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Objective:To investigate the association between folate levels and the risk of gestational diabetes mellitus (GDM) risk during the whole pregnancy.Design:In this retrospective cohort study of pregnant women, serum folate levels were measured before 24 gestational weeks (GW). GDM was diagnosed between 24th and 28th GW based on the criteria of the International Association of Diabetes and Pregnancy Study Groups. General linear models were performed to examine the association of serum folate with plasma glucose (i.e. linear regressions) and risk of GDM (i.e. log-binomial regressions) after controlling for confounders. Restricted cubic spline regression was conducted to test the dosage–response relationship between serum folate and the risk of GDM.Setting:A sigle, urban hospital in Shanghai, China.Participants:A total of 42 478 women who received antenatal care from April 2013 to March 2017 were included.Results:Consistent positive associations were observed between serum folate and plasma glucose levels (fasting, 1-h, 2-h). The adjusted relative risks (RR) and 95 % CI of GDM across serum folate quartiles were 1·00 (reference), 1·15 (95 % CI (1·04, 1·26)), 1·40 (95 % CI (1·27, 1·54)) and 1·54 (95 % CI (1·40, 1·69)), respectively (P-for-trend < 0·001). The positive association between serum folate and GDM remained when stratified by vitamin B12 (adequate v. deficient groups) and the GW of serum folate measurement (≤13 GW v. >13 GWs)Conclusions:The findings of this study may provide important evidence for the public health and clinical guidelines of pregnancy folate supplementation in terms of GDM prevention.

Pyruvate dehydrogenase kinase (PDK) is known as a gatekeeper directing the carbon flux into glycolysis via inhibition of the pyruvate dehydrogenase complex. During syncytialization of placental trophoblasts, both ATP production and oxygen consumption are increased to meet enhanced energetic demands by syntiotrophoblasts. We hypothesized that down-regulation of PDK expression may play a central role in the switch from glycolysis to oxidative phosphorylation (OXPHOS) during syncytialization. By using primary human trophoblasts, we demonstrated that PDK4 was the dominating PDK isoform in human cytotrophoblasts, and its abundance was substantially decreased upon syncytialization, which was accompanied by decreases in lactate production and increases in ATP production. Knock-down of PDK4 expression reduced lactate production and increased ATP production, while over-expression of PDK4 increased lactate production and decreased ATP production, indicating that down-regulation of PDK4 is key to the shift from glycolysis to OXPHOS during syncytialization. Moreover, human chorionic gonadotropin (hCG)/cAMP/PKA pathway was demonstrated to be involved in the down-regulation of PDK4 expression upon syncytialization. Taken together, our findings disclosed that down-regulation of PDK4 is critical for the metabolic shift from glycolysis to OXPHOS during syncytialization, which may be a prerequisite for the proper implementation of syncytiotrophoblast functions.

PROBLEM Rupture of fetal membranes is a crucial event at parturition, which is preceded by extensive extracellular matrix (ECM) remodeling. Our recent studies have demonstrated that the human fetal membranes are capable of de novo synthesis of serum amyloid A1 (SAA1), an acute phase protein, and the abundance of SAA1 in the amnion was increased at parturition. However, the exact role of SAA1 in human parturition remains to be established. METHOD OF STUDY The effects of SAA1 on the abundance of collagenases and lysyl oxidase, the enzyme that cross-links collagens, were investigated in culture primary human amnion fibroblasts and tissue explants with an aim to examine the involvement of SAA1 in the ECM remodeling in the amnion. RESULTS Serum amyloid A1 (SAA1) time- and dose-dependently increased the abundance of collagenases MMP-1, MMP-8, and MMP-13, while decreased the abundance of lysyl oxidase-like 1 (LOXL1). These effects of SAA1 were attenuated by siRNA-mediated knockdown of the Toll-like receptor (TLR) 4 and its antagonist CLI-095, but not by siRNA-mediated knockdown of TLR2. Furthermore, the inhibitors for NF-κB (JSH-23) and mitogen-activated protein kinases (MAPKs) p38 (SB203580) and JNK (SP600125) could also attenuate the effects of SAA1, while the inhibitor for MAPK ERK1/2 (PD 98059) could block the effects of SAA1 only on MMP-1, MMP-8, and LOXL1 but not on MMP-13. CONCLUSION These data highlight a possible role for SAA1 in ECM remodeling preceding membrane rupture by regulating the expression of collagenases MMP-1, MMP-8, MMP-13, and LOXL1 through TLR4-mediated activation of the NF-κB and MAPK pathways in amnion fibroblasts.

To investigate the impact of danazol alginate microspheres used for uterine arterial embolization (UAE) on ovarian function and subsequent pregnancy using rabbit as a model.A total of 32 female rabbits were divided into 3 groups: a control group, danazol alginate microspheres (DKMG) group and alginate microspheres (KMG) group. Basal serum estradiol (E(2)), follicle stimulating hormone (FSH), luteinizing hormone (LH), testosterone (T) levels before UAE and 1 - 3 months after UAE were compared for all rabbits. In breeding field all rabbits mated after UAE. Estrus, and pregnancy rate were observed by veterinary.There were no significant changes from baseline FSH, LH, E(2), T levels measured at 1, 2 and 3 months after UAE (P0.05). The total pregnancy rate of DKMG or KMG group was 0 within 2 - 4 months after UAE. Compared to the control group (4/8), the difference was statistically significant (P0.05); the total pregnancy rate of DKMG, KMG and control groups within 5 - 7 months after UAE, respectively 17% (2/12), 25% (3/12) and 5/8 (P0.05); the total pregnancy rate was 42% (5/12), 50% (6/12) and 6/8 respectively within 8 - 10 months after UAE, there were also no significant differences between the three groups (P0.05).There is no obvious effect of danazol alginate microspheres used for uterine arterial embolization on ovarian function in rabbits. After UAE some animals are able to achieve pregnancies, while harmful effects are observed on short term pregnant rate.