Fetal growth retardation and lack of hypotaurine in ezrin knockout mice.
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...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2014-01-01
|
| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4140781?pdf=render |
| _version_ | 1819038151477297152 |
|---|---|
| author | Tomohiro Nishimura Kei Higuchi Yoshimichi Sai Yuki Sugita Yuko Yoshida Masatoshi Tomi Masami Wada Tomohiko Wakayama Atsushi Tamura Sachiko Tsukita Tomoyoshi Soga Emi Nakashima |
| author_facet | Tomohiro Nishimura Kei Higuchi Yoshimichi Sai Yuki Sugita Yuko Yoshida Masatoshi Tomi Masami Wada Tomohiko Wakayama Atsushi Tamura Sachiko Tsukita Tomoyoshi Soga Emi Nakashima |
| author_sort | Tomohiro Nishimura |
| collection | DOAJ |
| description | 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(-/-)) 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(-/-) 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. |
| first_indexed | 2024-12-21T08:32:45Z |
| format | Article |
| id | doaj.art-29cf1a09b121421f93e76886c517288f |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-21T08:32:45Z |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-29cf1a09b121421f93e76886c517288f2022-12-21T19:10:08ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0198e10542310.1371/journal.pone.0105423Fetal growth retardation and lack of hypotaurine in ezrin knockout mice.Tomohiro NishimuraKei HiguchiYoshimichi SaiYuki SugitaYuko YoshidaMasatoshi TomiMasami WadaTomohiko WakayamaAtsushi TamuraSachiko TsukitaTomoyoshi SogaEmi NakashimaEzrin 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(-/-)) 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(-/-) 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.http://europepmc.org/articles/PMC4140781?pdf=render |
| spellingShingle | Tomohiro Nishimura Kei Higuchi Yoshimichi Sai Yuki Sugita Yuko Yoshida Masatoshi Tomi Masami Wada Tomohiko Wakayama Atsushi Tamura Sachiko Tsukita Tomoyoshi Soga Emi Nakashima Fetal growth retardation and lack of hypotaurine in ezrin knockout mice. PLoS ONE |
| title | Fetal growth retardation and lack of hypotaurine in ezrin knockout mice. |
| title_full | Fetal growth retardation and lack of hypotaurine in ezrin knockout mice. |
| title_fullStr | Fetal growth retardation and lack of hypotaurine in ezrin knockout mice. |
| title_full_unstemmed | Fetal growth retardation and lack of hypotaurine in ezrin knockout mice. |
| title_short | Fetal growth retardation and lack of hypotaurine in ezrin knockout mice. |
| title_sort | fetal growth retardation and lack of hypotaurine in ezrin knockout mice |
| url | http://europepmc.org/articles/PMC4140781?pdf=render |
| work_keys_str_mv | AT tomohironishimura fetalgrowthretardationandlackofhypotaurineinezrinknockoutmice AT keihiguchi fetalgrowthretardationandlackofhypotaurineinezrinknockoutmice AT yoshimichisai fetalgrowthretardationandlackofhypotaurineinezrinknockoutmice AT yukisugita fetalgrowthretardationandlackofhypotaurineinezrinknockoutmice AT yukoyoshida fetalgrowthretardationandlackofhypotaurineinezrinknockoutmice AT masatoshitomi fetalgrowthretardationandlackofhypotaurineinezrinknockoutmice AT masamiwada fetalgrowthretardationandlackofhypotaurineinezrinknockoutmice AT tomohikowakayama fetalgrowthretardationandlackofhypotaurineinezrinknockoutmice AT atsushitamura fetalgrowthretardationandlackofhypotaurineinezrinknockoutmice AT sachikotsukita fetalgrowthretardationandlackofhypotaurineinezrinknockoutmice AT tomoyoshisoga fetalgrowthretardationandlackofhypotaurineinezrinknockoutmice AT eminakashima fetalgrowthretardationandlackofhypotaurineinezrinknockoutmice |