Prenatal nicotine exposure induced GDNF/c-Ret pathway repression-related fetal renal dysplasia and adult glomerulosclerosis in male offspring

Abstract

Prenatal nicotine exposure could induce fetal renal dysplasia associated with the suppression of the GDNF/c-Ret pathway and adult glomerulosclerosis in male offspring, which might be mediated by alterations in angiotensin II receptors.

The impact of smoking and nicotine exposure during pregnancy on fetal nephrogenesis: a systematic review

“…The most common technique of nicotine exposure was via subcutaneous osmotic mini pumps. Five studies utilised a concentration of 6 mg/kg/day of nicotine, 14,23,26,27,30 two studies utilised a concentration of 1 mg/kg with one study exposing twice daily 21 and the other study exposing once daily 22 ; one study compared concentrations of 1 mg/kg/day, 2 mg/kg/day and 4 mg/kg/day 28 ; and one study exposed 25 mg over 7 days. 25 Two studies utilised inhalation as the mode of nicotine exposure.…”

“…A reduction in fetal kidney size, volume and weight has been linked to smoking during pregnancy in human studies, 4,15,16,32,33 whereas results from animal studies are mixed. 17,20,21 Almost all human studies evaluated either kidney size, volume, weight, or a combination of the three. Statistically significant results were linked to kidney size.…”

“…Methods of exposure included subcutaneous pumps or subcutaneous injections, a chamber where study subjects were exposed to smoke equivalent to five cigarettes, and application of cigarette condensate to the oral mucosa. 14,17,[20][21][22][23][24][25][26][27][28]…”

“…Three articles studied Wistar rats, [20][21][22] five articles studied Sprague-Dawley rats, 14,17,[23][24][25] two articles compared spontaneously hypertensive rats (SHR) to Brown Norway rats (BN), 26,27 one article studied Kunming mice, 28 and one article studied Balb/c mice. 29 Seven studies utilised male rats, [20][21][22][23]26,27,29 three studies did not specify sex, 14,25,28 and two studies utilised both female and male rats, 17,24 but only one study compared results to gender. 24 Across the 12 studies, multiple techniques were utilised to mimic nicotine exposure.…”

“…20 Li G et al demonstrated increased collagen expression in the cigarette and e-cigarette-exposed groups compared to the control (p = <0.01, p = 0.05, respectively), with the cigarette-exposed group also demonstrating increased fibronectin (p = <0.05). 29 Total nephron number, total glomeruli number, and glomerular size were measured in six studies 14,[20][21][22]24,29 and renal nephron endowment was measured in one study. 23 Zarzecki et al compared males and females and found that exposed males had significantly more glomeruli when compared to non-exposed males (p = 0.01).…”