ObjectiveTo assess the associations of gestational weight gain (GWG) in early and late pregnancy with subsequent risks of adverse pregnancy outcomes in Chinese women.DesignProspective cohort study.SettingShanghai, China.ParticipantsWe studied 2630 nulliparous singleton pregnant women with complete data on weight gain in early (≤17 weeks of gestation) and late (>17 weeks) pregnancy in the Shanghai Birth Cohort.MethodsGWG was standardised into z-scores by gestational age and categorised as low (z-score <−1), normal (−1 to +1) and high (>1). The adjusted relative risks (aRRs) and 95%CIs were estimated through log-binomial regression models. Interaction effects between GWG and some other adjustment factors were tested, further stratified analyses were performed separately where interaction terms were significant.Outcome measuresAdverse maternal and neonatal outcomes.ResultsIndependent from GWG in late pregnancy, higher GWG in early pregnancy was associated with higher risks of gestational diabetes mellitus (aRR: 1.66; 95% CI: 1.11 to 2.48), caesarean section (aRR: 1.21; 95% CI: 1.05 to 1.39) and prolonged hospitalisation (aRR: 1.56; 95% CI: 1.03 to 2.38). Higher GWG in late pregnancy was independently associated with higher risks of caesarean section (aRR: 1.24; 95% CI: 1.09 to 1.41), large for gestational age (aRR: 2.01; 95% CI: 1.50 to 2.7) and macrosomia (aRR: 1.90; 95% CI: 1.30 to 2.78). In addition, the risk of gestational hypertension increased significantly with increased total GWG (aRR: 1.78; 95% CI: 1.14 to 2.76). The effects of GWG in late pregnancy on maternal and neonatal outcomes were significantly different between the women bearing a female and the women bearing male fetus.ConclusionThe GWG associations with adverse pregnancy outcomes differ at early and late pregnancy, and there may be effect modification by fetal sex in the association of GWG in late pregnancy with some pregnancy outcomes.

Preeclampsia (PE) affects 3 to 5% of pregnant women worldwide and is associated with fetal and maternal morbidity and mortality. Although a complete understanding of PE remains elusive, it has been widely accepted that a dysfunction of the placenta plays a key role in the pathogenesis of PE. In this study, we investigated the role of excessive placental autophagy during PE pathogenesis and explored whether esomeprazole ameliorates PE by inhibiting the autophagy in the placenta. The PE cellular model was established by treating the cells’ L-NAME and hypoxia. The PE mice model was established by L-NAME administration and was confirmed by the increased systolic blood pressure (SBP) and urinary protein detected. The autophagy and key proteins were detected in human placental tissue, in cells, and in the mice model by Western blot and immunofluorescence staining. Results showed that excessive autophagy could be detected in human PE placental tissue, in the PE cellular model, and in the PE mice model. Hypoxia induces autophagy by activating AMPKα and inhibiting mTOR in vivo and in vitro. Esomeprazole inhibits L‐NAME-induced autophagy in mice by inhibiting AMPKα and activating mTOR. In conclusion, this study demonstrates that the excessive autophagy induced by the SIRT1/AMPKα-mTOR pathway plays a significant role in the pathogenesis of PE. However, esomeprazole treatment inhibits AMPKα but activates mTOR, resulting in the inhibition of autophagy in the placenta and, therefore, mitigates PE symptoms.

Pre-eclampsia (PE) is closely associated with perinatal morbidity and mortality and we want to investigate tetramethylpyrazine (TMP)'s effects on PE. Pregnant Sprague-Dawley rats were randomly divided into five groups: normal pregnant (PC), PE, PE+TMP 20 mg/kg, PE+TMP 40 mg/kg, and PE+TMP 60 mg/kg group. The PE rat model was established via L-NAME treatment. Systolic blood pressures (SBP) and urinary protein concentration were detected via the tail-cuff method and CBB kit, respectively. mRNA levels of key genes were analyzed via quantitative PCR and protein levels of key genes were measured by ELISA or western blot. TMP decreased SBP and urinary protein concentration of PE rats. TMP inhibited L-NAME-induced decrease in pups alive ratio, pups weight, and the ratio of pups/placenta weight and reversed L-NAME induced changes in placental histology, whereas it had little effect on placental weight. Urinary nephrin and podocin expressions were enhanced and serum placental growth factor level was decreased in PE rats, whereas TMP inhibited the above phenomena. TMP suppressed L-NAME-induced sFlt-1 upregulation in serums and kidneys of PE rats, whereas it downregulated IL-6 and MCP-1 expression in PE rats' serums, placentas and kidneys. TMP also suppressed the increase in placental sFlt-1 and vascular endothelial growth factor level caused by L-NAME. In addition, TMP inhibited CHOP and GRP78 expressions and decreased the ratio of p-elF2α/elF2α in PE rats. TMP attenuated the consequences of NO inhibition in pregnant rats. K E Y W O R D SER stress, hypertension, pre-eclampsia, proteinuria, tetramethylpyrazine

To investigate the potential beneficial effect of insulin‐like growth factor‐1 (IGF‐1) in BMSC transplantation therapy of uterus injury and the underlying molecular mechanisms, rat BMSCs were isolated and cultured. The relative expressions of IGF‐1 and IL‐10 were determined by RT‐PCR and immunoblotting. The secretory IL‐10 and released E2 were measured using ELISA kits. The relative vWF and α‐SMA expressions were determined by immunohistochemistry. The direct binding of NF‐κB subunit p50 with IL‐10 promoter was analysed by chromatin immunoprecipitation assay. The regulation of IL‐10 expression by p50 was interrogated by luciferase reporter assay. Our data demonstrated that IGF‐1 expression in BMSCs induced IL‐10 expression and secretion, which was further enhanced by E2‐PLGA. IGF‐1 overexpression improved BMSCs transplantation therapy in rat uterus injury. We further demonstrated that both inhibition and knockdown of p50 abolished IGF‐1‐induced expression and secretion of IL‐10 in BMSCs, which consequently compromised the IGF‐1 conferred therapeutic benefits against uterus injury. Furthermore, we elucidated that p50 regulated IL‐10 expression via direct association with its promoter. Our data suggested that transplantation of IGF‐1 overexpressing BMSCs improved functional regeneration of injured uterus by inducing IL‐10 expression and secretion via activation of NF‐κB signalling.

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It is widely reported that microRNAs (miRNAs, miRs) play critical roles in the occurrence and development of peripartum cardiomyopathy (PPCM). Here, we aimed to explore the biological role of miR-874 and its underlying mechanisms in PPCM. To this purpose, a mouse model of PPCM was established through cardiac-specific overexpression of Gαq. Transthoracic echocardiography and left ventricular catheterization were used to examine the cardiac functions and hemodynamics. Apoptosis of the cardiomyocytes was determined by the terminal deoxynucleotidyl transferase dUTP nick end labeling assay. The direct interaction between miR‐874 and signal transducer and activator of transcription 3 (STAT3) was confirmed by luciferase assay. The expression of apoptosis-related genes and proteins was evaluated by real-time quantitative reverse transcription polymerase chain reaction and Western blot, respectively. The results demonstrated that miR-874 inhibition significantly increased the survival and cardiac functions of pregnant Gαq transgenic mice. In addition, miR-874 inhibitor ameliorated cardiomyocyte apoptosis, downregulated both mRNA and protein levels of Bax, while upregulated those of Bcl-2. Further, STAT3 was found to be a direct target of miR-874. In addition, miR-874 inhibition increased the expression of STAT3 and janus kinase 2. In summary, miR-874 inhibition could improve cardiac functions and suppress cardiomyocyte apoptosis by targeting STAT3 during PPCM in Gαq transgenic mice.