Elsevier

Human Pathology

Volume 34, Issue 12, December 2003, Pages 1265-1275
Human Pathology

Original contribution
The contribution of placental oxidative stress to early pregnancy failure

https://doi.org/10.1016/j.humpath.2003.08.006Get rights and content

Abstract

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.

Section snippets

Materials and methods

Placental samples were collected with informed written consent from women attending the Early Pregnancy Unit at University College Hospital, London. The University College London Hospitals Committee on the Ethics of Human Research approved the study design. Samples were obtained under low-vacuum aspiration from 65 patients presenting for evacuation of missed miscarriage. The quality and quantity of maternal blood flow to the intervillous space was determined by color-power Doppler ultrasound

Villous morphology

Villi presented a variety of morphological changes within the trophoblast layers and the stromal core. In some samples the fetal capillaries were intact and contained normal biconcave erythrocytes, whereas in others the stromal core was avascular. Intermediate states in which the capillaries displayed discontinuities in their walls and contained fragmented erythrocytes were also observed. A significant negative correlation was found between the volume fraction of the capillaries and the

Discussion

The results demonstrate significant increases in both morphological and immunohistochemical evidence of oxidative syncytial stress and damage in placental tissues from missed miscarriages. The syncytiotrophoblast of early placental villi is highly susceptible to oxidative damage in vitro, as indicated by morphological changes identical to those illustrated here.29 This peculiar susceptibility may reflect the low concentrations of antioxidant enzymes present in this tissue during the first

Acknowledgements

The authors are grateful to Dr. G. Semenza for the gift of a Hif-1α antibody.

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    This study was funded by Tommy’s, The Baby Charity (grant 41). The imaging was performed in the Multi-Imaging Centre of the School of Biological Sciences, Cambridge, UK, which was established with grants from the Wellcome Trust.

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