Dataset Information

Toxicogenomics analysis of placenta samples from mice exposed to different doses of BPA

ABSTRACT: Bisphenol A (BPA) is a widespread Endocrine Disrupter mainly used in food contact plastics. Several evidences support BPA adverse effects, especially on susceptible groups such as pregnant women. The present study considered placental development - relevant for pregnancy outcomes and fetal nutrition/programming - as a potential target of BPA. Pregnant CD-1 mice were administered per os with vehicle, 0.5 (BPA05) or 50 mg/kg (BPA50) body weight (bw)/die of BPA, from gestational day (GD) 1 to GD11. At GD12, BPA50 induced significant degeneration and necrosis of giant cells, increased vacuolization in the junctional zone in absence of glycogen accumulation and reduction of the spongiotrophoblast layer. BPA05 induced a significant nuclear accumulation of β-catenin in trophoblasts of the labyrinthine and spongiotrophoblast layers, supporting an activation of the Wnt/β-catenin pathway. Transcriptomic analysis indicated a BPA05 promotion and a BPA50 inhibition of blood vessels development and branching supported by the morphological observation of decreased and increased total vessels area in the labyrinth layers upon BPA05 and BPA50 treatments, respectively, with BPA50 also inducing a decrease in vessels number. These mechanisms involve, respectively, CREB and Wnt/β-catenin pathways for BPA05 and AhR/ARNT pathway for BPA50, as deducted by the transcription factor binding analysis. These results show that BPA differently affects mouse placental development depending on the dose level. In particular, the 0.5 mg/kw bw, in the range of dose level used to set the Tolerable Daily Intake, may elicit not negligible alterations whose relevance for human health has to be carefully evaluated.

ORGANISM(S): Mus musculus

PROVIDER: GSE63852 | GEO | 2014/12/15

SECONDARY ACCESSION(S): PRJNA269258

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:ABSTRACT:Pregnancy requires a higher functional beta cell mass and this is associated with profound changes in the gene expression profile of pancreatic islets. Taking Tph1 as a sensitive marker for pregnancy-related islet mRNA expression in female mice, we previously identified prolactin receptors and placental lactogen as key signalling molecules. Since beta cells from male mice also express prolactin receptors, the question arose whether male and female islets have the same phenotypic resilience at the mRNA level during pregnancy. We addressed this question in vitro, by using islet tissue culture with placental lactogen and in vivo, by transplanting male or female islets into female acceptor mice. Additionally, the islet mRNA expression of pregnant prolactin receptor deficient mice was compared with that of their pregnant wild-type littermates. When cultured with placental lactogen, or transplanted in female recipients that became pregnant (day 12.5), male islets induced the ‘islet pregnancy gene signature’, which we defined as the 12 highest induced genes in non-transplanted female islets at day 12.5 of pregnancy. In addition, serotonin immunoreactivity was also induced in these male transplanted islets at day 12.5 of pregnancy. In order to investigate the importance of prolactin receptors in these mRNA changes we used a prolactin receptor deficient mouse model. For the 12 genes of the signature, which are highly induced in control pregnant mice, no significant induction of mRNA transcripts was found at day 9.5 of pregnancy. Together, our results support the key role of placental lactogen as a circulating factor that can trigger the pregnancy mRNA profile in male and female beta cells. The data obtained from the normal islets of pregnant mice (day12.5) was already described in Schraenen et al. 2010 (PMID: 20886204 and PMID: 20938637). Islets and islet grafts were isolated from non-prengant and pregnant mice for RNA extraction and hybridization on Affymetrix microarrays. For every condition, at least 3 biological replicates were used.

Dataset Information

Toxicogenomics analysis of placenta samples from mice exposed to different doses of BPA

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets