In vitro exopure to environmental doses of BPA, MEHP and PCBs results in few transcriptions alterations in the fetal sheep ovary - Archive ouverte HAL Accéder directement au contenu
Communication Dans Un Congrès Biology of Reproduction Année : 2013

In vitro exopure to environmental doses of BPA, MEHP and PCBs results in few transcriptions alterations in the fetal sheep ovary

Résumé

Prophase I meiosis and follicle formation are two crucial events of the ovarian development, determining for the future female fertility. Disruption of these initial steps of folliculogenesis results in incomplete sexual development and may contribute to gonadal dysgenesis, infertility or ovarian cancer. Several environmental chemicals are known to affect these developmental processes in rodents following in utero exposure or in vitro culture. However, some mechanisms governing these processes differ between species and reproductive toxicity studies in rodent models correlate poorly with the human. For this reason, sheep are an alternative animal model with many relevant similarities to human ovarian development and to human toxicokinetics. The use of low doses of environmental pollutants close to those found in human biological fluids is crucial in order to mimic the real-life exposure conditions of human gonads. Our aims were: (i) to develop a long-term in vitro ovary organotypic culture allowing both meiosis initiation/progress and follicle morphogenesis/differentiation, and (ii) to evaluate the effects of MEHP (10-6M and 10-8M), PCB 101-118 (10 6M; 10 7M), MEHP + PCB101-118 and BPA (3.10-5M; 3.10-7M), on folliculogenesis and ovary gene expression by microarray analysis. Foetal ovaries were collected at 48dpc, 90dpc and 110dpc then cultured for 21 days in presence of growth/differentiation factors. After each period of culture, per each condition, ovarian fragments were split between histological examination and transcriptome analysis. We have established a foetal ovary culture system in sheep, able to: (i) initiate and maintain meiosis in oogonia, (ii) allow follicle transition and differentiation. Using this culture system, we have shown that in vitro exposure to environmental doses of MEHP and PCB 101-118, produced very few alterations in the sheep foetal ovary transcriptome. MEHP + PCB101-118 and BPA (3.10-7M) exposure at low doses induced less than 10 transcripts differentially expressed at any developmental stage. The dysregulated transcripts were specific for each stage of ovarian development. In contrast, BPA (3.10-5M) exposure resulted in alteration of a large number of transcripts, especially during prophase I meiosis. In conclusion, while BPA (3.10-5M) exposure induced more in vitro changes to foetal ovarian transcripts that other pollutants tested, none at environmental doses (10-7M and 10-8M) produced significant alterations both in transcriptome and ovarian morphology. This research was supported by EU grant (FP7; REEF #212885).
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Dates et versions

hal-01189826 , version 1 (01-09-2015)

Identifiants

  • HAL Id : hal-01189826 , version 1
  • PRODINRA : 226532

Citer

Corinne Cotinot, Béatrice Mandon-Pepin, Benoît Loup, Maria R Amezaga, Richard G Lea, et al.. In vitro exopure to environmental doses of BPA, MEHP and PCBs results in few transcriptions alterations in the fetal sheep ovary. SSR 46. Annual Meeting, Reproductive Health : Nano to Global Program, Jul 2013, Montréal, Canada. ⟨hal-01189826⟩
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