Abstract
Anorexia nervosa (AN) is a devastating eating disorder characterized by self-starvation that mainly affects women. Its etiology is unknown, which impedes successful treatment options leading to a limited chance of full recovery. Here, we show that gestation is a vulnerable window that can influence the predisposition to AN. By screening placental microRNA expression of naive and prenatally stressed (PNS) fetuses and assessing vulnerability to activity-based anorexia (ABA), we identify miR-340 as a sexually dimorphic regulator involved in prenatal programming of ABA. PNS caused gene-body hypermethylation of placental miR-340, which is associated with reduced miR-340 expression and increased protein levels of several target transcripts, GR, Cry2 and H3F3b. MiR-340 is linked to the expression of several nutrient transporters both in mice and human placentas. Using placenta-specific lentiviral transgenes and embryo transfer, we demonstrate the key role miR-340 plays in the mechanism involved in early life programming of ABA.
| Original language | English |
|---|---|
| Article number | 1596 |
| Journal | Nature Communications |
| Volume | 9 |
| Issue number | 1 |
| DOIs | |
| State | Published - 1 Dec 2018 |
| Externally published | Yes |
Bibliographical note
Publisher Copyright:© 2018 The Author(s).
Funding
We thank Mr. Sharon Ovadia for his devoted assistance with animal care. We also thank Lisa Tietze for her help with in situ hybridization; Daniela Harbich, Andrea Parl, and Carola Eggert for their help with western blots/stainings; Michael Lüthi for help in human placental RNA isolation and qPCR measurements and Stoyo Karamihalev for help with the graphic images. The authors also wish to express their gratitude to the patients, physicians, and midwives from the Lindenhofgruppe, Bern, for participating in this study. This work was supported by: an FP7 Grant from the European Research Council (260463, A.C.); a research grant from the Israel Science Foundation (1565/15, A. C.); the ERANET Program, supported by the Chief Scientist Office of the Israeli Ministry of Health (3-11389, A.C.); the project was funded by the Federal Ministry of Education and Research under the funding code 01KU1501A (A.C.); research support from Roberto and Renata Ruhman (A.C.); research support from Bruno and Simone Licht; I-CORE Program of the Planning and Budgeting Committee and The Israel Science Foundation (grant no. 1916/12 to A.C.); the Nella and Leon Benoziyo Center for Neurological Diseases (A.C.); the Henry Chanoch Krenter Institute for Biomedical Imaging and Genomics (A.C.); the Perlman Family Foundation, founded by Louis L. and Anita M. Perlman (A.C.); the Adelis Foundation (A.C.); the Marc Besen and the Pratt Foundation and the Irving I. Moskowitz Foundation (A.C.). C.A. was supported by the Swiss National Science Foundation (SNSF) through the National Center of Competence in Research (NCCR) TransCure, University of Bern, Switzerland, and the Swiss National Science Foundation (Grant No. 310030_149958). M.J. was supported by a NARSAD young investigator grant.
| Funders | Funder number |
|---|---|
| Henry Chanoch Krenter Institute for Biomedical Imaging and Genomics | |
| Irving I. Moskowitz Foundation | |
| Marc Besen | |
| Nella and Leon Benoziyo Center for Neurological Diseases | |
| Roberto and Renata Ruhman | 1916/12 |
| Achelis Foundation | |
| National Alliance for Research on Schizophrenia and Depression | |
| Seventh Framework Programme | 260463 |
| Pratt Foundation | |
| nccr – on the move | 310030_149958 |
| Perlman Family Foundation | |
| European Commission | |
| Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung | 149958 |
| Bundesministerium für Bildung und Forschung | 01KU1501A |
| Israel Science Foundation | 1565/15 |
| Ministry of Health, State of Israel | 3-11389 |