Decidual stromal cell regulation of trophoblast in first trimester pregnancies with normal and impaired spiral artery remodelling

Abstract Background: Downstream remodeling of the spiral arteries (SpA) decreases utero-placental resistance drastically, allowing sustained and increased blood flow to the placenta at all circumstances. We systematically evaluated available reports to visualize adaptation of spiral arteries throughout pregnancy by ultra-sonographic measurements and evaluated when this process is completed.Methods: A systematic review and meta-analysis of spiral artery flow (pulsatility index (PI), resistance index (RI) and peak systolic velocity (PSV)) was performed. English articles were obtained from Pubmed, EMBASE and Cochrane Library and included articles were assessed on quality and risk of bias. Weighted means of Doppler indices were calculated using a random-effects model. Results: In healthy pregnancies, PI and RI decreased from 0.75 (95% CI: 0.67-0.83) and 0.49 (95% CI: 0.46-0.53) in the first trimester to 0.52 (95% CI: 0.48-0.56, p=0.003) and 0.40 (95% CI: 0.38-0.42, p=0.080) in the second trimester and to 0.49 (95% CI: 0.44-0.53, p=0.510) and 0.36 (95% CI: 0.35-0.37, p=0.307) in the third trimester, respectively. In parallel, PSV altered from 0.24 m/s (95% CI: 0.17-0.31 m/s) to 0.28 m/s (95% CI: 0.22-0.34 m/s, p=0.377) and to 0.25 m/s (95% CI: 0.21-0.28 m/s, p=0.919) in the three trimesters. In absence of second and third trimester Doppler data in complicated gestation, only a difference in PI was observed between complicated and healthy pregnancies during the first trimester (1.49 vs 0.76, p<0.001). Although individual studies have identified differences in PI between SpA located in the central part of the placental bed versus those located at its periphery, this meta-analysis could not confirm this (p=0.349).Conclusions: This review and meta-analysis concludes that an observed decrease of SpA PI and RI from the first towards the second trimester parallels the physiological trophoblast invasion converting SpA during early gestation, a process completed in the midst of the second trimester. Higher PI and RI were found in SpA of complicated pregnancies compared to healthy pregnancies, possibly reflecting suboptimal utero-placental circulation. Longitudinal studies examining comprehensively the predictive value of spiral artery Doppler for complicated pregnancies are yet to be carried out.

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Baboon placental heparin-binding epidermal growth factor-like growth factor

Reproduction ◽

10.1530/rep-19-0487 ◽

2020 ◽

Vol 160 (1) ◽

pp. 31-37

Author(s):

D Randall Armant ◽

Graham W Aberdeen ◽

Brian A Kilburn ◽

Gerald J Pepe ◽

Eugene D Albrecht

Keyword(s):

Growth Factor ◽

First Trimester ◽

Extravillous Trophoblast ◽

Immunocytochemical Staining ◽

Heparin Binding ◽

Spiral Artery ◽

Primate Model ◽

Artery Remodeling ◽

Egf Family

Placental extravillous trophoblast remodeling of the uterine spiral arteries is important for promoting blood flow to the placenta and fetal development. Heparin-binding EGF-like growth factor (HB-EGF), an EGF family member, stimulates differentiation and invasive capacity of extravillous trophoblasts in vitro. Trophoblast expression and maternal levels of HB-EGF are reduced at term in women with preeclampsia, but it is uncertain whether HB-EGF is downregulated earlier when it may contribute to placental insufficiency. A nonhuman primate model has been established in which trophoblast remodeling of the uterine spiral arteries is suppressed by shifting the rise in estrogen from the second to the first trimester of baboon pregnancy. In the present study, we used this model to determine if placental HB-EGF is altered by prematurely elevating estrogen early in baboon gestation. Uterine spiral artery remodeling and placental expression of HB-EGF and other EGF family members were assessed on day 60 of gestation in baboons treated with estradiol (E2) daily between days 25 and 59 of gestation (term = 184 days). The percentages of spiral artery remodeling were 90, 84 and 70% lower (P < 0.01), respectively, for vessels of 26–50, 51–100 and >100 µm diameter in E2-treated compared with untreated baboons. HB-EGF protein quantified by immunocytochemical staining/image analysis was decreased three-fold (P < 0.01) in the placenta of E2-treated versus untreated baboons, while amphiregulin (AREG) and EGF expression was unaltered. Therefore, we propose that HB-EGF modulates the estrogen-sensitive remodeling of the uterine spiral arteries by the extravillous trophoblast in early baboon pregnancy.

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Antenatal Mesenchymal Stromal Cell Extracellular Vesicle Treatment Preserves Lung Development in a Model of Bronchopulmonary Dysplasia Due to Chorioamnionitis

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00329.2021 ◽

2021 ◽

Author(s):

Alison Nicole Abele ◽

Elizabeth S Taglauer ◽

Maricar Almeda ◽

Noah Wilson ◽

Abigail Abikoye ◽

...

Keyword(s):

Bronchopulmonary Dysplasia ◽

Mesenchymal Stromal Cell ◽

Stromal Cell ◽

Lung Mechanics ◽

Spiral Artery ◽

Lung Growth ◽

Pulmonary Vessel ◽

Cesarean Section Delivery ◽

Distal Lung

Background: Antenatal stressors such as chorioamnionitis (CA) increase the risk for bronchopulmonary dysplasia (BPD). Studies have shown that experimental BPD can be ameliorated by postnatal treatment with mesenchymal stromal cell-derived extracellular vesicles (MEx). However, the antenatal efficacy of MEx to prevent BPD is unknown. Objective: To determine whether antenatal MEx therapy attenuates intrauterine inflammation and preserves lung growth in a rat model of CA-induced BPD. Methods: At embryonic day (E)20, rat litters were treated with intra-amniotic injections of saline, endotoxin (ETX) to model chorioamnionitis, MEx, or ETX plus MEx followed by cesarean section delivery with placental harvest at E22. Placental and lung evaluations were conducted at day 0 and day 14, respectively. To assess the effects of ETX and MEx on lung growth in vitro, E15 lung explants were imaged for distal branching. Results: Placental tissues from ETX-exposed pregnancies showed increased expression of inflammatory markers NLRP-3 and IL-1ß and altered spiral artery morphology. Additionally, infant rats exposed to intrauterine ETX had reduced alveolarization and pulmonary vessel density (PVD), increased right ventricular hypertrophy (RVH), and decreased lung mechanics. Intrauterine MEx therapy of ETX-exposed pups reduced inflammatory cytokines, normalized spiral artery architecture, and preserved distal lung growth and mechanics. In vitro studies showed that MEx treatment enhanced distal lung branching and increased VEGF and SPC gene expression. Conclusions: Antenatal MEx treatment preserved distal lung growth and reduced intrauterine inflammation in a model of CA-induced BPD. We speculate that MEx may provide a novel therapeutic strategy to prevent BPD due to antenatal inflammation.

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