A Role for Adiponectin in Trophoblast Function

Abstract

As the ultimate mediator of fetal growth and well-being, the placenta is inundated with a number of molecular cues from both the maternal and fetal systems. Successful integration of these signals is critical to the ongoing health of the pregnancy, and may have important implications for the future health of both mother and child. Maternal adipose tissue releases a variety of adipokines, whose primary aim is to regulate energy metabolism. Given this, and the importance of this process in the placenta, it follows that adipokines may have profound effects on the trophoblast cells of the placenta. However, the influence of most of these adipokines on the placenta remains poorly understood. We examined the role the adipokine, adiponectin, has on the human placenta using isolated trophoblasts collected from healthy term pregnancies. Treatment of these cells with adiponectin in culture inhibited the production of human chorionic gonadotropin (hCG), placental lactogen and progesterone, all hormones produced by the placenta that play a key role in the continued health and viability of the pregnancy. In addition, adiponectin induced a pro-inflammatory environment in trophoblast cells, with increases in production of both interleukin (IL)-1β and IL-8. We have gone on to show that adiponectin can mediate its actions on trophoblast cells through the adaptor protein APPL1, the signaling molecules mitogen-activated protein kinases (MAPKs), and the epidermal growth factor (EGF) receptor. Finally, we examined the effects of adiponectin on gene expression by term trophoblasts. These data have highlighted a number of additional processes influenced by adiponectin, including insulin-like growth factor bioavailability and cortisol metabolism. The implications for these effects at the maternal-fetal interface are great. From these data, we hypothesize that adiponectin works to maintain the balance between the energy demands of the fetus and the needs of the mother, with specific functions at the placenta that appear to favor the mother. Such a role is increasingly critical as gestation progresses and fetal demands continue to increase. With the continued prevalence of metabolic health diseases, such as obesity, it is especially important to understand the influences hormones such as adiponectin have on the placenta.