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Hyperglycemia Hinders First Trimester Cytotrophoblast Migration and Induces Apoptosis
Author(s) -
Cawyer C,
Yuen S,
Pantho A,
Drever N,
Beeram M,
Zawieja D,
Kuehl T,
Uddin M
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.569.3
Subject(s) - ctbs , apoptosis , signal transduction , p38 mitogen activated protein kinases , phosphorylation , endocrinology , microbiology and biotechnology , smad , medicine , mapk/erk pathway , receptor , chemistry , biology , biochemistry , metaplasticity , synaptic plasticity
Objective Approximately 20% of the diabetic pregnant women develop preeclampsia (preE). In a recent study, we have shown that hyperglycemia impairs CTB function via stress signaling. In the present study, we assess the CTBs apoptotic signaling. Study Design: Human extravillous CTBs were treated with 0, 100, 200, 300 or 400 mg/dL glucose for 48h. Some cells were pretreated with a p38 inhibitor or a peroxisome proliferator‐activated receptor gamma (PPARγ) ligand. Other cells were treated with D‐Mannitol. Cell migration was performed by Matrigel migration kit. Cell lysates were utilized to measure PPARγ, p38 MAPK phosphorylation, and apoptotic signaling proteins; Bcl‐2‐associated X protein (Bax), anti‐apoptotic Bcl‐2 and caspase‐9 and cyclooxygenase‐2 (Cox‐2) by western blot. Results CTBs migration was inhibited by 蠅 150 mg/dL of glucose compared to basal (100 mg/dL) (p<0.05). The p38 MAPK phosphorylation and PPARγ were upregulated (p<0.05) in CTBs treated with >150 mg/dL glucose. The expression of Bax/Bcl‐2, Cox‐2, caspase‐9 were up‐regulated (p<0.05) in CTBs treated with 蠅100 mg/dL glucose. The SB203580 or rosiglitazone pretreatment showed an attenuation of hyperglycemia‐induced apoptotic signaling proteins. D‐Mannitol had no effect on CTBs. Conclusions Hyperglycemia inhibited the migration of CTBs and induced the apoptotic signaling in CTBs. The attenuation of hyperglycemia‐induced apoptotic signaling suggests the involvement of apoptotic signaling mechanisms in CTBs dysfunction.