Fetal-to-maternal signaling to initiate parturition

Abstract

Multiple processes are capable of activating the onset of parturition; however, the specific contributions of the mother and the fetus to this process are not fully understood. In this issue of the JCI, Gao and colleagues present evidence that steroid receptor coactivators 1 and 2 (SRC-1 and SRC-2) regulate surfactant protein-A (SP-A) and platelet-activating factor (PAF) expression, which increases in the developing fetal lung. WT dams crossed with males deficient for both SRC-1 and SRC-2 had suppressed myometrial inflammation, increased serum progesterone, and delayed parturition, which could be reconciled by injection of either SP-A or PAF into the amnion. Together, the results of this study demonstrate that the fetal lungs produce signals to initiate labor in the mouse. This work underscores the importance of the fetus as a contributor to the onset of murine, and potentially human, parturition.

Figure 1. Mechanism of fetal signaling to initiate parturition.

Late in fetal lung development, the transcriptional regulators SRC-1 and SRC-2, in coordination with NF-κB, TTF-1, and GR, promote SP-A and LPCAT1 expression. SP-A and PAF are released into the amniotic fluid, where they initiate the shuttling of macrophages to the myometrium, resulting in an increase in myometrial NF-κB, leading to an increase in PGF₂α and CAPs. A rise in circulating levels of PGF₂α promotes luteolysis by decreasing StAR expression, leading to a drop in maternal progesterone (P₄) and the onset of parturition.