Folate Deficiency Could Restrain Decidual Angiogenesis in Pregnant Mice.

Yanli Li,Xuemei Chen,Rufei Gao,Yingxiong Wang,Junlin He,Yubin Ding,Xinggui Liao,Xueqing Liu,Yanqing Geng

doi:10.3390/nu7085284

Yanli Li, Xuemei Chen + Show 7 more

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https://doi.org/10.3390/nu7085284

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Abstract

The mechanism of birth defects induced by folate deficiency was focused on mainly in fetal development. Little is known about the effect of folate deficiency on the maternal uterus, especially on decidual angiogenesis after implantation which establishes vessel networks to support embryo development. The aim of this study was to investigate the effects of folate deficiency on decidual angiogenesis. Serum folate levels were measured by electrochemiluminescence. The status of decidual angiogenesis was examined by cluster designation 34 (CD34) immunohistochemistry and the expression of angiogenic factors, including vascular endothelial growth factor A (VEGFA), placental growth factor (PLGF), and VEGF receptor 2 (VEGFR2) were also tested. Serum levels of homocysteine (Hcy), follicle stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), progesterone (P4), and estradiol (E2) were detected by Enzyme-linked immunosorbent assay. The folate-deficient mice had a lower folate level and a higher Hcy level. Folate deficiency restrained decidual angiogenesis with significant abnormalities in vascular density and the enlargement and elongation of the vascular sinus. It also showed a reduction in the expressions of VEGFA, VEGFR2, and PLGF. In addition, the serum levels of P4, E2, LH, and PRL were reduced in folate-deficient mice, and the expression of progesterone receptor (PR) and estrogen receptor α (ERα) were abnormal. These results indicated that folate deficiency could impaire decidual angiogenesis and it may be related to the vasculotoxic properties of Hcy and the imbalance of the reproductive hormone.

Highlights

Birth defects or congenital anomalies are one of the major causes of disability in developed and developing countries [1]
The electro-chemiluminescence immunoassay was used to measure the serum folate levels to verify the validity of the pregnant mouse model
Hcy, the intermediate product in folate metabolism and one of the factors influencing the biological functions of the vascular endothelium, serum levels were determined with enzyme-linked immunosorbent assay (ELISA)

Summary

Introduction

Birth defects or congenital anomalies are one of the major causes of disability in developed and developing countries [1]. The March of Dimes estimated that 7.4 million infants are born each year with a serious birth defect. Of these births, 94% occur in middle- and low-income countries [2]. Birth defects are a population health problem affecting the quality of the birth population in China. In high-prevalence areas of China, the prevalence of birth defects was 537.2 per 10,000 births and the first five main birth defects were anencephaly, congenital heart diseases, spina bifida, hydrocephaly, and encephalocele [3]. The causes of birth defects can be grouped into three main categories: (1) genetic,

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