Effect of an individualised nutritional intervention on gestational diabetes mellitus prevention in a high-risk population screened by a prediction model: study protocol for a multicentre randomised controlled trial.

BACKGROUND: The ability of a preventive nutritional intervention to reduce the morbidity of gestational diabetes mellitus (GDM) remains controversial. We aim to assess whether GDM can be prevented by an individualised nutritional intervention in pregnant women who are at high risk for the disease based on a prediction model. METHODS/DESIGN: A multicentre randomised controlled trial was designed to assess the efficacy of an individualised nutritional intervention for the prevention of GDM in a high-risk population screened by a novel prediction model in the first trimester. Pregnant women evaluated to be at high risk for GDM by the prediction model at less than 14 gestational weeks will be included. Women with pre-existing chronic diseases, including pregestational diabetes, or who are currently prescribed medicines that affect glucose values will be excluded. Allocation to intervention/control at a ratio of 1:1 will be conducted by a computerized randomisation system. The intervention group will complete 3-day food records and receive 3 individualised nutritional consultations with professional dieticians before the oral glucose tolerance test. The primary intention of the intervention is to promote a long-term healthy dietary pattern and prevent excessive gestational weight gain throughout pregnancy. The control group will complete 3-day food records at designated gestational weeks and receive standard antenatal care according to local health care provisions. The primary outcome is the incidence of GDM according to the criteria of the International Association of Diabetes and Pregnancy Study Group (IADPSG). A sample of 464 participants will provide 80% power to detect a 30% reduction in GDM incidence (α = 0.05 two tailed, 10% dropout). A total of 500 participants will be recruited. DISCUSSION: To date, this is the first randomised controlled trial aimed to evaluate the protective effect of an individualised nutritional intervention against GDM based on a logistic regression prediction model. Eligibility is not limited to obese women or singleton pregnancies, as in previous studies. This pragmatic trial is expected to provide valuable information on early screening and effective GDM prevention methods. TRIAL REGISTRATION NUMBER: ChiCTR, ChiCTR1900026963 . Registered 27 October 2019.

The YY1-HOTAIR-MMP2 Signaling Axis Controls Trophoblast Invasion at the Maternal-Fetal Interface.

We aimed to determine the effect of YY1 expression on the expression profile of long noncoding RNAs (lncRNAs) in trophoblasts, and we studied the involvement of certain lncRNAs and YY1 in the pathogenesis of recurrent miscarriage (RM). RT2 lncRNA PCR arrays revealed that YY1 overexpression in trophoblasts significantly promoted the expression of the HOX transcript antisense RNA HOTAIR and demonstrated that HOTAIR expression was significantly lower in the RM trophoblasts than in control trophoblasts. Ectopic HOTAIR overexpression and knockdown experiments revealed that it was a novel target of YY1. Bioinformatics analysis identified two YY1-binding sites in the HOTAIR promoter region, and chromatin immunoprecipitation (ChIP) analysis verified that YY1 binds directly to its promoter region. Interestingly, HOTAIR overexpression enhanced trophoblast invasion in an ex vivo explant culture model, while its knockdown repressed these effects. Furthermore, liquid chromatography-tandem mass spectrometry (LC-MS/MS) label-free quantitative proteomics screening revealed that HOTAIR overexpression activated phosphatidylinositol 3-kinase-protein kinase B (PI3K-AKT) signaling in trophoblasts. In an ex vivo explant culture model, HOTAIR overexpression effectively elevated matrix metalloproteinase 2 (MMP2) expression via the PI3K-AKT signaling pathway, enhancing trophoblast migration and invasion. These findings reveal a new regulatory pathway in which YY1 activates PI3K-AKT signaling via HOTAIR, promoting MMP2 expression, suggesting that HOTAIR is a potential therapeutic target for RM.