Preeclampsia (PE) and intrauterine growth restriction (IUGR) are major obstetric health problems. A well-developed placenta is a key factor for a healthy pregnancy. Cytokines play an important role in human placental development, with a Th1 environment predominant. In PE and IUGR, increased levels of Th2 cytokines have been identified. In PE pregnancies myostatin concentrations in serum and expression in placentae are higher however expression in IUGR pregnancies is unknown. Furthermore the effect of myostatin treatment on in vitro placental cytokine production is also unestablished. In this study myostatin concentrations in plasma of pre-symptomatic women (12-14weeks gestation) who went on to develop IUGR or PE, expression of myostatin protein in IUGR, PE and PE with IUGR in placental tissues and interleukin (IL) 8, Interferon gamma (IFN-γ) and IL-4 concentrations in the media of first trimester placental explant cultures maintained at 1%, 3% and 21% Oxygen ± myostatin treatment (1μg/ml) was evaluated.
Myostatin concentrations obtained by ELISA in pre-symptomatic PE plasma were significantly elevated compared to normal (p = 0.03) and pre-symptomatic IUGR plasma (p = 0.04). Placental expression (obtained by Western blot) of the myostatin dimer and precursor (p < 0.05) forms were significantly higher in IUGR, PE and PE-IUGR compared to gestational age matched placentae. Bio-Plex ELISA measurements of placental explant media identified significantly decreased (p < 0.005) concentrations of interleukin (IL) 8 and Interferon gamma (IFN-γ); however IL-4 concentrations were significantly increased (p < 0.005) following myostatin treatment.
Myostatin concentration and expression is altered in pregnancies complicated with IUGR and PE. Myostatin may act in the placenta by modulating cytokine production, as myostatin treatment decreased (pro-inflammatory) IL-8 and IFN-γ cytokines whilst increasing (anti-inflammatory) IL-4 cytokine production. Potentially, myostatin could assist in the switch from a Th1 to a Th2 rich environment (a switch aberrant in complicated pregnancies).