CpG Oligodeoxynucleotides Downregulate Placental Adiponectin and Increase Embryo Loss in Non‐Obese Diabetic Mice

Abstract

ProblemCpG oligodeoxynucleotides (ODNs) can induce immunological changes in non‐obese diabetic (NOD) mice and increase embryo loss, but little is known about the mechanism. This study aimed to determine the role of adiponectin in CpG ODN‐induced pregnancy failure.Method of studyOligodeoxynucleotide 1826 was intraperitoneally injected to NOD mice, and ODN 2216, ODN 2006, and ODN 2395 were used to stimulate human trophoblast cell lines to investigate adiponectin expression patterns and its possible effects on trophoblast function.ResultsCpG ODNs downregulated adiponectin via the cJun N‐terminal kinase signaling pathway and led to increased embryo loss (from 6.9 to 33.3%). ODN 2006 impaired human trophoblast cell migration, which was successfully rescued by adiponectin treatment.ConclusionCpG ODNs decreased placental adiponectin expression in NOD mice and impaired human trophoblast function and was associated with increased embryo loss. Adiponectin may therefore play an important protective role in the prevention of bacteria‐induced pregnancy failure.

Role of peroxiredoxin2 downregulation in recurrent miscarriage through regulation of trophoblast proliferation and apoptosis

“…SB202190 is a selective inhibitor of p38 MAP kinase which specially inhibits the p38 α and β isoforms, while SP600125 is a novel and selective inhibitor of JNK. 41 , 42 , 43 These two kinases are closely implicated in the regulation of apoptosis, inflammation, and cell cycle progression thus their functions always overlap with each other. 42 The different effects of SB202190 and SP600125 offer a solution to distinguish between p38-MAPK and JNK activated signal events.…”

“…Multiple groups were analyzed by one-way ANOVA with post hoc Tukey’s test. 41 Correlations were analyzed using Spearman’s rank correlation test. All P -values are two-sided, and P <0.05 was considered to indicate statistical significance.…”

Effect of the p53–tristetraprolin–stathmin-1 pathway on trophoblasts at maternal–fetal interface

“…Then, 5% non-fat milk in Tris-buffered saline with Tween (TBST) was used to block the PVDF membranes for 1 h at room temperature. The membranes were incubated with antibodies against STMN1 (1:2000; Abcam), TTP (1:500; Abcam), p53 (1:1000; Cell Signaling Technology), p-p53 (1:1000; Cell Signaling Technology), p21 (1:1000; Cell Signaling Technology), α-tubulin (1:1000; Yeasen, Shanghai, China), or GAPDH (1:1000; Cell Signaling Technology) overnight at 4°C, followed by horseradish peroxidase (HRP)-conjugated secondary antibody (1:2000; Yeasen) for 1 h. Signals were detected using a Prolight HRP chemiluminescent kit (Tiangen Biotech, Beijing, China) according to the manufacturer’s instructions [ 27 ].…”