TY - JOUR
T1 - Placental miR-340 mediates vulnerability to activity based anorexia in mice
AU - Schroeder, Mariana
AU - Jakovcevski, Mira
AU - Polacheck, Tamar
AU - Drori, Yonat
AU - Luoni, Alessia
AU - Röh, Simone
AU - Zaugg, Jonas
AU - Ben-Dor, Shifra
AU - Albrecht, Christiane
AU - Chen, Alon
N1 - Publisher Copyright:
© 2018 The Author(s).
PY - 2018/4/23
Y1 - 2018/4/23
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85045974963&partnerID=8YFLogxK
U2 - 10.1038/s41467-018-03836-2
DO - 10.1038/s41467-018-03836-2
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C2 - 29686286
AN - SCOPUS:85045974963
SN - 2041-1723
VL - 9
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 1596
ER -