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Updated: Jan 22, 2026
The 4-vessel Sampling Approach to Integrative Studies of Human Placental Physiology In Vivo
Published on: August 2, 2017
Immunohistochemical analysis of placental Netrin-1, Netrin-4, and UNC5B in preeclampsia
Deniz Aydın Ceylan1, Cihan Kabukçu2, Yeliz Arman Karakaya3
1Department of Obstetrics and Gynecology, Silifke State Hospital, Mersin, Türkiye; Department of Obstetrics and Gynecology, School of Medicine, Pamukkale University, Denizli, Türkiye.
Introduction:
Preeclampsia (PE) is a hypertensive disorder of pregnancy characterized by impaired placental angiogenesis and an imbalance between pro- and anti-angiogenic factors. Netrin-1, Netrin-4, and their receptor UNC5B are critical modulators of vascular development. This study investigated their immunohistochemical expression in preeclamptic and healthy placentas.
Methods:
Placental tissues from 96 women with PE and 71 healthy term controls were analyzed. Immunohistochemistry was performed on tissue microarrays, and immunoreactivity scores (IRS) were calculated based on staining intensity and extent. Expression profiles were compared between groups and across disease severity and gestational age subgroups.
Results:
Netrin-1 expression was significantly reduced in preeclamptic placentas compared with controls (mean IRS 3.46 ± 2.57 vs. 6.77 ± 3.17; p < 0.0001), whereas Netrin-4 and UNC5B were markedly upregulated (Netrin-4: 8.60 ± 3.22 vs. 1.92 ± 1.59; UNC5B: 4.75 ± 1.95 vs. 3.49 ± 1.30; all p < 0.0001). Netrin-1 remained consistently decreased across severity subgroups, while Netrin-4 expression was significantly higher in severe versus non-severe PE (p = 0.002). Expression levels did not differ between early- and late-onset PE. Correlation analysis showed a negative association between Netrin-1 and Netrin-4 (r = -0.425) and a positive correlation between Netrin-4 and UNC5B (r = 0.439) (both p < 0.0001).
Conclusion:
PE is associated with a coordinated shift in the placental Netrin signaling axis, characterized by downregulation of the pro-angiogenic Netrin-1 and upregulation of the anti-angiogenic ligand Netrin-4 and receptor UNC5B. These findings suggest that Netrin-mediated angiogenic imbalance may play a key role in the pathogenesis of preeclampsia.
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