Universität zu Köln

Nuesken, E., Herrmann, Y., Wohlfarth, M., Goecke, T. W., Appel, S., Schneider, H., Doetsch, J. and Nuesken, K. D. (2015). Strong hypoxia reduces leptin synthesis in purified primary human trophoblasts. Placenta, 36 (4). S. 427 - 433. LONDON: W B SAUNDERS CO LTD. ISSN 1532-3102

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Abstract

Introduction: Oxygen availability severely affects placental function. During placental hypoxia, stabilization of hypoxia inducible factors (HIFs) affects transcription, and leptin gene expression concomitantly increases in vivo and in vitro. However, a causal relationship is uncertain. Methods: We investigated the effect of oxygen availability on HIF-1 alpha (HIF1A) and leptin regulation in primary human trophoblasts isolated from six normal term placentae cultured at 0.1%, 1%, 3%, and 8% oxygen for 6 h, 24 h and 48 h. Gene expressions of leptin (LEP), leptin receptors (LEPR), HIF1A, insulin receptor (INSR) and further genes relevant in hypoxia (VEGFA, EPO, NOS2) or apoptosis (BCL2, BAX, Tp53) were examined. Leptin, HIF1A, INSR, phospho-AKT/AKT (insulin receptor signaling), caspase 3 and cleaved caspase 3 (apoptosis) proteins were measured. Results: A hypoxic reaction with stabilization of HIF1A protein as well as up-regulation of HIF1A and VEGFA gene expressions, but without any hint for apoptosis, was present at 0.1% and 1% oxygen. However, leptin protein concentration (cell supernatants) peaked at 8% oxygen (normoxia) and was significantly reduced at 0.1% oxygen. There was no significant correlation between leptin and HIF1A, neither on the gene nor on the protein level. Discussion: Elevated leptin gene expression in hypoxic placentas may not originate from trophoblasts, but from other placental cells, or from interaction of trophoblasts with other cells. Not only fetal hyperleptinemia, but also fetal hypoleptinemia under hypoxic conditions is conceivable. Strategies to prevent leptin dysregulation during pregnancy should be elucidated to protect the offspring from fetal programming of leptin resistance and adiposity in later life. (C) 2015 Elsevier Ltd. All rights reserved.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Nuesken, E. UNSPECIFIED UNSPECIFIED UNSPECIFIED Herrmann, Y. UNSPECIFIED UNSPECIFIED UNSPECIFIED Wohlfarth, M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Goecke, T. W. UNSPECIFIED UNSPECIFIED UNSPECIFIED Appel, S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Schneider, H. UNSPECIFIED UNSPECIFIED UNSPECIFIED Doetsch, J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Nuesken, K. D. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-408519
DOI:	10.1016/j.placenta.2015.01.191
Journal or Publication Title:	Placenta
Volume:	36
Number:	4
Page Range:	S. 427 - 433
Date:	2015
Publisher:	W B SAUNDERS CO LTD
Place of Publication:	LONDON
ISSN:	1532-3102
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language PLACENTAL LEPTIN; IN-VIVO; EXPRESSION; GENE; INSULIN; CELLS; DIFFERENTIATION; PREECLAMPSIA; PREGNANCIES; HORMONE Multiple languages Developmental Biology; Obstetrics & Gynecology; Reproductive Biology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/40851