Trophoblast syncytialisation necessitates mitochondrial function through estrogen-related receptor-γ activation.
Human pregnancy needs a correct placentation which depends on adequate cytotrophoblast proliferation, differentiation and invasion. In this study, using specific mitochondrial respiratory chain inhibitors, we observed a decrease of hormone production (hCG and leptin) and cell fusion of human primary villous cytotrophoblasts (CT). These results demonstrated that mitochondria are involved in the control of CT differentiation process. Moreover, we also observed a decrease of mitochondrial mass associated with an increase of mitochondrial DNA during CT differentiation. Furthermore, lactate production increased during CT differentiation suggesting that anaerobic metabolism was enhanced in differentiated CTs, and that the role of mitochondria in CT fusion is not only related to its energetic function. Otherwise, the orphan nuclear receptor, estrogen-related receptor γ (ERRγ) is known to orchestrate transcriptional control of energy metabolism genes. In this study, using RNA knockdown and transcriptional activation with DY131 (an ERRγ agonist), we clearly demonstrated that ERRγ promotes hormone production and cell fusion indicating that ERRγ is a key positive transcriptional factor involved in CT differentiation. Finally, we showed that ERRγ promotes mitochondrial biogenesis and function during CT differentiation, and that the role of ERRγ during trophoblast differentiation is mainly mediated by the control of mitochondrial functions.
UPRES-EA 2493, Université de Versailles-St Quentin, UFR des sciences de la santé, 2 avenue de la source de la Bièvre, 78180 Montigny le Bretonneux, France.
Dorothée
D
Poidatz
UPRES-EA 2493, Université de Versailles-St Quentin, UFR des sciences de la santé, 2 avenue de la source de la Bièvre, 78180 Montigny le Bretonneux, France Service de biologie médicale, CHI de Poissy-st-Germain, 78300 Poissy, France.
Esther
E
Dos Santos
UPRES-EA 2493, Université de Versailles-St Quentin, UFR des sciences de la santé, 2 avenue de la source de la Bièvre, 78180 Montigny le Bretonneux, France.
Héloïse
H
Gronier
UPRES-EA 2493, Université de Versailles-St Quentin, UFR des sciences de la santé, 2 avenue de la source de la Bièvre, 78180 Montigny le Bretonneux, France Département de Biologie de la Reproduction, Cytogénétique, Gynécologie et Obstétrique, CHI de Poissy-st-Germain, 78300 Poissy, France.
François
F
Vialard
UPRES-EA 2493, Université de Versailles-St Quentin, UFR des sciences de la santé, 2 avenue de la source de la Bièvre, 78180 Montigny le Bretonneux, France.
Benoit
B
Maury
UPRES-EA 2493, Université de Versailles-St Quentin, UFR des sciences de la santé, 2 avenue de la source de la Bièvre, 78180 Montigny le Bretonneux, France Service de biochimie et génétique moléculaire, Hôpital A. Paré, 92100 Boulogne, France.
Philippe
P
De Mazancourt
UPRES-EA 2493, Université de Versailles-St Quentin, UFR des sciences de la santé, 2 avenue de la source de la Bièvre, 78180 Montigny le Bretonneux, France marie-noelle.dieudonne@uvsq.fr.
Marie-Noëlle
MN
Dieudonné
D000293:Adolescent; D000328:Adult; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D002478:Cells, Cultured; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D008928:Mitochondria / Q000378:metabolism; D010920:Placenta / Q000166:cytology / Q000378:metabolism; D011247:Pregnancy; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism; D014327:Trophoblasts / Q000166:cytology* / Q000378:metabolism; D055815:Young Adult
D011960:Receptors, Estrogen
estrogen-related receptor-γ; mitochondria; placenta; trophoblast differentiation