Intrauterine Inflammation Damages Placental Angiogenesis via Wnt5a-Flt1 Activation

  • F. Xu
  • Z. X. Ren
  • X. M. Zhong
  • Q. Zhang
  • J. Y. Zhang
  • J. YangEmail author


Intrauterine inflammation is the main reason for neonatal adverse outcomes and normal placenta perfusion plays an important role in fetal development. However, whether inflammation will affect placental angiogenesis and the underlying mechanism are still poorly understood. To investigate lipopolysaccharide (LPS)-induced intrauterine inflammation on placenta angiogenesis and Wnt5a-Flt1 expression. LPS-induced intrauterine inflammation rat model was established. Preterm rat outcomes were analyzed and angiogenesis of placenta villi was calculated by immunohistochemistry (IHC) of CD34 staining, and placenta Wnt5a-Flt1 expression was detected by western blot and IHC. Compared to control group, neonatal rats in LPS group showed higher death rate (1.4% vs 10.1%, p < 0.05) and lower birth weight (6.36 ± 0.48 vs 5.70 ± 0.67, p < 0.01); the villi vessel area and mean diameter in the placenta were significantly reduced in the LPS group (total area %, 16.7% ± 0.6% vs 8.7% ± 0.4%, p < 0.01, n = 9; mean diameter (pixel), 15.6 ± 0.5 vs 12.9 ± 0.3, p < 0.01, n = 9). Placenta Wnt5a-Flt1 expression was upregulated significantly (integrated optical density (IOD) in IHC: Wnt5a, 1667 ± 1204 vs 11,076 ± 4046, p < 0.05; Flt1, 2554 ± 466.2 vs 7998 ± 1613, p < 0.05; western blot: Wnt5a, 0.33 ± 0.05 vs 0.96 ± 0.06, p < 0.05; Flt1, 0.36 ± 0.15 vs 1.08 ± 0.08, p < 0.05). Intrauterine inflammation gave rise to offspring death rate and low birth weight; the mechanism might be disordered placental angiogenesis via Wnt5a-Flt1 activation triggered by inflammation.


intrauterine inflammation angiogenesis placenta preterm Wnt5a Flt1 


Availability of Data and Material

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Authors’ Contributions

Xu F, Zhong XM, and Zhang JY performed the experiments; Zhang Q analyzed data and collected the references; and Ren ZX was a major contributor in writing the manuscript. Yang J designed this study and edited the manuscript. All authors read and approved the final manuscript.

Funding Information

This study received financial support from the National Natural Science Foundation of China (81873847) and Guangzhou Technology Program (201707010398, 201804010380).

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflicts of interest.

Ethics Approval


Name of the Ethics Committee That Approved the Study

Guangdong Women and Children Hospital Ethics committee

The Committee’s Reference Number


Consent for Publication

Not applicable.

Supplementary material

10753_2018_936_Fig6_ESM.png (387 kb)
Figure S1

Correlations between Wnt5a-Flt1 protein level (by IHC) and placenta vessel area in control group. N=9. A. No correlation was showed between Wnt5a and Flt1 expression. r=0.065, p=0.86; B. No correlation was showed between Wnt5a expression and placental vessel area. r=0.24, p=0.51. C. No correlation was showed between Flt1 expression and placental vessel area. r=0.35, p=0.36 (PNG 387 kb)

10753_2018_936_MOESM1_ESM.tif (1016 kb)
High resolution image (TIF 1015 kb)


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Neonatology, Guangdong Women and Children HospitalGuang Zhou Medical UniversityGuangzhouChina
  2. 2.Department of Clinical Genetic CenterGuangdong Women and Children HospitalGuangzhouChina
  3. 3.Department of Pathology, Guangdong Women and Children HospitalGuang Zhou Medical UniversityGuangzhouChina

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