The placenta is a transient organ consisting of underlying cytotrophoblasts (CT) which fuse to form the syncytiotrophoblast (ST). During this transformation, the associated mitochondria undergo substantial morphologic alterations. Mitochondria are dynamic organelles which maintain homeostatic balance of ATP, with ST mitochondria integral for the production of progesterone in the placenta and therefore maintenance of the pregnancy. As such, mitochondrial dysfunction may contribute to placental dysfunction, contributing to the pathophysiology of gestational disorders such as gestational diabetes mellitus (GDM). This study examined the bioenergetic and steroidogenic capacity of mitochondria from CT and ST in control and GDM placenta to investigate the role of mitochondria in the development and progression of GDM.
Villous placental tissue was collected from GDM (n=7) and matched control (n=7) pregnancies. Mitochondrial respiration was measure in an O2K oxygraph (Oroboros). ATP production was quantified by flourometric assay. Progesterone was analysed via ELISA.
In healthy control placentae, respiration and ATP production was higher and in CT mitochondria when compared to ST mitochondria (P=0.0202, P=0.0016). Whereas progesterone production was higher in mitochondria from ST compared to CT (P<0.0001). GDM mitochondria, respired lower in both CT and ST compared to control (P=0.0082). Similarly, mitochondrial ATP production was lower in GDM CT (P=0.0024), however greater in ST than control (P=0.0055). Progesterone was increased in GDM (P=0.0026) compared to controls, with ST mitochondria higher than ST controls (P=0.0118).
Results show decreased mitochondrial respiration in GDM, indicating a level of mitochondrial dysfunction in CT and ST. The excess production of ATP by GDM ST mitochondria appears to be for steroidogenesis, with a significant increase in progesterone observed in ST mitochondria, and GDM on the whole, when compared to controls. Progesterone has previously been shown to increase insulin resistance; our research suggests that ST dysfunction and overproduction of progesterone is associated with GDM.