Placental and serum levels of human α-Klotho in preeclampsia & intra-uterine growth retardation: A potential sensitive biomarker?

Shehada Sabren, Tadmor Hagar, Nardeen Khateeb, Farber Evgeny, Francis Nakhle Yara, Youri Perlitz, Nakhoul Farid

Research output: Contribution to journalArticlepeer-review

Abstract

Introduction: α-Klotho protein has three isoforms: a transmembrane (mKL), a shed- soluble isoform, and a circulating soluble isoform (sKL). mKL is expressed in the kidney and placenta, while sKL is detectable in blood and urine. It is known that α-Klotho levels fluctuate during pregnancy mainly in women with complications such as preeclampsia (PE) and intra-uterine growth restriction (IUGR). Methods: Forty-nine participants were divided into two groups: healthy and complicated pregnancy (PE, IUGR or both). Tissue samples (2 cm3) from the maternal side, Blood and urine samples were collected during pregnancy and postpartum. Samples were subjected to biochemical (WB), histological (H&E and IHC) staining as well as genetic analysis (qPCR). Results: Blood αKL levels were preserved in both healthy and complicated pregnancies. Significantly lower blood αKL concentrations were found in PE postpartum (PP) compared to levels during pregnancy, and were significantly lower compared with postpartum of a healthy pregnancy. αKL activity was reduced in complicated pregnancies vs. healthy pregnancies. Placen tal mKL levels (ELISA) and expression (WB) were lowered in complicated pregnancies compared with the healthy pregnancies group. Additionally, we found a significant decline in the expression of mKL mRNA in PE/IUGR placentas compared with the healthy group. Discussion: Several studies have focused on the involvement of αKL in normal placentation during pregnancy. Our results suggest lower function of sKL in complicated pregnancy compared with a control, and present differences in placental mKL levels as well as tissue and gene expression between healthy and complicated pregnancy. In light of our results, we conclude that complicated pregnancy is associated with in decline in mKL.

Original languageEnglish
Article number101115
JournalPregnancy Hypertension
Volume36
StatePublished - Jun 2024

Bibliographical note

Publisher Copyright:
© 2024 International Society for the Study of Hypertension in Pregnancy

Keywords

  • Healthy pregnancy
  • Intrauterine growth restriction (IUGR)
  • Placenta
  • Preeclampsia (PE)
  • α-Klotho

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