PMID- 28395333 OWN - NLM STAT- MEDLINE DCOM- 20171128 LR - 20200403 IS - 1529-7268 (Electronic) IS - 0006-3363 (Print) IS - 0006-3363 (Linking) VI - 96 IP - 1 DP - 2017 Jan 1 TI - Ovine uterine space restriction causes dysregulation of the renin-angiotensin system in fetal kidneys. PG - 211-220 LID - 10.1095/biolreprod.116.140079 [doi] AB - In ovine pregnancy, uterine space restriction (USR) resulting from decreased space for placental attachment caused intrauterine growth restriction and impaired nephrogenesis. The fetal kidney renin-angiotensin system (RAS) is involved in nephrogenesis, fluid balance, and iron deposition. Angiotensin II exerts its effects via multiple receptors: angiotensin II 1-8 receptor type 1 (AT 1 R) and type 2 (AT 2 R), and angiotensin II 1-7 Mas receptor (MASR). OBJECTIVE: : To test the hypothesis that ovine USR is associated with dysregulation of the fetal renal RAS. METHODS: : Multiparous pregnant ewes (n = 32), 16 with surgical bifurcated disconnection of one uterine horn to further reduce placental attachment sites, were studied. USR (n = 31) ovine fetuses were compared to nonspace restricted (NSR) singleton controls (n = 22) on gestational day (GD) 120 or GD130, term GD147. Fetal plasma was collected to evaluate plasma renin activity and iron indices. Fetal kidney AT 1 R, AT 2 R, and MASR proteins were assessed by Western immunoblotting and immunohistochemistry. RESULTS: : AT 1 R, AT 2 R, and MASR protein expression was higher in USR at GD130 than aged-matched NSR and USR at GD120, ( P < 0.05 all). AT 1 R and AT 2 R localization was homogenous throughout proximal and distal tubules in both USR and NSR at both gestational dates. MASR localization was punctate throughout renal cortical structures including tubules and glomeruli in both USR and NSR, shifted to intranuclear at GD130. Plasma renin activity was inversely related to plasma osmolarity ( P < 0.02) and was downregulated in USR at GD130 ( P < 0.05). CONCLUSIONS: : By late gestation, USR upregulated renal angiotensin receptor expression, an effect with potential functional implications. CI - (c) The Authors 2016. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please journals.permissions@oup.com FAU - Kranch-Shorthouse, Rachel A AU - Kranch-Shorthouse RA AD - Department of Pediatrics, University of Wisconsin-Madison, Wisconsin, USA. AD - Department of Nutritional Science, The University of Arizona, Arizona, USA. FAU - Bauer, Adam S AU - Bauer AS AD - Department of Pediatrics, University of Wisconsin-Madison, Wisconsin, USA. FAU - Magness, Ronald R AU - Magness RR AD - Department of Pediatrics, University of Wisconsin-Madison, Wisconsin, USA. AD - Department of Obstetrics and Gynecology, University of Wisconsin-Madison, Wisconsin, USA. AD - Department of Animal Sciences, University of Wisconsin-Madison, Wisconsin, USA. AD - Department of Obstetrics and Gynecology, University of South Florida, Florida, USA. FAU - Lopez, Gladys E AU - Lopez GE AD - Department of Obstetrics and Gynecology, University of Wisconsin-Madison, Wisconsin, USA. FAU - Segar, Jeffrey L AU - Segar JL AD - Department of Pediatrics, University of Iowa, Iowa, USA. FAU - Blohowiak, Sharon E AU - Blohowiak SE AD - Department of Pediatrics, University of Wisconsin-Madison, Wisconsin, USA. FAU - Kling, Pamela J AU - Kling PJ AD - Department of Pediatrics, University of Wisconsin-Madison, Wisconsin, USA. LA - eng GR - R01 HL117341/HL/NHLBI NIH HHS/United States GR - R01 HL049210/HL/NHLBI NIH HHS/United States GR - R01 HL087144/HL/NHLBI NIH HHS/United States PT - Journal Article PL - United States TA - Biol Reprod JT - Biology of reproduction JID - 0207224 RN - 0 (Receptors, Angiotensin) RN - AYI8EX34EU (Creatinine) RN - E1UOL152H7 (Iron) RN - EC 3.4.23.15 (Renin) SB - IM MH - Animals MH - Creatinine/blood MH - Disease Models, Animal MH - Female MH - Fetal Growth Retardation/*metabolism MH - Iron/metabolism MH - Kidney Cortex/*metabolism MH - Osmolar Concentration MH - Pregnancy MH - Receptors, Angiotensin/*metabolism MH - Renin/blood MH - *Renin-Angiotensin System MH - Sheep PMC - PMC6373835 OTO - NOTNLM OT - IUGR OT - RAS OT - developmental programming OT - renal development EDAT- 2017/04/11 06:00 MHDA- 2017/11/29 06:00 PMCR- 2018/01/01 CRDT- 2017/04/11 06:00 PHST- 2016/05/20 00:00 [received] PHST- 2016/12/06 00:00 [accepted] PHST- 2017/04/11 06:00 [entrez] PHST- 2017/04/11 06:00 [pubmed] PHST- 2017/11/29 06:00 [medline] PHST- 2018/01/01 00:00 [pmc-release] AID - 2734428 [pii] AID - bio140079 [pii] AID - 10.1095/biolreprod.116.140079 [doi] PST - ppublish SO - Biol Reprod. 2017 Jan 1;96(1):211-220. doi: 10.1095/biolreprod.116.140079.