Decreased FGF23 inhibits placental angiogenesis via the ERK1/2-EGR-1 signaling pathway in preeclampsia.

PURPOSE: This study aimed to investigate the expression of fibroblast growth factor 23 (FGF23) in pregnant women with preeclampsia and elucidate its role in promoting placental angiogenesis through the ERK1/2-EGR-1 signaling pathway. METHODS: Serum FGF23 levels were measured by ELISA in healthy pregnant women and patients with preeclampsia during the first, second, and third trimesters of pregnancy. Wound healing, Transwell, and tube formation assays were performed to investigate the effects of FGF23 on cell migration, invasion and tube formation. The expression of vascular endothelial growth factor A (VEGF-A) and its upstream signaling molecules, p-ERK, and EGR-1, in placental tissues was detected by RT-qPCR and western blotting. Additionally, the effect of FGF23 on VEGF-A, p-ERK, and EGR-1 expression was further explored in vitro. RESULTS: Serum FGF23 levels increased with gestational age. During the third trimester, the control group exhibited a more pronounced increase in FGF23 levels than the preeclampsia group. Administering exogenous FGF23 promoted trophoblast cell migration, invasion and enhanced tube formation in vascular endothelial cells. The expression levels of VEGF-A, p-ERK, and EGR-1 in the placental tissues were significantly lower in the preeclampsia group than in the control group. In vitro experiments confirmed that FGF23 up-regulated VEGF-A expression through the p-ERK/EGR-1 signaling pathway. CONCLUSION: The serum level of FGF23 decreased in pregnant women with preeclampsia, inhibiting the ERK1/2-EGR-1 pathway and resulting in decreased expression of VEGF-A, thereby inhibiting placental angiogenesis. This could be a potential mechanism involved in the progression of preeclampsia.

Mechanism of BLIMP1/TRIM66/COX2 in human decidua participates in parturition†.

The mechanism underlying the initiation of parturition remains unclear. Cyclooxygenase 2 and prostaglandins in decidual membrane tissue play an important role in the "parturition cascade." With the advancement of gestation, the expression of the transcriptional suppressor B lymphocyte-induced maturation protein 1 in the decidual membrane gradually decreases. Through chromatin immunoprecipitation sequencing, we found that B lymphocyte-induced maturation protein 1 has a binding site in the distal intergenic of PTGS2(COX2). Tripartite motif-containing protein 66 is a chromatin-binding protein that usually performs transcriptional regulatory functions by "reading" histone modification sites in chromatin. In this study, tripartite motif-containing protein 66 exhibits the same trend of expression as B lymphocyte-induced maturation protein 1 in the decidua during gestation. Moreover, the co-immunoprecipitation assay revealed that tripartite motif-containing protein 66 combined with B lymphocyte-induced maturation protein 1. This finding indicated that tripartite motif-containing protein 66 formed a transcription complex with B lymphocyte-induced maturation protein 1, which coregulated the expression of COX2. In animal experiments, we injected si-Blimp1 adenoviruses (si-Blimp1), Blimp1 overexpression plasmid (Blimp1-OE), and Trim66 overexpression plasmid (Trim66-OE) through the tail vein of mice. The results showed that B lymphocyte-induced maturation protein 1 and tripartite motif-containing protein 66 affected the initiation of parturition in mice. Therefore, the present evidence suggests that B lymphocyte-induced maturation protein 1 and tripartite motif-containing protein 66 partially participate in the initiation of labor, which may provide a new perspective for exploring the mechanism of term labor.

Optical coherence tomography angiography for the characterisation of retinal microvasculature alterations in pregnant patients with anaemia: a nested case‒control study.

AIMS: To characterise retinal microvascular alterations in the eyes of pregnant patients with anaemia (PA) and to compare the alterations with those in healthy controls (HC) using optical coherence tomography angiography (OCTA). METHODS: This nested case‒control study included singleton PA and HC from the Eye Health in Pregnancy Study. Fovea avascular zone (FAZ) metrics, perfusion density (PD) in the superficial capillary plexus, deep capillary plexus and flow deficit (FD) density in the choriocapillaris (CC) were quantified using FIJI software. Linear regressions were conducted to evaluate the differences in OCTA metrics between PA and HC. Subgroup analyses were performed based on comparisons between PA diagnosed in the early or late trimester and HC. RESULTS: In total, 99 eyes of 99 PA and 184 eyes of 184 HC were analysed. PA had a significantly reduced FAZ perimeter (ß coefficient=-0.310, p<0.001), area (ß coefficient=-0.121, p=0.001) and increased circularity (ß coefficient=0.037, p<0.001) compared with HC. Furthermore, higher PD in the central (ß coefficient=0.327, p=0.001) and outer (ß coefficient=0.349, p=0.007) regions were observed in PA. PA diagnosed in the first trimester had more extensive central FD (ß coefficient=4.199, p=0.003) in the CC, indicating impaired perfusion in the CC. CONCLUSION: It was found that anaemia during pregnancy was associated with macular microvascular abnormalities, which differed in PA as pregnancy progressed. The results suggest that quantitative OCTA metrics may be useful for risk evaluation before clinical diagnosis. TRIAL REGISTRATION NUMBERS: 2021KYPJ098 and ChiCTR2100049850.