Vitamin D facilitates trophoblast invasion through induction of epithelial‐mesenchymal transition

Kim, Ryang Hee; Ryu, Beyong Hwan; Lee, Ki Mo; Han, Jae Won; Lee, Sung Ki

doi:10.1111/aji.12796

Cited by 16 publications

(14 citation statements)

References 37 publications

(37 reference statements)

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“…Although DBP plays a pivotal role in defining the matrix invasion by trophoblastic cells, our data also indicate a role for DBP's cargo. Active vitamin D, 1,25D, promoted trophoblast matrix invasion consistent with previous studies of trophoblast cells (Chan, et al 2015;Kim et al 2018). This effect was independent of the nuclear VDR and trophoblast cells did not exhibit classical 1,25D-VDR responses such as induction of CYP24A1, but instead promoted non-nuclear signalling via induction of pERK.…”

supporting

confidence: 90%

Trophoblast uptake of DBP regulates intracellular actin and promotes matrix invasion

Ganguly

Tamblyn

Shattock

et al. 2021

Journal of Endocrinology

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Early pregnancy is characterised by elevated circulating levels of vitamin D binding protein (DBP). The impact of this on maternal and fetal health is unclear but DBP is present in the placenta, and DBP gene variants have been linked to malplacentation disorders such as preeclampsia. A functional role for DBP in the placenta was investigated using trophoblastic JEG3, BeWo and HTR8 cells. All three cells lines showed intracellular DBP, with increased expression and nuclear localisation of DBP in cells treated with the active form of vitamin D, 1,25-dihydroxyvitamin D (1,25D). When cultured in serum from mice lacking DBP (DBP-/-), JEG3 cells showed no intracellular DBP indicating uptake of exogenous DBP. Inhibition of the membrane receptor for DBP, megalin, also suppressed intracellular DBP. Elimination of intracellular DBP with DBP-/- serum or megalin inhibitor suppressed matrix invasion by trophoblast cells, and was associated with increased nuclear accumulation of G-actin. Conversely, treatment with 1,25D enhanced matrix invasion. This was independent of the nuclear vitamin D receptor but was associated with enhanced ERK phosphorylation, and inhibition of ERK kinase suppressed trophoblast matrix invasion. When cultured with serum from pregnant women, trophoblast matrix invasion correlated with DBP concentration, and DBP was lower in first trimester serum from women who later developed preeclampsia. These data show that trophoblast matrix invasion involves uptake of serum DBP and associated intracellular actin binding and homeostasis. DBP is a potential marker of placentation disorders such as preeclampsia and may also provide a therapeutic option for improved placenta and pregnancy health.

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supporting

confidence: 90%

Trophoblast uptake of DBP regulates intracellular actin and promotes matrix invasion

Ganguly

Tamblyn

Shattock

et al. 2021

Journal of Endocrinology

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“…During early placental development, extravillous cytotrophoblasts acquire proliferative, migratory, and invasive capabilities necessary to ensure sufficient supply of blood, oxygen, and nutrients to the fetus. These capabilities are very similar to those required for tumour invasion 24,25 . The presence of fetal trophoblastic cells in maternal blood is no longer considered controversial 26 and have been used for noninvasive prenatal diagnosis for decades 27‐29 .…”

Section: Discussionmentioning

confidence: 97%

Differential expression of SALL4 in CTCs derived from hydatidiform moles and gestational trophoblastic neoplasms

Feng

Pei

et al. 2020

American J Rep Immunol

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Problem To investigate EMT phenotype and SALL4 expression of circulating tumour cells (CTCs) in patients with gestational trophoblastic neoplasm (GTN). Method of study CanPatrol CTC detection system in combination with SALL4 RNA in situ hybridization was used to investigate the profile of CTCs in different types of gestational trophoblastic disease (GTD). Circulating CTCs were phenotyped and annotated with SALL4 expression in 41 GTD patients, including 12 HM and 29 GTN, as well as 22 pregnant volunteers. Results A positive correlation between the number of CTC and serum β‐hCG concentration was found among the GTN patients. The number of E/M‐CTC was positively correlated with serum β‐hCG, while M‐CTC was positively correlated with prognostic score. Comparison among malignant GTD, benign GTD and healthy pregnant women revealed a significant difference in the number of total CTC, E/M‐CTC, and M‐CTC but not in E‐CTC. ROC analysis was conducted to evaluate the performance of CTC phenotypes in distinguishing GTD patients from healthy pregnant women yielding an AUC as 0.826. Youden's index was maximal at the cutoff value of 8.5/4 mL with sensitivity and specificity at 53.66% and 100%, respectively. SALL4 expression was evaluated in GTD patients with CTC count greater than cutoff value. SALL4 high expressing CTCs (>2 signal dots) were detected in 66.67% (10/15) of malignant GTD patients but not in benign patients (0/5). Conclusion Differential expression of SALL4 was seen in CTCs derived from hydatidiform moles and GTN. CTC profiling may be developed as an adjunct marker to diagnose GTN.

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“…Vitamin D influences folliculogenesis, modulates endometrial receptivity, and regulates embryogenesis [45]. It plays an important role in trophoblast invasion [46]. There are plenty of studies that prove its effects on placental implantation, angiogenesis and endothelial function, immune function, inflammatory response during pregnancy, oxidative stress, and glucose homeostasis [47][48][49][50][51][52][53].…”

Section: Vitamin D -Role In Uncomplicated Pregnancymentioning

confidence: 99%

The role of vitamin D in perinatology. An up-to-date review

et al. 2021

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The role of vitamin D in perinatology is a subject of major interest in current medicine. There is growing evidence about the role of maternal vitamin D levels in pregnancy outcomes. The aim of this review is to summarize the current literature about the role of vitamin D in perinatology. Evidence from this review suggests associations between low levels of maternal vitamin D and higher risk of certain obstetrical complications. Vitamin D has been found to be related to preeclampsia, gestational diabetes mellitus, low birth weight, and preterm birth. The current literature supports vitamin D supplementation in pregnant women, but more high-quality data are necessary. The problem that remains is how to achieve an optimal 25-hydroxyvitamin D level. To determine the real benefits of vitamin D supplementation in pregnancy, we need high-quality trials in larger groups.

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Vitamin D facilitates trophoblast invasion through induction of epithelial‐mesenchymal transition

Abstract: Calcitriol facilitated EMT induction and expression of MMPs via ERK signaling pathway, which promoted the invasive capability of EVTs. Further studies are warranted to elucidate the potential application of vitamin D in the prevention of pregnancy complications.

Cited by 16 publications

References 37 publications

Trophoblast uptake of DBP regulates intracellular actin and promotes matrix invasion

Trophoblast uptake of DBP regulates intracellular actin and promotes matrix invasion

Differential expression of SALL4 in CTCs derived from hydatidiform moles and gestational trophoblastic neoplasms

The role of vitamin D in perinatology. An up-to-date review

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