

Periconceptional alcohol exposure alters female kidney function and circadian regulation of renal gene expression (#344)

Emily S Dorey 1 , Diana Lucia 1 , Michael Wing 1 , James SM Cuffe 1 , Samantha Craven 1 , Katelyn Hafey 1 , Mary E Wlodek 2 , Karen M Moritz 1 3
  2. The University of Melbourne, Melbourne, VIC, Australia
  3. Child Health Research Centre, The University of Queensland, Brisbane

Introduction: Alcohol exposure throughout gestation has been shown alter kidney development and function. Although many women decrease consumption of alcohol upon pregnancy recognition, exposure during the periconceptional period (PC) is common.  Many genes that regulate renal function are expressed in a circadian manner.  This study aimed to investigate the effect of periconceptional alcohol exposure (PC:EtOH) on renal function in offspring and if the renal circadian clock was altered.  

Methods: Female Sprague Dawley rats received a control liquid diet or 12.5%v/v ethanol diet (PC:EtOH) for four days before and after mating. In cohort 1, at 19 months (m) male and female offspring underwent 24hour metabolic cage studies to examine renal function and plasma aldosterone was measured by ELISA. Kidneys from a second cohort of female offspring were collected at 5m at six Zeitgeiber times (ZT). Renal mRNA expression of clock circadian regulator (Clock), period circadian regulator 1 (Per1), nuclear receptor subfamily 3 group C member 2 (MR) and epithelium sodium channel alpha subunit (αEnac) were analysed using cosinor analysis.

Results: At 19m, PC:EtOH exposure increased urine flow and water consumption, with post-hoc analysis showing the increase in female offspring only (PTrt<0.05, P<0.05). PC:EtOH decreased plasma aldosterone levels (PTrt<0.05). At 5m, following Cosinor analysis, PC:EtOH exposure shifted the acrophase (time of peak expression) of Clock, Per1, MR and αEnac (P<0.05).  PC:EtOH decreased mRNA expression of MR and αEnac at ZT2.5 (P<0.05) and αEnac and Clock at ZT6.5 (P<0.05).

Conclusion: PC:EtOH causes diuresis in 19m female offspring associated with reduced plasma aldosterone and altered circadian expression of genes involved in renal function at 5m. Aldosterone is known to affect mRNA expression of MR as well as Per1, which regulates αEnac in the kidney. Together, this study demonstrates altered renal function in female PC:EtOH could be directly influenced by the renal circadian clock.