Vitamin D supplementation as a prophylactic therapy in the management of pre-eclampsia: Focus on VEGF, Ki67, oxidative stress markers in correlation to placental ultra structure

Hanan Eissa; Eman Mohamed Abdelsalam; Somaia A Mokbel; Nada H Elhadedy; Rania M Khalil; Amany AbdElfattah Mohamed AbdElfattah; Dalia M Abdel Ghaffar; Eman Mohamad El Nashar; Alshehri Hanan Hassan; Norah Saeed Al-Zahrani; Rashid A Aldahhan; Neimat Abd Elhakam Yassin

doi:10.1016/j.lfs.2025.123605

Vitamin D supplementation as a prophylactic therapy in the management of pre-eclampsia: Focus on VEGF, Ki67, oxidative stress markers in correlation to placental ultra structure

Life Sci. 2025 Apr 5:372:123605. doi: 10.1016/j.lfs.2025.123605. Online ahead of print.

Affiliations

¹ Department of Clinical Pharmacology, Mansoura University, Mansoura, Egypt. Electronic address: Dr_hananpharma@mans.edu.eg.
² Department of Clinical Pharmacology, Mansoura University, Mansoura, Egypt.
³ Department of Clinical Pharmacology, Mansoura University, Mansoura, Egypt. Electronic address: somaia_mokbel@mans.edu.eg.
⁴ Department of Clinical Pathology, Mansoura University, Mansoura, Egypt.
⁵ Department of Biochemistry, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa, Egypt. Electronic address: Rania.khalil@deltauniv.edu.eg.
⁶ Department of Medical Histology & Cell Biology, Faculty of Medicine, Mansoura University, Mansoura, Egypt; Department of Basic Medical Sciences, Faculty of Medicine, King Salman International University, South Sinai, Egypt. Electronic address: Monay_2006@mans.edu.eg.
⁷ Department of Physiology, Faculty of Medicine, Mansoura University, Mansoura, Egypt. Electronic address: Dalia.mr@mans.edu.eg.
⁸ Department of Anatomy, College Medicine, King Khalid University, Abha 62529, Saudi Arabia. Electronic address: enshar@kku.edu.sa.
⁹ Endocrinology and Diabetes Section, Internal Medicine Department, College of Medicine, King Khalid University, Abha 62529, Saudi Arabia. Electronic address: hhsalim@kku.edu.sa.
¹⁰ Department of Clinical Biochemistry, College of Medicine, King Khalid University, Abha 62529, Saudi Arabia. Electronic address: noraelzahrani@kku.edu.sa.
¹¹ Department of Anatomy, College of Medicine, Imam Abdulrahman Bin Faisal University, P.O. Box 2114, Dammam 31451, Saudi Arabia. Electronic address: raaldahhan@iau.edu.sa.
¹² Department of Clinical Pharmacology, Mansoura University, Mansoura, Egypt. Electronic address: dr_neimatpharma@mans.edu.eg.

PMID: 40194761
DOI: 10.1016/j.lfs.2025.123605

Abstract

Background: Pre-eclampsia (PE) is a progressive hypertension condition that manifests in the second or third trimester of pregnancy and causes significant proteinuria. A lack of vitamin D (Vit. D) is linked to different pregnancy problems, including impaired placental development. Vitamin D has been shown to enhance fetal growth and lower the incidence of PE.

Aim of the work: To better understand the pathophysiological mechanisms behind the PE disease and the therapeutic approaches used to manage it, this study examines the role of Vit. D in placental ischemia and its regulatory effects in Nitro L-arginine Methyl Ester (L-NAME) animal model of PE.

Methods: Fifty female rats in the estrus stage were mated with 30 male rats. Thirty female rats were pregnant and divided into three equal groups: control, Preeclampsia group (PE); using L-NAME for induction of PE, and Vit. D group from 7th day then induction by L-NAME at 10th day till end of pregnancy. Mean arterial Bp, proteinuria, oxidative stress markers, histological structure and immunohistochemical expression of Ki67 and VEGF, Morphometric study, and transmission electron microscopy(TEM) were assessed. The results of the current study suggested that, Vit. D supplementation could lower blood pressure, reduce oxidative stress, and restore angiogenic balance through vascular endothelial growth factor (VEGF) and Ki67.

Conclusion: For the first time, we conclude that vitamin D supplementation may not only have direct effects on blood pressure regulation and angiogenic hemostasis but also recover placental function, actually contributing to the prevention or management of PE.

Keywords: Angiogenesis; Oxidative stress; Placental ischemia; Placental ultra structure; Pre-eclampsia; Prophylactic therapy; Vitamin D.