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Epigenetically‐induced vascular dysfunction and hypertension by in vitro fertilization; prevention by addition of melatonin to the culture media
Author(s) -
Rexhaj Emrush,
Rimoldi Stefano,
Giacobino Ariane,
Sartori Claudio,
Allemann Yves,
Scherrer Urs
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.874.15
Subject(s) - melatonin , blastocyst , enos , epigenetics , in vitro , in vivo , dna methylation , endocrinology , medicine , andrology , endothelial dysfunction , biology , embryo , gene , microbiology and biotechnology , embryogenesis , nitric oxide , gene expression , genetics , nitric oxide synthase
In vitro fertilization (IVF) induces vascular dysfunction in mice and humans that may be related to an epigenetic mechanism. We speculated that this problem is induced during blastocyst culture. We therefore tested the effects of the addition of melatonin – a pineal gland hormone that acts on epigenetic regulation ‐ to the culture media on DNA‐methylation of genes in vascular tissue and vascular function in vitro and in vivo in 12 weeks‐old IVF mice. We found that addition of melatonin (10 −6 M) to the culture media prevented the dysmethylation of imprinted genes H19 (P=.05, vs. vehicle), Gtl2 (P=.04, vs. vehicle), Peg3 (P<.01, vs. vehicle) and of the eNOS promoter (P=.02, vs. vehicle) in IVF mice. Prevention of vascular DNA dysmethylation in IVF mice by melatonin was accompanied by normalization of the mesentery‐artery responsiveness to acetylcholine in vitro (P<.0001 vs. vehicle) and arterial blood pressure in vivo in vivo (105±4 vs. 109±4 mmHg, X±SD, P=.04 vs. vehicle). Here we show for the first time that IVF induces vascular dysfunction by an epigenetic mechanism that is triggered during blastocyst culture. We speculate that in humans IVF induces vascular dysfunction by a similar mechanism. If so, modification of the culture media may allow to prevent this problem in humans.