Differential susceptibility of rat embryos to methyl methanesulfonate during the pregastrulation period.
The effects of exposure of pregnant rats to methyl methanesulfonate (MMS), an alkylating agent, during the pregastrulation period on embryonic and placental development were investigated. SD rats were treated orally with a single dose of MMS (200 mg/kg) in the morning of gestation days 0, 1, 2, 3, 4, 5, or 6 (GD0 to GD6 groups, respectively). The uterine contents including fetuses and placentas of the dams were examined on gestation day 20. The individual fetuses and placentas were weighed, and the fetuses were examined for external, visceral and skeletal anomalies. The progress of ossification was also evaluated. Both pre- and postimplantation embryonic mortalities were higher in the GD0 group than in the control group. The postimplantation loss was also increased for the GD3, GD4 and GD6 groups. Fetal malformations were rare in survivors of all the MMS-treated groups. Intrauterine growth retardation was apparent for fetuses in groups GD5 and GD6. In addition, placental weight was reduced in the GD6 group, but it was increased in the GD0 group. Effects of MMS on embryonic mortality or on fetal or placental growth were absent or minimal in the GD1 and GD2 groups. These results suggest that the susceptibility of rat embryos to MMS varies during the pregastrulation period.
Yokoi
Ryohei
R
Interdisciplinary Graduate School of Science and Technology, Shinshu University, Nagano, Japan. ryohei_yokoi@pharm.kissei.co.jp
Suda
Satoshi
S
Kobayashi
Kazuo
K
Kuroda
Junji
J
Kusama
Hiroshi
H
Kagami
Hiroshi
H
Ono
Tamao
T
D000014:Abnormalities, Drug-Induced; D000284:Administration, Oral; D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage / Q000633:toxicity*; D001755:Blastocyst / Q000187:drug effects*; D001842:Bone and Bones / Q000002:abnormalities / Q000187:drug effects; D002585:Cesarean Section; D020964:Embryo Loss / Q000139:chemically induced*; D004622:Embryo, Mammalian / Q000187:drug effects; D047108:Embryonic Development / Q000187:drug effects; D005260:Female; D005298:Fertility / Q000187:drug effects; D005317:Fetal Growth Retardation / Q000139:chemically induced*; D020567:Fetal Weight / Q000187:drug effects; D005865:Gestational Age; D006801:Humans; D008741:Methyl Methanesulfonate / Q000008:administration & dosage / Q000633:toxicity*; D010012:Osteogenesis / Q000187:drug effects; D010920:Placenta / Q000187:drug effects* / Q000473:pathology; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D014781:Viscera / Q000002:abnormalities / Q000187:drug effects
D018906:Antineoplastic Agents, Alkylating; D008741:Methyl Methanesulfonate