Maternal methamphetamine administration during pregnancy influences on fetal rat heart development. [corrected].
Methamphetamine (MAP) is one of the most abused drugs in Japan. The rate of MAP abuse by young women has recently reached more than 50 percent in adolescents. A major health concern is that these women will continue to use MAP during pregnancy. The purpose of this study was to investigate whether MAP administered to the mother during pregnancy would change the expression of alpha- and beta- myosin heavy chain (MHC) mRNA in rat neonatal hearts, as detected by quantitative RT-PCR. In addition, morphological changes in the rat neonatal ventricles were examined. Pregnant rats were injected intraperitoneally with MAP (1 mg/kg/day) starting at day 0 of gestation and ending at day 21. There was a significant increase in alpha-MHC mRNA expression in the neonatal ventricular muscle in the experimental group compared with the control at postnatal day (P) 0 and 5. alpha-MHC mRNA expression in both groups was similar after P9. beta-MHC mRNA expression was similar in both groups at P0. Postnatal beta-MHC mRNA expression decreased rapidly, but significant alteration was not detected. Neonatal rats at P0 exhibited some cardiac changes, including hypertrophy, degeneration, and disarrangement of myofibers, but these lesions disappeared by P14. We conclude that chronic maternal administration of MAP changes the alpha- and beta-MHC mRNA expression pattern in fetal and neonatal hearts, correlating with abnormal development, plasma level of hormones, and myocardial damage. At the same time, it is indicated that neonatal cardiomyocytes have reversibility.
Inoue
Hiromasa
H
Department of Legal Medicine, Course of Social Medicine, Osaka University Graduate School of Medicine, 2-2-F3, Yamada-oka, Suita, Osaka 565-0871, Japan. inoueh@forensic.med.kyushu-u.ac.jp
Nakatome
Masato
M
Terada
Masaru
M
Mizuno
Mizuki
M
Ono
Reiko
R
Iino
Morio
M
Ino
Yukiko
Y
Ogura
Yoshiaki
Y
Kuroki
Hisanaga
H
Matoba
Ryoji
R
D000293:Adolescent; D018759:Adrenergic Uptake Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D005260:Female; D005333:Fetus / Q000187:drug effects* / Q000502:physiology; D006321:Heart / Q000196:embryology* / Q000254:growth & development / Q000502:physiology; D006801:Humans; D008297:Male; D008694:Methamphetamine / Q000008:administration & dosage / Q000494:pharmacology*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D018995:Myosin Heavy Chains / Q000235:genetics / Q000378:metabolism; D011247:Pregnancy; D011374:Progesterone / Q000097:blood; D051381:Rats; D017208:Rats, Wistar; D013739:Testosterone / Q000097:blood
D018759:Adrenergic Uptake Inhibitors; D013739:Testosterone; D008694:Methamphetamine; D011374:Progesterone; D018995:Myosin Heavy Chains