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

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

Research output: Contribution to journalArticleResearchpeer-review

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.

Original languageEnglish
Article numbere14273
Number of pages16
JournalPhysiological Reports
Volume7
Issue number21
DOIs
Publication statusPublished - 1 Nov 2019
Externally publishedYes

Keywords

  • Alcohol
  • aquaporin-2
  • kidney
  • renal function

Cite this

Dorey, E. S., Walton, S. L., Kalisch-Smith, J. I., Paravicini, T. M., Gardebjer, E. M., Weir, K. A., Singh, R. R., Bielefeldt-Ohmann, H., Anderson, S. T., Wlodek, M. E., & Moritz, K. M. (2019). Periconceptional ethanol exposure induces a sex specific diuresis and increase in AQP2 and AVPR2 in the kidneys of aged rat offspring. Physiological Reports, 7(21), [e14273]. https://doi.org/10.14814/phy2.14273