Intrauterine Inflammation Damages Placental Angiogenesis via Wnt5a-Flt1 Activation
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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.
KEY WORDSintrauterine 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.
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.
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.
Name of the Ethics Committee That Approved the Study
Guangdong Women and Children Hospital Ethics committee
The Committee’s Reference Number
Consent for Publication
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