Hyperuricemia during Pregnancy Leads to a Preeclampsia-Like Phenotype in Mice

Benjamin P Lüscher; Andreina Schoeberlein; Daniel V Surbek; Marc U Baumann

doi:10.3390/cells11223703

Hyperuricemia during Pregnancy Leads to a Preeclampsia-Like Phenotype in Mice

Cells. 2022 Nov 21;11(22):3703. doi: 10.3390/cells11223703.

Authors

Benjamin P Lüscher^{1

2}, Andreina Schoeberlein^{1

2}, Daniel V Surbek^{1

2}, Marc U Baumann^{1

2}

Affiliations

¹ Department of Obstetrics and Gynecology, Inselspital, Bern University Hospital, 3010 Bern, Switzerland.
² Department for BioMedical Research (DBMR), University of Bern, 3010 Bern, Switzerland.

Abstract

Hyperuricemia is a common feature in pregnancies compromised by pre-eclampsia, a pregnancy disease characterized by hypertension and proteinuria. The role of uric acid in the pathogenesis of pre-eclampsia remains largely unclear. The aim of this study was to investigate the effect of elevated uric acid serum levels during pregnancy on maternal blood pressure and neonatal outcome using two different murine knockout models. Non-pregnant liver-specific GLUT9 knockout (LG9KO) mice showed elevated uric acid serum concentrations but no hypertensive blood pressure levels. During pregnancy, however, blood pressure levels of these animals increased in the second and third trimester, and circadian blood pressure dipping was severely altered when compared to non-pregnant LG9KO mice. The impact of hyperuricemia on fetal development was investigated using a systemic GLUT9 knockout (G9KO) mouse model. Fetal hyperuricemia caused distinctive renal tissue injuries and, subsequently an impaired neonatal growth pattern. These findings provide strong evidence that hyperuricemia plays a major role in the pathogenesis of hypertensive pregnancy disorders such as pre-eclampsia. These novel insights may enable the development of preventive and therapeutic strategies for hyperuricemia-related diseases.

Keywords: glucose transporter 9; hyperuricemia; knockout model; preeclampsia; uric acid.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Blood Pressure
Female
Humans
Hypertension* / complications
Hyperuricemia*
Mice
Phenotype
Pre-Eclampsia* / genetics
Pregnancy
Pregnancy Complications*
Uric Acid

Substances

Uric Acid

Grants and funding

The study was conducted within the framework of the National Centre of Competence in Research (NCCR) “TransCure—From Transport Physiology to Identification of Therapeutic Targets” (https://www.nccr-transcure.ch/), funded by the Swiss National Science Foundation.