High-fat, high-carbohydrate diet-induced prediabetes preconception in Sprague-Dawley rats as a risk factor for the development of preeclampsia: assessing changes in placental metabolic insults

Asiphaphola Ludidi; Anelisiwe Siboto; Ayanda Nkosi; Nombuso Duduzile Xulu; Andile Khathi; Ntethelelo Hopewell Sibiya; Phikelelani Siphosethu Ngubane

doi:10.3389/fnut.2023.1241785

High-fat, high-carbohydrate diet-induced prediabetes preconception in Sprague-Dawley rats as a risk factor for the development of preeclampsia: assessing changes in placental metabolic insults

Front Nutr. 2023 Oct 23:10:1241785. doi: 10.3389/fnut.2023.1241785. eCollection 2023.

Authors

Asiphaphola Ludidi¹, Anelisiwe Siboto¹, Ayanda Nkosi¹, Nombuso Duduzile Xulu¹, Andile Khathi¹, Ntethelelo Hopewell Sibiya², Phikelelani Siphosethu Ngubane¹

Affiliations

¹ School of Laboratory Medicine and Medical Sciences, College of Health Sciences, University of KwaZulu-Natal, Durban, South Africa.
² Division of Pharmacy, Rhodes University, Makhanda, South Africa.

Abstract

Introduction: Hyperglycemia preconception deranges the establishment of a functional placenta; however, the risk of developing preeclampsia (PE) in prediabetic patients remains obscure. The aim was to assess abnormal placental changes as a risk factor for the development of PE in high-fat, high-carbohydrate (HFHC) diet-induced prediabetic (PD) rats.

Methods: HFHC diet-induced female prediabetic Sprague-Dawley rats were mated, and blood glucose concentrations, mean arterial pressure (MAP), and body weights were monitored on gestational days (GNDs) 0, 9, and 18. On GND 18, animals were euthanized. Blood and placentas were collected for biochemical analysis.

Results: Prediabetic rats showed significantly increased blood glucose concentration, proinflammatory cytokines, MAP, placental weight, and fetoplacental ratio compared with non-prediabetic (NPD) rats. Prediabetic rats showed significantly decreased placental vascular endothelial growth factor receptor 1 (VEGFR1) and placental growth factor (PLGF) and plasma nitric oxide (NO) compared with NPD.

Discussion: Prediabetes may have promoted endothelial dysfunction in the placenta and hypoxia, thus reducing PLGF and VEGFR1, which may have promoted proinflammation, endothelial dysfunction associated with NO decline, and hypertension, which is also observed in preeclamptic patients. Prediabetes may have promoted lipogenesis in placentas and fetuses that may have induced macrosomia and IUGR, also observed in preeclamptic patients. The findings from this study highlight the need for screening and monitoring of prediabetes during pregnancy to reduce the risk of developing preeclampsia.

Keywords: diet; hyperglycemia; inflammation; placenta; prediabetes; preeclampsia.

Grants and funding

The current study was partly funded by the National Research Foundation (NRF) South Africa under the grant number 106613 (https://nrfsubmission.nrf.ac.za/) and the University of KwaZulu-Natal, Research Division (https://ukzn.ac.za/). The funders had no role in the study design, data collection and analysis, and preparation of the manuscript or decision to publish.