The contribution of placental oxidative stress to early pregnancy failure.
In cases of miscarriage, onset of the maternal blood flow to the placenta is precocious and disorganized compared with this event in normal pregnancy. We sought to determine whether this difference is associated with excessive levels of oxidative damage and stress in the placental tissues. Morphological and immunohistochemical markers of cellular stress and damage, including expression of heat shock protein 70, formation of N-Tyr residues, and lipid peroxidation, were increased in tissues obtained from missed miscarriages compared with controls. The effect was greatest in those pregnancies of shorter than 77 days' duration and with evidence of recent fetal demise. It was associated with increased apoptosis and decreased numbers of mitotic cells, indicating that oxidative stress overwhelms cellular antioxidant defense systems. No differences were observed between miscarriages with normal and abnormal karyotypes. The spectrum of villous changes occurring after fetal demise indicates that the duration of placental retention in utero after fetal demise is a critical determinant of villous histology. The causes of many miscarriages remain unclear; however, our findings indicate that placental oxidative stress with resultant damage to the syncytiotrophoblast, secondary to early onset of the maternal circulation, may provide a final common mechanism.
Hempstock
Joanne
J
Department of Anatomy, Cambridge University, UK.
Jauniaux
Eric
E
Greenwold
Natalie
N
Burton
Graham J
GJ
D000022:Abortion, Spontaneous / Q000209:etiology*; D005260:Female; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D015227:Lipid Peroxidation / Q000502:physiology; D008854:Microscopy, Electron; D018384:Oxidative Stress / Q000502:physiology*; D010920:Placenta / Q000098:blood supply / Q000473:pathology* / Q000648:ultrastructure; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D013997:Time Factors; D014327:Trophoblasts / Q000473:pathology
D018840:HSP70 Heat-Shock Proteins