Stretching, mechanotransduction, and proinflammatory cytokines in the fetal membranes.
In the third trimester of normal pregnancy, the human fetal membranes become increasingly distended and use mechanotransduction and its downstream signaling to remodel and function. Their overdistension either by multifetal pregnancy or by polyhydramnios often leads to preterm birth, but the mechanism is unclear. Stretching of the fetal membranes in vitro upregulates several cytokines and enzymes that can drive collagen degradation, leading to membrane rupture. The sensitivity of this response appears to be specific for different cell types and is likely to result from differential activation of some key transcription factors and cofactors. Few cytokines in the fetal membranes respond to stretch: the most robust of these is pre-B-cell colony-enhancing factor (PBEF). This is constitutively expressed and protects the amnion cells from apoptosis caused by chronic static distension. However, it can also be stimulated by inflammation, infection, and hypoxia and upregulates a number of proinflammatory cytokines, chemokines, and enzymes important in the initiation of parturition. Therefore, it is proposed here that PBEF functions in normal pregnancy to protect the amnion cells as they become increasingly stretched, but if stimulated, it can initiate key events leading to parturition.
Kendal-Wright
Claire E
CE
Developmental and Reproduction Biology, John A. Burns School of Medicine, and the Pacific Biomedical Research Center, University of Hawaii, Honolulu, HI 96813, USA. kendal@pbrc.hawaii.edu
D003094:Collagen / Q000378:metabolism; D016207:Cytokines / Q000276:immunology / Q000378:metabolism*; D005321:Extraembryonic Membranes / Q000201:enzymology / Q000378:metabolism*; D005260:Female; D005322:Premature Rupture of Fetal Membranes / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D007113:Immunity, Innate; D008465:Mechanoreceptors / Q000196:embryology / Q000378:metabolism*; D040542:Mechanotransduction, Cellular; D054409:Nicotinamide Phosphoribosyltransferase / Q000276:immunology / Q000378:metabolism; D036801:Parturition; D006831:Polyhydramnios / Q000378:metabolism / Q000503:physiopathology; D011247:Pregnancy; D011263:Pregnancy Trimester, Third; D012421:Rupture; D013718:Tensile Strength; D015854:Up-Regulation
D016207:Cytokines; D003094:Collagen; D054409:Nicotinamide Phosphoribosyltransferase; C085455:nicotinamide phosphoribosyltransferase, human