Maternal nicotine exposure increases oxidative stress in the offspring.
Fetal and neonatal nicotine exposure causes beta-cell apoptosis and loss of beta-cell mass, but the underlying mechanisms are unknown. The goal of this study was to determine whether maternally derived nicotine can act via the pancreatic nicotinic acetylcholine receptor (nAChR) during fetal and neonatal development to induce oxidative stress in the pancreas. Female Wistar rats were given saline or nicotine (1 mg/kg/day) via subcutaneous injection for 2 weeks prior to mating until weaning (postnatal day 21). In male offspring, nAChR subunit mRNA expression was characterized in the developing pancreas and various oxidative stress markers were measured at weaning following saline and nicotine exposure. The nAChR subunits alpha2-alpha4, alpha6, alpha7, and beta2-beta4 were present in the pancreas during development. Fetal and neonatal exposure to nicotine significantly increased pancreatic GPx-1 and MnSOD protein expression, as well as islet ROS production. Furthermore, protein carbonyl formation was higher in nicotine-exposed offspring relative to controls, particularly within the mitochondrial fraction. There was also a nonsignificant trend toward higher serum 8-isoPG levels. These data suggest that beta-cell apoptosis in the fetal and neonatal pancreas may be the result of a direct effect of nicotine via its receptor and that this effect may be mediated through increased oxidative stress.
Bruin
Jennifer E
JE
Reproductive Biology Division, Department of Obstetrics and Gynecology, McMaster University, Hamilton, Ontario, Canada L8N 3Z5.
Petre
Maria A
MA
Lehman
Megan A
MA
Raha
Sandeep
S
Gerstein
Hertzel C
HC
Morrison
Katherine M
KM
Holloway
Alison C
AC
D000818:Animals; D000831:Animals, Newborn; D000975:Antioxidants / Q000378:metabolism; D015153:Blotting, Western; D005260:Female; D018811:Maternal Exposure; D009538:Nicotine / Q000009:adverse effects* / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000009:adverse effects* / Q000494:pharmacology; D018384:Oxidative Stress; D010179:Pancreas; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species; D011978:Receptors, Nicotinic / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000975:Antioxidants; D018722:Nicotinic Agonists; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D011978:Receptors, Nicotinic; D009538:Nicotine