Project description:In this study, the molecular signature of placenta membrane from preterm birth placenta was assessed and compared to full-term placenta by proteomic profiling with the aim to identify molecules relevant to preterm birth.
Project description:Placental insufficiency is implicated in the intrauterine infection-associated spontaneous preterm birth. Using a mouse model of LPS-induced intrauterine inflammation that leads to preterm delivery, RNA-seq study was performed in the placenta at gestational day 17 to assess the transcriptome changes.
Project description:Preterm birth is a leading cause of neonatal mortality and lacks an effective therapy. Ascending microbial infections from the lower genital tract lead to infection of the placenta, amniotic fluid and fetus causing preterm birth or stillbirth. Directly in the path of an ascending infection is the cervical mucus plug (CMP), a dense mucoid structure in the cervical canal with potential antimicrobial properties. In this study, we aimed to define the components of CMP responsible for antimicrobial activity against a common lower genital tract organism associated with preterm birth and stillbirths, namely Group B Streptococcus (GBS). Using a quantitative proteomic approach, we identified antimicrobial factors in CMPs that were collected from healthy human pregnancies. This study aims to provide new insight into how the human CMP may limit ascending bacterial infection.
Project description:Placenta is essential for reproductive success and placental abnormalities are the leading cause of low birth weight and preterm birth. The placenta includes polyploid cells that are crucial for its function. Polyploidy occurs broadly in nature but the regulators that enable polyploidy to arise in a spatiotemporally regulated manner in the placenta are unknown. We used scRNA seq to understand molecular regulators of polyploidy.
Project description:The prevalence of preterm birth along with its associated mortality and lifelong morbidity warrant a better understanding of the underlying signaling events for better diagnosis and management of the condition. Placenta is an important transient organ that acts as a conduit between the fetus and mother. Any physiological and pathological changes taking place in the feto-maternal system are directly reflected in the placenta, making it a fitting choice to study the altered signaling mechanisms that are play. We undertook independent data acquisition of clinical placenta samples (n=40), obtained from Garbh-Ini cohort, to study their comparative protein profiles in spontaneous preterm vs term birth condition. When label-free quantitation (LFQ) was carried out, it yielded 23 differentially expressed proteins (DEPs) in the case-control comparison.
Project description:Here, it is shown that YTHDC1 was significantly increased in the human preterm placenta after ART and the murine preterm placenta after E2 exposure. Overexpression of YTHDC1 significantly promoted the proliferation, migration, and invasion of trophoblast cells, but inhibited their apoptosis. Knockdown or knockout of YTHDC1 played an opposite effect. Mechanistically, E2 promoted YTHDC1 expression through retinoid X receptor alpha (RXRA) upregulation. YTHDC1 could activate WNT and JAK/STAT signaling pathways in the human trophoblast cells. Meanwhile, YTHDC1 could fine-tone the translation of ribosomal protein L37 (RPL37) in a m6A-dependent manner, which then influence the cellular total protein synthesis. Importantly, administration of siRNA targeting YTHDC1 effectively delays preterm birth in vivo. Collectively, these findings uncover the epigenetic mechanism underlying ART preterm birth and provide a potential target for therapeutic intervention.
