkylating Agents / Q000633:toxicity*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053938:DNA Fragmentation / Q000187:drug effects*; D005038:Ethylnitrosourea / Q000633:toxicity*; D005260:Female; D005333:Fetus / Q000187:drug effects* / Q000473:pathology; D005854:Germ Cells / Q000378:metabolism / Q000648:ultrastructure*; D006066:Gonads / Q000196:embryology / Q000648:ultrastructure; D008297:Male; D011247:Pregnancy; D051381:Rats; D011916:Rats, Inbred F344; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis
D000477:Alkylating Agents; D016159:Tumor Suppressor Protein p53; D005038:Ethylnitrosourea