Altered cord serum 25-hydroxyvitamin D signaling and placental inflammation is associated with pre-term birth

Am J Reprod Immunol. 2020 Feb;83(2):e13201. doi: 10.1111/aji.13201. Epub 2019 Nov 17.

Abstract

Problem: Vitamin D is well-known for having anti-inflammatory and immunomodulatory properties. Impaired maternal vitamin D status has been known to increase the risk of adverse pregnancy outcomes like pre-term birth. The present study aims to evaluate the impact of fetal cord serum 25-hydroxyvitamin D-mediated signaling in mediating inflammatory responses in placenta during pre-term birth.

Method of study: For the above purpose, cord serum 25 hydroxyvitamin D 25(OH)D were measured in term (n = 20) and pre-term (n = 20) born babies using ELISA. Vitamin D downstream signaling has also been checked in placenta (VDR, CYP27B1, cathelicidin LL37) along with expression of inflammatory markers (S100A8, HMGB1, TLR2, p-NF-kappaB) using Western blotting and immunohistochemistry. Pearson correlation model was used to do correlation study.

Results: Compared with term born babies (59.31 ± 3.476), decline in cord serum 25(OH)D levels is observed in pre-term born babies (22.26 ± 1.083, P = <0.0001) that showed strong positive correlation with gestational age (r = .9368***) and birthweight (r = .9559***). On the other hand, vitamin D signaling markers were found to be downregulated and inflammatory markers were upregulated in placental tissue of pre-term born babies.

Conclusion: Thus, our study demonstrated that insufficient cord 25(OH)D levels may disturb the homeostasis of inflammation in placenta. Altered cord serum 25(OH)D mediated anti-inflammatory signaling may be acting as trigger signals in modulating inflammatory responses in placenta and eliciting premature activation of spontaneous labor in pre-term birth.

Keywords: anti-inflammatory; placental inflammation; pre-term birth; pregnancy; vitamin D.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 25-Hydroxyvitamin D3 1-alpha-Hydroxylase / biosynthesis
  • 25-Hydroxyvitamin D3 1-alpha-Hydroxylase / genetics
  • Adult
  • Birth Weight
  • Chorionic Villi / metabolism
  • Chorionic Villi / pathology
  • Female
  • Fetal Blood / chemistry*
  • Gestational Age
  • Humans
  • Infant
  • Infant, Premature / blood*
  • Inflammation / blood*
  • Inflammation / pathology
  • Inflammation Mediators / analysis
  • Placenta Diseases / blood*
  • Placenta Diseases / pathology
  • Pregnancy
  • Pregnancy Complications / blood
  • Premature Birth / blood*
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Receptors, Calcitriol / biosynthesis
  • Receptors, Calcitriol / genetics
  • Transcription Factor RelA / blood
  • Vitamin D / analogs & derivatives*
  • Vitamin D / blood
  • Vitamin D Deficiency / blood

Substances

  • Inflammation Mediators
  • RNA, Messenger
  • Receptors, Calcitriol
  • Transcription Factor RelA
  • Vitamin D
  • 25-hydroxyvitamin D
  • 25-Hydroxyvitamin D3 1-alpha-Hydroxylase
  • CYP27B1 protein, human