Periconceptional ethanol exposure induces a sex specific diuresis and increase in AQP2 and AVPR2 in the kidneys of aged rat offspring.

Emily S Dorey,Kristy A Weir,Karen M Moritz,Emelie M Gardebjer,Jacinta I Kalisch‐Smith,Stephen T Anderson,Reetu R Singh,Tamara M Paravicini,Helle Bielefeldt‐Ohmann,Sarah L Walton,Mary E Wlodek

doi:10.14814/phy2.14273

Emily S Dorey, Kristy A Weir + Show 9 more

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https://doi.org/10.14814/phy2.14273

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Abstract

Maternal alcohol consumption can impair renal development and program kidney dysfunction in offspring. Given that most women who drink alcohol cease consumption upon pregnancy recognition, we aimed to investigate the effect of alcohol around the time of conception (PC:EtOH) on offspring renal development and function. Rats received a liquid diet ±12.5% v/v ethanol from 4 days before to 4 days after mating. At postnatal day 30, nephron number was assessed. Urine flow and electrolyte (Na, K, Cl) excretion was measured at 6 and 19 months and blood pressure at 12 months. At 19 months, kidneys were collected for gene and protein analysis and assessment of collecting duct length. At postnatal day 30, PC:EtOH offspring had fewer nephrons. At 6 months, PC:EtOH exposure did not alter urine flow nor affect blood pressure at 12 months. At 19 months, female but not male offspring exposed to PC:EtOH drank more water and had a higher urine flow despite no differences in plasma arginine vasopressin (AVP) concentrations. Aqp2 mRNA and Avpr2 mRNA and protein expression was increased in kidneys from female PC:EtOH offspring but collecting duct lengths were similar. Immunofluorescent staining revealed diffuse cytoplasmic distribution of AQP2 protein in kidneys from PC:EtOH females, compared with controls with apical AQP2 localization. PC:EtOH resulted in a low nephron endowment and in female offspring, associated with age‐related diuresis. Changes in expression and cellular localization of AQP2 likely underpin this disturbance in water homeostasis and highlight the need for alcohol to be avoided in early pregnancy.

Highlights

The incidence of alcohol consumption during pregnancy is high in western countries, with approximately 30% of surveyed women in the United States reporting drinking at some point during their pregnancy compared with 40% of Australian women and up to 80% of women in Ireland (Ethen et al 2009; O’Keeffe et al 2015)
While many women stop or at least reduce their alcohol intake once they are aware of their pregnancy, research shows that approximately half of pregnancies in the United States are unintended and it is likely that many women are exposing their embryos to alcohol prior to pregnancy recognition (Finer and Zolna, 2014)
The expression of AVPR2, the receptor responsible for trafficking of AQP2, was increased in females from PC:EtOH group only, but the phosphorylated AQP2 was not significantly different to control. These results suggest that the increased urine flow in females may be mediated by altered trafficking of AQP2 to the apical membrane of principal cells within the collecting duct

Summary

Introduction

The incidence of alcohol consumption during pregnancy is high in western countries, with approximately 30% of surveyed women in the United States reporting drinking at some point during their pregnancy compared with 40% of Australian women and up to 80% of women in Ireland (Ethen et al 2009; O’Keeffe et al 2015). Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

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