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23 December 2016 Ovine uterine space restriction causes dysregulation of the renin–angiotensin system in fetal kidneys
Rachel A. Kranch-Shorthouse, Adam S. Bauer, Ronald R. Magness, Gladys E. Lopez, Jeffrey L. Segar, Sharon E. Blohowiak, Pamela J. Kling
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Abstract

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 II1-8 receptor type 1 (AT1R) and type 2 (AT2R), and angiotensin II1-7 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 AT1R, AT2R, and MASR proteins were assessed by Western immunoblotting and immunohistochemistry.

Results: AT1R, AT2R, and MASR protein expression was higher in USR at GD130 than aged-matched NSR and USR at GD120, (P < 0.05 all). AT1R and AT2R 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.

Summary Sentence

Multifetal gestation-induced intrauterine growth restriction alters expression and localization of fetal renal angiotensin receptors and the associated relationships with fetal plasma chemistries.

© 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
Rachel A. Kranch-Shorthouse, Adam S. Bauer, Ronald R. Magness, Gladys E. Lopez, Jeffrey L. Segar, Sharon E. Blohowiak, and Pamela J. Kling "Ovine uterine space restriction causes dysregulation of the renin–angiotensin system in fetal kidneys," Biology of Reproduction 96(1), 211-220, (23 December 2016). https://doi.org/10.1095/biolreprod.116.140079
Received: 20 May 2016; Accepted: 6 December 2016; Published: 23 December 2016
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