Amniotic LPS-Induced Apoptosis in the Fetal Brain Is Suppressed by Vaginal LPS Preconditioning but Is Promoted by Continuous Ischemic Reperfusion.

Yupeng Dong,Nobuo Yaegashi,Yoshitaka Kimura

doi:10.3390/ijms23031787

Yupeng Dong, Nobuo Yaegashi + Show 1 more

Open Access

https://doi.org/10.3390/ijms23031787

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Abstract

Chorioamnionitis (CAM) is an increasingly common disease affecting pregnant women which derives from bacterial vaginosis. In different clinical cases, it has been shown that CAM can cause multiple risk factors for fetal brain damage, such as infection, and intra-uterine asphyxia. However, the molecular mechanism remains unknown. In this study, we established a novel CAM mouse model by exposing pregnant mice to a combination of three risk factors: vaginal lipopolysaccharides (LPS), amniotic LPS, and ischemic reperfusion. We found amniotic LPS caused Parkinson’s disease-like fetal brain damage, in a dose and time-dependent manner. Moreover, the mechanism of this fetal brain damage is apoptosis induced by amniotic LPS but it was inhibited by being pretreated with a vaginal LPS challenge before amniotic LPS injection. In contrast, amniotic LPS with continuous ischemic reperfusion caused a higher level of apoptotic cell death than amniotic LPS alone. In particular, a potential neuroprotective biomarker phosphorylation (p)-CREB (ser133) appeared in only vaginal LPS preconditioned before amniotic LPS, whereas ischemic reperfusion triggered IKK phosphorylation after amniotic LPS. Despite the need for many future investigations, this study also discussed a developed understanding of the molecular mechanism of how these phenotypes occurred.

Highlights

The prevalence of Bacterial vaginosis (BV) in the general population is high globally, ranging from 23% to 29% across regions (Europe and Central Asia, 23%; East Asia and Pacific, 24%; Latin America and Caribbean, 24%; Middle East and North Africa, 25%; sub-Saharan Africa, 25%; North America, 27%; South Asia, 29%) [1,2,3,4]
Transplantation of fetal brain cells has been used as a potential therapy for Parkinson disease, fetal brain damage or cerebral palsy, may result from different risk factors including gestational age of
We first reported that p-ATF1/p-CREB (Ser133) presented in the Vaginal LPS plus amniotic fluid LPS (VAF) group (Figure 5), whereas p-JNK/p-ATF2 (Thr71) and p-ATF1/p-CREB (Ser133) were activated in after 3 h (AF3h) (Figure 4D)

Summary

Introduction

The prevalence of Bacterial vaginosis (BV) in the general population is high globally, ranging from 23% to 29% across regions (Europe and Central Asia, 23%; East Asia and Pacific, 24%; Latin America and Caribbean, 24%; Middle East and North Africa, 25%; sub-Saharan Africa, 25%; North America, 27%; South Asia, 29%) [1,2,3,4]. Compared with other models, such as the preterm brain damage model [13,14], the infectious preterm chorioamnionitis model [15], and the LPS induced maternal systematic to fetal inflammation model [16,17,18,19,20,21,22], our mouse model was only designed to mimic increasing inflammation at term. Reviews have shown that it is hard to attain consensus by comparing individual studies, as during brain development, infection and inflammation or ischemic reperfusion, have a variable pathological course, resulting in a range of phenotypes [11,23]. Further investigation of the molecular mechanism is required to clarify the pathological processes of fetal brain damage induced by multiple factors

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