Fetal and neonatal nicotine exposure and postnatal glucose homeostasis: identifying critical windows of exposure.
Fetal and lactational exposure to nicotine at concentrations comparable with those in women who smoke causes impaired glucose tolerance in male offspring in postnatal life. It remains unknown whether there are critical windows of susceptibility to nicotine exposure. Female nulliparous Wistar rats were given saline vehicle or nicotine bitartrate (1 mg/kg per day) prior to pregnancy, which was then: A) discontinued during pregnancy and lactation; B) continued until parturition; C) continued until weaning; and D) discontinued during pregnancy and restarted from lactation until weaning. At 26 weeks of age, offspring in each group were challenged with an oral glucose load. Beta-cell mass, apoptosis, and proliferation were measured at birth, and at 4 and 26 weeks of age. The animals in group C (exposed to nicotine throughout pregnancy and lactation) had reduced beta-cell mass from birth through 26 weeks of age and impaired glucose homeostasis at 26 weeks of age. beta-Cell mass was also reduced at birth and at 4 weeks of age in animals exposed to nicotine during pregnancy alone (group B). However, enhanced proliferation following weaning led to recovery of this defect to 98% of control levels by week 26. The response to the glucose load in groups A, B, and D did not differ from controls. Continued exposure to nicotine from conception through lactation results in permanent beta-cell loss and subsequent impaired glucose tolerance. This model of type 2 diabetes requires that nicotine exposure occurs both in utero and during lactation.
Bruin
Jennifer E
JE
Reproductive Biology Division, Department of Obstetrics and Gynecology, McMaster University, RM HSC-3N52, 1200 Main Street West, Hamilton, Ontario, Canada L8N 3Z5.
Kellenberger
Lisa D
LD
Gerstein
Hertzel C
HC
Morrison
Katherine M
KM
Holloway
Alison C
AC
D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects; D001786:Blood Glucose / Q000032:analysis; D049109:Cell Proliferation / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2; D005260:Female; D005951:Glucose Tolerance Test; D007333:Insulin Resistance; D050417:Insulin-Secreting Cells / Q000473:pathology; D007774:Lactation; D008297:Male; D008431:Maternal-Fetal Exchange; D023421:Models, Animal; D009538:Nicotine / Q000009:adverse effects* / Q000494:pharmacology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011897:Random Allocation; D051381:Rats
D001786:Blood Glucose; D009538:Nicotine