Elsevier

Human Pathology

Volume 35, Issue 11, November 2004, Pages 1353-1359
Human Pathology

Original contributions
The placental-umbilical unit in sickle cell disease pregnancy: A model for studying in vivo functional adjustments to hypoxia in humans☆

https://doi.org/10.1016/j.humpath.2004.07.003Get rights and content

Abstract

The placental-umbilical unit in sickle cell disease (SCD) pregnancy was used to explore hypoxia in vivo, an important factor in the pathophysiology of this disease. Gross examination and microscopic analysis of the placentas, taken immediately after delivery, indicate good concordance between maturity and term as controls, but higher frequency of vascular injuries such as excess syncytial knots, excess fibrin deposits, congestion and villous necroses. Unexpectedly, neither leukocyte recruitment nor alteration in extraplacental membrane was observed, suggesting the absence of inflammation. Additionally, interleukin (IL)-6 and IL-8 concentrations, measured by enzyme-linked immunosorbent assay (ELISA), were similar in the placental maternal blood from controls and SCD. There were also no significant differences found in IL-6 vein blood concentrations between controls and SCD, IL-8 being not detected. Immunostaining of umbilical vein endothelium in SCD pregnancies showed redistribution of PECAM-1 (CD31), von Willebrand factor (vWF), and P-selectin to the cell surface, controls exhibiting the classical pattern. Staining quantification indicated increases in vWF (+36.2%; P = .006) and vascular endothelial growth factor (VEGF) expression (+96.0%; P = .006) over control, but a reduction in endothelial nitric oxide synthase (eNOS) (−45.5%; P = .029). These results document, for the first time, direct functional adjustments in response to hypoxia in human in vivo. The mechanism for these changes has not been clearly established, but it may reflect increased tolerance to SCD hypoxic conditions and hypoxia in general.

Section snippets

Tissue and blood samples

Twenty fresh human umbilical cords, each 25 cm long, were collected immediately after delivery from pregnant race-matched women (age 18 to 40 years) who delivered in the maternity ward of the University Hospital Center of Guadeloupe. Umbilical vein blood was also collected. In each case, 2 cm of umbilical cord was fixed in formalin and embedded in paraffin or frozen rapidly in liquid nitrogen and stored at −80°C until used, with the remaining cord used for EC isolation (unpublished

Clinical characteristics of the placenta in SCD pregnancy

Although evaluation of pregnancy per se was not the primary objective of the study, macroscopic and microscopic examinations of each placenta were performed. The mean weight was similar in control (440.8 ± 73.1 g) and SCD pregnancies (452.4 ± 89 g), with both groups demonstrating good concordance between maturity and term. However, when compared with controls, more vascular anomalies were detected in SCD pregnancies, mainly in the parenchyma localized between the fetal and maternal surfaces.

Discussion

Despite the physiological and biological mechanisms of pregnancy, we believe that the atypical phenotype observed in SCD is largely due to hypoxia. Our major observations are as follows:

  • 1.

    The hypoxic environment does not induce inflammatory responses in the placental-umbilical unit.

  • 2.

    SCDPvein allows the study of in vivo responses to hypoxia in humans.

  • 3.

    PECAM-1 and VEGF may turn out to be therapeutic targets in SCD induced-hypoxia.

Hypoxic stress often precedes or accompanies tissue inflammation,

Acknowledgements

The authors thank E. Janky and the midwives of the maternity ward of the Hospital Center of Guadeloupe, as well as Dr C. Chicot-Leturdu of the sickle cell center. In memory of C. Berchel, former director of INSERM 516.

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    ☆

    Supported by grants from INSERM, Guadeloupe Region, and the University of Antilles and Guyana.

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