Fetal growth retardation and lack of hypotaurine in ezrin knockout mice

Tomohiro Nishimura, Kei Higuchi, Yoshimichi Sai, Yuki Sugita, Yuko Yoshida, Masatoshi Tomi, Masami Wada, Tomohiko Wakayama, Atsushi Tamura, Sachiko Tsukita, Tomoyoshi Soga, Emi Nakashima

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Ezrin is a membrane-associated cytoplasmic protein that serves to link cell-membrane proteins with the actin-based cytoskeleton, and also plays a role in regulation of the functional activities of some transmembrane proteins. It is expressed in placental trophoblasts. We hypothesized that placental ezrin is involved in the supply of nutrients from mother to fetus, thereby influencing fetal growth. The aim of this study was firstly to clarify the effect of ezrin on fetal growth and secondly to determine whether knockout of ezrin is associated with decreased concentrations of serum and placental nutrients. Ezrin knockout mice (Ez<sup>-/-</sup>) were confirmed to exhibit fetal growth retardation. Metabolome analysis of fetal serum and placental extract of ezrin knockout mice by means of capillary electrophoresis-time-of-flight mass spectrometry revealed a markedly decreased concentration of hypotaurine, a precursor of taurine. However, placental levels of cysteine and cysteine sulfinic acid (precursors of hypotaurine) and taurine were not affected. Lack of hypotaurine in Ez<sup>-/-</sup> mice was confirmed by liquid chromatography with tandem mass spectrometry. Administration of hypotaurine to heterogenous dams significantly decreased the placenta-to-maternal plasma ratio of hypotaurine in wild-type fetuses but only slightly decreased it in ezrin knockout fetuses, indicating that the uptake of hypotaurine from mother to placenta is saturable and that disruption of ezrin impairs the uptake of hypotaurine by placental trophoblasts. These results indicate that ezrin is required for uptake of hypotaurine from maternal serum by placental trophoblasts, and plays an important role in fetal growth.

Original languageEnglish
Article numbere105423
JournalPLoS One
Volume9
Issue number8
DOIs
Publication statusPublished - 2014 Aug 21

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Fetal Growth Retardation
fetal development
Knockout Mice
growth retardation
trophoblast
fetus
taurine
mice
uptake mechanisms
placenta
cysteine
Trophoblasts
Fetal Development
transmembrane proteins
capillary electrophoresis
nutrients
metabolomics
Fetus
cytoskeleton
Taurine

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Fetal growth retardation and lack of hypotaurine in ezrin knockout mice. / Nishimura, Tomohiro; Higuchi, Kei; Sai, Yoshimichi; Sugita, Yuki; Yoshida, Yuko; Tomi, Masatoshi; Wada, Masami; Wakayama, Tomohiko; Tamura, Atsushi; Tsukita, Sachiko; Soga, Tomoyoshi; Nakashima, Emi.

In: PLoS One, Vol. 9, No. 8, e105423, 21.08.2014.

Research output: Contribution to journalArticle

Nishimura, T, Higuchi, K, Sai, Y, Sugita, Y, Yoshida, Y, Tomi, M, Wada, M, Wakayama, T, Tamura, A, Tsukita, S, Soga, T & Nakashima, E 2014, 'Fetal growth retardation and lack of hypotaurine in ezrin knockout mice', PLoS One, vol. 9, no. 8, e105423. https://doi.org/10.1371/journal.pone.0105423
Nishimura, Tomohiro ; Higuchi, Kei ; Sai, Yoshimichi ; Sugita, Yuki ; Yoshida, Yuko ; Tomi, Masatoshi ; Wada, Masami ; Wakayama, Tomohiko ; Tamura, Atsushi ; Tsukita, Sachiko ; Soga, Tomoyoshi ; Nakashima, Emi. / Fetal growth retardation and lack of hypotaurine in ezrin knockout mice. In: PLoS One. 2014 ; Vol. 9, No. 8.
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