Placenta, Environment and Programming of PhenotypeS (PEPPS)

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Placenta, Environment and Programming of PhenotypeS (PEPPS)

Placenta, Environment and Programming of PhenotypeS (PEPPS)

Team leader: Anne Couturier-Tarrade (anne.couturier-tarrade@inrae.fr )

The PEPPS team includes staff from INRAE research departments "Human Nutrition and Food Safety (AlimH)"and "Animal Physiology and Farming (PhASE)" and from the National Veterinary School of Alfort (ENVA). This team, composed of 10 permanent staff members, has expertise in placental and animal physiology, medical imaging, histology, morphometry, lipidology, endocrinology and cellular and molecular biology. In addition, our team develops original approaches in gestation microscopy and imaging.

Team composition: Pascale Chavatte-Palmer (DR2), Andrew Ponter (Prof ENVA), Bénédicte Grimard (Prof ENVA), Anne Couturier-Tarrade (CRCN), Delphine Rousseau-Ralliard (CRCN), María-José Flores Sanabria (CRCN),  Michèle Dahirel (AI), Audrey Prézelin (AI), Emilie Derisoud (PhD student) and internship students (masters, technology institutes...)

Our objectives

To understand and modulate adaptations of placental function in response to the environment, being at the origin of changes in the post-natal phenotype.

Our group studies the role of the placenta on the establishment of fetal, post-natal and intergenerational phenotypes in relation to peri-conceptional and/or gestational disturbances of the maternal environment (nutrition, metabolic status, pollution, nanoparticles, food contaminants). Depending on the type of disturbance, the objective is to identify the window(s) of vulnerability and to understand the adaptive phenomena, in order to propose lifestyle or dietary recommendations for the mother, but also to determine whether placental biomarkers can be used to identify and predict the long-term phenotype of the offspring.

General topic

Intrauterine life imposes specific constraints on the embryo, and subsequently on the fetus, that affect the expression of its genetic potential. As a result, the uterine environment - reflecting various environmental factors, such as the mother's nutrition, embryonic manipulations or the biotic and abiotic stresses the mother has undergone - will affect the development, physiological capacities and health of the offspring up to adulthood. The observation of these effects in humans and then in animals has led to the emergence of the concept of the Developmental Origins of Health and Disease (DOHaD). This concept is based on the existence of a memory of the factors presents in early environment, whose molecular basis is the apposition of epigenetic marks that will regulate genome expression. The regulation of gene expression leads to structural and functional changes in tissues during development that, in adults, will be at the origin of individual variability of the phenotype and adaptation to new environmental stimuli. They are also capable of inducing predisposition or resistance to non-communicable diseases.

The placenta is a complex organ, associated with viviparity. It is formed after the attachment, or implantation, of the embryo to the uterine mucosa and derives from complex cellular and molecular interactions between uterine and embryonic tissues. In mammals, there are various forms of placentation but this organ has the same role in all species, essentially ensuring nutritional exchanges, endocrine and immunological functions between the mother and the fetus.

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Current or emerging scientific themes

  • Effects of maternal exposure, either by inhalation and/or oral route, to micro- and nanoparticles (diesel exhaust particles, metallic particles, food contaminants) on placental function and intrauterine and postnatal health of offspring up to the second generation (rabbit and mouse).
  • Impact of maternal conditions in the horse (nutrition, age, parity, metabolism, lactation concomitant with breeding) on the embryo quality, uterine environment, placental function and the metabolic and osteoarticular health of the foal. Strategies for mitigating these effects on the foal by modifying breeding conditions in the postnatal period are also evaluated.
  • Impact of parental obesity or hyperlipidic diet on placental function and health of offspring (human or animal models: rabbit or rat) and development of strategies to mitigate these effects by dietary supplementation (in rabbits) or bariatric surgery (in rats, in collaboration).
  • Development of cellular trophoblast models to evaluate the capture and passage of low-dose or mixed food contaminants on the placental barrier, their potential effects on placental function (hormonal production, nutrient exchange, cell fusion) or their genotoxic effects, as well as the mechanisms involved (human and rabbit trophoblast models).

Current and emerging work

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Expertise

Animal models:

  • Biomedical models: rabbit, mouse and sheep (rat in collaboration)
  • Livestock models: equine and ovine (pig, cattle, and goat in collaboration)

Disciplinary and technical skills:

  • Physiological explorations:
    • Placental function and fetal development  follow-up (by ultrasound and 3D reconstruction)
    • Glucose metabolism (IVGTT, OGTT, FSIVGTT, euglycemic hyperinsulinemic clamps)
    • Cardiovascular function (blood pressure, heart rate, implanted telemetry)
  • Animal handling: gavage, inhalation exposure, reproduction, /dissection of embryos/feto-placental units, collection of organs and biological fluids
  • Surgery: oocyte puncture, embryo transfer/collection, endoscopy/coelioscopy, interventions on the urogenital sphere, insertion of telemetric probes
  • In vivo imaging: ultrasound-Doppler 2D and 3D GE, Visualsonics micro-ultrasound, Cellvizio, osteodensitometry, iDXA GE  (MIMA2 infrastructure: https://www6.jouy.inrae.fr/mima2 )
  • Histology: classical histology (from paraffin or cryo sections), stereology, immuno-histo-chemistry
  • Ultrastructure: MET, MEB
  • Molecular function through Gene Expression: RT-qPCR, transcriptome analysis by RNAseq or microarray in collaboration)
  • Lipidology: fatty acid profiles by gas chromatography, using Varian 3900 GC-FID with SSL injection + Galaxie sofware and ThermoFisher 1310 GC-FID with SSL-PTV injections + Chromeleon sofware
  • Omics: Metabolomic, lipidomic and proteomic analyses in collaboration
  • Cell biology: cultures of rabbit trophoblastic stem cells and human cell lines
  • Biochemistry: endocrinology by Alphalisa and Elisa, clinical biochemistry

Experimental units and facilities used by the team:

The experimental programs are conducted in close interaction with the experimental units and facilities of INRAE SAAJ (rabbits and sheeps) and IERP (mice and rats), and with the experimental units of IFCE in Chamberet and at the Haras du Pin (for horses), that take care of the animals used by the team. Most of our programs use the resources and skills of the Ile-de-France - Jouy-en-Josas - Antony center :

  • MIMA2 in vivo and in vitro imaging platforms
  • Animal Surgery and Medical Imaging Platform (CIMA) of the MIMA2 platform
  • Transcriptomics and Histology Platforms of the @Bridge Platform

Funding

  • Effects of the maternal environment (micro- and nanoparticles, endocrine disruptors) on offspring
    • Programs in progress: ANSES ENORPREG, ANR EarlyNanoPathoLung, ANR FEDEXPO, Next-PlasTOX by INRAE AlimH funding, ANR PERMALI
    • Programs completed in 2017-2018: ANR EPAPP, ANSES BRAINAIRPOLL and ERC E-DOHAD
  • Impact of maternal and postnatal conditions in horses :
    • Programs in progress: IFCE EPAJ, IFCE FRAGMALIM and FRAGMALIM MARKER-OC
  • Strategies for mitigating and correcting the negative effects of the maternal environment during gestation
    • Program completed in 2017-2018: IFCE ARGIFOAL
  • Development of cellular trophoblast models
    • Internal financing INRAE AlimH (IntTropTox)

Partners

Regional

  • INRAE : GABI, PNCA, MICALIS
  • INSERM 1139 (Paris)
  • IMRB U955 (Créteil)
  • Small Animal Imaging Platform PIPA, Cochin Hospital, Paris
  • Trousseau Hospital (Pediatrics), Hospital Tenon (Biology of Reproduction), HEGP (Biochemistry) (Paris), Foch Hospital (transplantation)
  • PremUp Fundation

National

  • INRAE GenPhyse (Toulouse)
  • IFCE (Chamberet and Le Haras du Pin)
  • ANSES (Fougères)
  • IMRB-U955 (Créteil)
  • INSERM, INRA, INRS, Lorraine University and maternity (Nancy)
  • INSERM U292 (Grenoble)
  • UMR 7263 IMBE (Marseille)
  • Institute of Integrative Biology of the Cell (I2BC) (Gif sur Yvette)
  • Platform Génotoul-Metatoul (Toulouse)

International

  • European institutions: Veterinary School of Liège (Belgique), ETH, Zürich and EMPA (Suisse), RIVM, Bilthoven (Pays-Bas), HBRU (Luxembourg) and National Research Institute of the Working Environment (Danemark)
  • United States of America : Texas A&M

Affiliations

  • COST action Cellfit (CA 16119), (http://cost-cellfit.eu/), Pascale Chavatte-Palmer : MC member and Anne Couturier-Tarrade (MC member substitute)
  • International Embryo Technology Society (IETS, http://www.iets.org) - Pascale Chavatte-Palmer president
  • International Federation of Placenta Associations IFPA (http://www.ifpafederation.org)- Pascale Chavatte-Palmer is in the steering committee
  • European Placenta Group (europeanplacenta.com ) - Pascale Chavatte-Palmer is chairwoman
  • rench society of DOHaD, SF-DOHaD (http://www.sf-dohad.fr) – Pascale Chavatte-Palmer founding member, Anne Couturier-Tarrade member of the board
  • Société Française de Nutrition (http://sf-nutrition.org/) – Delphine Rousseau-Ralliard, member of the Board of Directors
  • Groupe Lipid and Nutrition - Delphine Rousseau-Ralliard, member
  • CELPHEDIA infrastructure network (http://www.celphedia.eu/) – Delphine Rousseau-Ralliard, member of the working group WP4.1 rodent Phenotyping
  • Académie Vétérinaire de France (https://academie-veterinaire-defrance.org) – Pascale Chavatte-Palmer, corresponding member

Publications 2014-2020

Modification date : 08 February 2024 | Publication date : 12 April 2016 | Redactor : Annie P.