Nicotine-induced prenatal overexposure to maternal glucocorticoid and intrauterine growth retardation in rat.
Overexposure to glucocorticoid during fetal development can result in intrauterine growth retardation (IUGR) as well as other diseases after birth. The purpose of this study is to investigate the possibility of glucocorticoid disturbance-mediated nicotine-induced IUGR after chronic prenatal exposure. Nicotine at 1.0mg/kg twice a day was administered subcutaneously to pregnant rats from gestational day (GD) 8 to GD 15 (mid-gestation) or GD 21 (late-gestation). Placental weights and fetal developmental parameters were recorded. Corticosterone levels were determined by radioimmunoassay. The mRNA expressions of adrenal steroidogenic acute regulatory protein (StAR), cytochrome P450 cholesterol side chain cleavage (P450scc) and placental 11 beta-hydroxysteroid dehydrogenase type 2 (11 beta-HSD-2) were determined using real-time quantitative RT-PCR. The results showed that prenatal chronic nicotine exposure causes IUGR in rats (P<0.01); in response to nicotine exposure, maternal serum corticosterone levels were elevated at mid- and late-gestations (P<0.05); mRNA expressions of StAR and P450scc increased in maternal adrenals (P<0.05 or 0.01) but decreased in fetal adrenals (P=0.16 or 0.11). Furthermore, the mRNA levels of placental 11 beta-HSD-2 were reduced at mid- and late-gestations (P<0.05). These results suggest that nicotine-induced IUGR is associated with the disturbances of glucocorticoid homeostasis in maternal and fetal rats. A possible underlying mechanism is that long term nicotine administration leads to fetal overexposure to maternal glucocorticoid by the combined effect of increased maternal glucocorticoid level and impaired placental barrier to it, all of which eventually leads to the fetal adrenocortical dysfunction and IUGR.
Chen
Man
M
Department of Pharmacology, Basic Medical School of Wuhan University, Donghu Road 115(#) Hubei Province Wuhan 430071, China.
Wang
Ting
T
Liao
Zhang-Xiu
ZX
Pan
Xiao-Liang
XL
Feng
Ying-Hong
YH
Wang
Hui
H
D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2 / Q000235:genetics / Q000378:metabolism; D000311:Adrenal Glands / Q000187:drug effects / Q000196:embryology / Q000378:metabolism; D000818:Animals; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000235:genetics / Q000378:metabolism; D003345:Corticosterone / Q000097:blood*; D004195:Disease Models, Animal; D005260:Female; D047109:Fetal Development / Q000187:drug effects; D005317:Fetal Growth Retardation / Q000139:chemically induced* / Q000473:pathology; D020567:Fetal Weight / Q000187:drug effects; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D007279:Injections, Subcutaneous; D018811:Maternal Exposure; D008431:Maternal-Fetal Exchange / Q000187:drug effects* / Q000502:physiology; D009538:Nicotine / Q000633:toxicity*; D018722:Nicotinic Agonists / Q000633:toxicity*; D009929:Organ Size / Q000187:drug effects; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D010920:Placenta / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D013047:Specific Pathogen-Free Organisms; D000098682:Steroidogenic Acute Regulatory Protein
D018722:Nicotinic Agonists; D010750:Phosphoproteins; D000098682:Steroidogenic Acute Regulatory Protein; D009538:Nicotine; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2; D002786:Cholesterol Side-Chain Cleavage Enzyme; D003345:Corticosterone