The Mitochondrial Cholesterol Transporter TSPO—Gatekeeper of Gestational Progesterone Production

Résumé fourni par la source

During pregnancy, progesterone is exclusively produced by the placenta. As in all steroidogenic tissues, the first and rate-limiting step for the biosynthesis of placental progesterone is the import of cholesterol into the mitochondria via specific transporters. Plasma progesterone is 20% lower in pregnant obese women despite increased cholesterol availability suggesting an impairment in cholesterol import mechanisms. We investigated the role of the outer mitochondrial translocator protein (TSPO), the placental analog of StAR, as a potential regulator of placental progesterone production. Study design: Villous fragments of placentas were collected at term scheduled Cesarean delivery of lean and obese women with normal glucose tolerance. Trophoblast cells were isolated and plated for primary culture. In vitro silencing of TSPO was performed by transfecting primary trophoblast cells with siRNA. Progesterone production was measured in lysates of trophoblast cells before and after TSPO silencing. Results and Discussion: TSPO mRNA and protein expression were 2 to 3-fold lower in placentas of obese vs. lean women. TSPO siRNA silencing in trophoblast cells induced a 90% (p<0.001) decrease in TSPO protein expression, with no change in other proximal translocators: the voltage anion dependent channel (VDAC) and the adenine nucleotide translocator (ANT). Progesterone concentration dropped by 85% (p< 0.001) upon TSPO silencing. These results demonstrate that the cholesterol translocator TSPO directly regulates the production of placental progesterone. Together, our data point to mitochondrial dysfunction as a component of progesterone deficiency in obese pregnant women. Disclosure M. Haghiac: None. J. Minium: None. Y. Skomorovska-Prokvolit: None. P. Catalano: None. S. Hauguel de Mouzon: None.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.