Objective: To characterize the relationship between the levels of plasma methyl donor and related metabolites (including choline, betaine, methionine, dimethylglycine and homocysteine) and fetal growth in twin pregnancies. Methods: A hospital-based cohort study was used to collect clinical data of 92 pregnant women with twin pregnancies and their fetuses who were admitted to Peking University Third Hospital from March 2017 to January 2018. Fasting blood was collected from the pregnant women with twin pregnancies (median gestational age: 18.9 weeks). The levels of methyl donors and related metabolites in plasma were quantitatively analyzed by high-performance liquid chromatography combined with mass spectrometry. The generalized estimation equation was used to analyze the relationship between maternal plasma methyl donors and related metabolites levels and neonatal outcomes of twins, and the generalized additive mixed model was used to analyze the relationship between maternal plasma methyl donors and related metabolites levels and fetal growth ultrasound indicators. Results: (1) General clinical data: of the 92 women with twin pregnancies, 66 cases (72%) were dichorionic diamniotic (DCDA) twin pregnancies, and 26 cases (28%) were monochorionic diamniotic (MCDA) twin pregnancies. The comparison of the levels of five plasma methyl donors and related metabolites in twin pregnancies with different basic characteristics showed that the median levels of plasma choline and betaine in pregnant women ≥35 years old were higher than those in pregnant women <35 years old, and the differences were statistically significant (all P<0.05). (2) Correlation between plasma methyl donor and related metabolites levels and neonatal growth indicators: after adjusting for confounding factors, plasma homocysteine level in pregnant women with twins was significantly negatively correlated with neonatal birth weight (β=-47.9, 95%CI:-94.3- -1.6; P=0.043). Elevated methionine level was significantly associated with decreased risks of small for gestational age infants (SGA; OR=0.5, 95%CI: 0.3-0.9; P=0.021) and low birth weight infants (OR=0.6, 95%CI: 0.4-0.9; P=0.020). Increased homocysteine level was associated with increased risks of SGA (OR=1.5, 95%CI: 1.0-2.2; P=0.029) and inconsistent growth in twin fetuses (OR=1.9, 95%CI: 1.0-3.7; P=0.049). (3) Correlation between the levels of plasma methyl donors and related metabolites and intrauterine growth indicators of twins pregnancies: for every 1 standard deviation increase in plasma choline level in pregnant women with twin pregnancies, fetal head circumference, abdominal circumference, femoral length and estimated fetal weight in the second trimester increased by 1.9 mm, 2.6 mm, 0.5 mm and 20.1 g, respectively, and biparietal diameter, abdominal circumference and estimated fetal weight increased by 0.7 mm, 3.0 mm and 38.4 g in the third trimester, respectively, and the differences were statistically significant (all P<0.05). (4) Relationship between plasma methyl donor and related metabolites levels in pregnant women with different chorionicity and neonatal birth weight and length: the negative correlation between plasma homocysteine level and neonatal birth weight was mainly found in DCDA twin pregnancy (β=-65.9, 95%CI:-110.6- -21.1; P=0.004). The levels of choline, betaine and dimethylglycine in plasma of MCDA twin pregnancy were significantly correlated with the birth weight and length of newborns (all P<0.05). Conclusion: Homocysteine level is associated with low birth weight in twins, methionine is associated with decreased risk of SGA, and choline is associated with fetal growth in the second and third trimesters of pregnancy.
Adult ; Female ; Humans ; Infant, Newborn ; Pregnancy/metabolism* ; Betaine/metabolism* ; Birth Weight/physiology* ; Choline/metabolism* ; Cohort Studies ; Fetal Development/physiology* ; Fetal Weight/physiology* ; Homocysteine/metabolism* ; Methionine/metabolism* ; Pregnancy, Twin/physiology* ; Biomarkers/metabolism* ; Pregnancy Trimesters/physiology* ; Pregnancy Outcome

Sleep deprivation (SD) has many deleterious health effects and occurs in more than 70% of pregnant women. However, the changes in sex hormones and relevant mechanisms after SD have not been well clarified. The aim of the present study was to explore the effects of SD on the secretion of sex hormones and the underlying mechanisms. Twelve pregnant Wistar rats were divided into control (CON, n = 6) and SD (n = 6) groups. Pregnant rats in the SD group were deprived of sleep for 18 h, and allowed free rest for 6 h, and then the above procedures were repeated until delivery. The CON group lived in a 12 h light/dark light cycle environment. Estradiol (E2) and progesterone (P4) levels were detected by enzyme-linked immunosorbent assay (ELISA), and the expression of circadian clock genes, Bmal1, Clock and Per2, in hypothalamus and pituitary gland tissues were evaluated by immunohistochemistry (IHC) and reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The PI3K and Akt phosphorylation levels in the hypothalamic and pituitary tissues were determined by Western blot. The results showed that, compared with the CON group, the SD group exhibited significantly reduced serum E2 and P4 levels, down-regulated Bmal1, Clock and Per2 expression, as well as decreased phosphorylation levels of PI3K and Akt. But there was no significant difference of the total PI3K and Akt protein expression levels between the two groups. These results suggest that SD might affect the expression of the circadian clock genes in the hypothalamus and pituitary via PI3K/Akt pathway, and subsequently regulate the secretion of sex hormones in the pregnant rats, which hints the important roles of SD-induced changes of serum sex hormone levels in the pregnant rats.
ARNTL Transcription Factors/metabolism* ; Animals ; Circadian Clocks/physiology* ; Circadian Rhythm/genetics* ; Female ; Gene Expression Regulation/genetics* ; Gonadal Steroid Hormones/metabolism* ; Hypothalamus/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; Pituitary Gland/metabolism* ; Pregnancy ; Progesterone ; Proto-Oncogene Proteins c-akt/metabolism* ; Rats ; Rats, Wistar ; Signal Transduction ; Sleep Deprivation/metabolism*

Prostaglandin (PG) E plays critical roles during pregnancy and parturition. Emerging evidence indicates that human labour is an inflammatory event. We sought to investigate the effect of PGE on the output of proinflammatory cytokines in cultured human uterine smooth muscle cells (HUSMCs) from term pregnant women and elucidate the role of subtypes of PGE receptors (EP, EP, EP and EP). After drug treatment and/or transfection of each receptor siRNA, the concentrations of inflammatory secreting factors in HUSMCs culture medium were detected by the corresponding ELISA kits. The results showed that, PGE increased interleukin 6 (IL-6) and tumor necrosis factor alpha (TNFα) output, decreased chemokine (c-x-c motif) ligand 8 (CXCL8) output in a dose-dependent manner, but had no effect on IL-1β and chemokine (c-c motif) ligand 2 (CCL-2) secretion of HUSMCs. EP/EP agonist 17-phenyl-trinor-PGE stimulated IL-6 and TNFα whilst suppressing IL-1β and CXCL8 output. The effects of 17-phenyl-trinor-PGE on IL-1β and CXCL8 secretion were remained whereas its effect on IL-6 and TNFα output did not occur in the cells with EP knockdown. The stimulatory effects of 17-phenyl-trinor-PGE on IL-6 and TNFα were remained whereas the inhibitory effects of 17-phenyl-trinor-PGE on IL-1β secretion was blocked in the cells with EP knockdown. Either of EP and EP agonists stimulated IL-1β and TNFα output, which was reversed by EP and EP siRNA, respectively. The inhibitors of phospholipase C (PLC) and protein kinase C (PKC) blocked EP/EP modulation of TNFα and CXCL8 output. PI3K inhibitor LY294002 and P38 inhibitor SB202190 blocked 17-phenyl-trinor-PGE-induced IL-1β and IL-6 output, respectively. The inhibitors of adenylyl cyclase and PKA prevented EP and EP stimulation of IL-1β and TNFα output, whereas PLC and PKC inhibitors blocked EP- and EP-induced TNFα output but not IL-1β output. Our data suggest that PGE receptors exhibit different effects on the output of various cytokines in myometrium, which can subtly modulate the inflammatory microenvironment in myometrium during pregnancy.
Cells, Cultured ; Chromones ; pharmacology ; Cytokines ; metabolism ; Female ; Humans ; Imidazoles ; pharmacology ; Inflammation ; Morpholines ; pharmacology ; Myocytes, Smooth Muscle ; cytology ; Myometrium ; cytology ; Phosphatidylinositol 3-Kinases ; Pregnancy ; Pyridines ; pharmacology ; Receptors, Prostaglandin E ; physiology

Objective: To study the dose-response relationship between maternal thyroid hormone levels in the first twenty weeks of pregnancy and the infant physical and neuropsychological development. Methods: In this prospective cohort study, a total of 945 women and their children were included. Maternal serum samples during first half of the pregnancy were collected and analyzed for levels of thyroid hormones by using the electro-chemiluminescence immunoassay. Maternal social demographic information was collected by using the a self-administered questionnaire. Physical measurements of newborns and neuropsychological evaluation of infants were performed by doctors of maternal and child health care. Results: The differences in newborns' birth length and head circumference were significant among the newborns of mothers with different percentiles of maternal serum (thyroid-stimulating hormone, TSH) levels (P<0.05). Newborns with maternal TSH level ≥P(95) or <P(5) had significantly lower birth length and birth head circumference, compared with the newborns with maternal TSH level between P(25)-P(75) (P<0.05). Newborns' birth head circumferences showed an inverted U-shaped association with maternal serum TSH level (Y=33.940+0.003X-0.109X(2), F=4.685, P=0.009). The difference in mental development index (MDI) of the infants at 18-30 months were significant among the infants of mothers with different percentiles of maternal serum TSH level (P<0.05). Infants with maternal TSH level ≥P(90) showed lower MDI (6.39, 95%CI: 2.29-10.49, P=0.002) compared with the infants with maternal TSH level between P(25)-P(75). Infant's MDI at 18- 30 months also showed an inverted U-shaped association with maternal serum TSH level (Y=103.249-1.524X-0.939X(2), F=6.616, P=0.001). Conclusions: Maternal TSH level was associated with newborn's birth length, birth head circumference and infant's MDI at 18-30 months. Newborn's birth head circumference and infant's MDI at 18-30 months showed an inverted U-shaped association with maternal serum TSH-Z score.
Birth Weight/physiology* ; Child ; Child Development/physiology* ; China ; Female ; Fetal Blood/metabolism* ; Humans ; Infant ; Infant, Newborn/blood* ; Pregnancy ; Prenatal Exposure Delayed Effects/blood* ; Prospective Studies ; Thyroid Gland/physiology* ; Thyroid Hormones/metabolism* ; Thyrotropin/blood*

OBJECTIVEThe aim of this study was to investigate the ability of Pref-1+ adipocyte progenitor cells to mobilize into mesenteric lymph nodes (MLNs) and the dynamic expression of related chemokines during the development of rat MLNs.

METHODSImmunohistochemical analyses were used to detect the expression of Pref-1 and related chemokines. Transmission electron microscopy (TEM) was used to observe the changes in ultrastructure of MLNs.

RESULTSCells containing lipid droplets were found in all rat MLNs at embryonic day (E) 18.5, 2 and 6 weeks (w) after birth, and they were similar to fibroblastic reticular cells (FRCs) or follicular dendritic cells (FDCs) under TEM. Pref-1+ adipocyte progenitor cells were found in all MLNs. The expression level of Pref-1 was significantly increased at 2 w after birth and decreased at 6 w after birth. The tendency of Cxcl12 expression was consistent with that of Pref-1 and was positively correlated with the expression of Pref-1 (P < 0.01; r = 0.897). At E18.5, Cxcl13, and Ccr7 were significantly expressed in the MLN anlage, but the expression level of Ccl21 was low. The expression level of Cxcl13, Ccr7, and Ccl21 in MLN were significantly increased at 2 w after birth (P < 0.05), while the expression of Ccr7 and Ccl21 were significantly decreased at 6 w after birth (P < 0.05).

CONCLUSIONAdipocyte progenitor cells are involved in the rat MLNs development through differentiation into FRC and FDC. The expression of the relevant chemokines during the development of MLNs is dynamic and may be related to the maintenance of lymph nodes self-balance state.

Animals ; Chemokines ; genetics ; metabolism ; Female ; Gene Expression Regulation, Developmental ; physiology ; Intercellular Signaling Peptides and Proteins ; genetics ; metabolism ; Lymph Nodes ; embryology ; metabolism ; Membrane Proteins ; genetics ; metabolism ; Mesentery ; embryology ; Pregnancy ; Rats

Congenital heart disease (CHD) is the most common birth defect at present and has a complex etiology which involves the combined effect of genetic and environmental factors. Pregestational diabetes mellitus is significantly associated with the development of CHD, but the detailed mechanism remains unknown. This article reviews the research advances in the molecular mechanism of CHD caused by pregestational diabetes mellitus.
Animals ; Apoptosis ; Cell Movement ; Female ; Heart Defects, Congenital ; etiology ; Humans ; Neural Crest ; physiology ; Pregnancy ; Pregnancy in Diabetics ; Reactive Oxygen Species ; metabolism

BACKGROUNDGestational diabetes mellitus (GDM) is associated with both short- and long-term adverse health consequences for both the mother and her offspring. The aim was to study the prevalence and risk factors for GDM in Beijing.

METHODSThe study population consisted of 15,194 pregnant women attending prenatal care in 15 hospitals in Beijing, who delivered between June 20, 2013, and November 30, 2013, after 28 weeks of gestation. The participants were selected by cluster sampling from the 15 hospitals identified through random systematic sampling based on the number of deliveries in 2012. A questionnaire was designed to collect information.

RESULTSA total of 2987 (19.7%) women were diagnosed with GDM and 208 (1.4%) had diabetes in pregnancy (DIP). Age (OR: 1.053, 95% CI: 1.033-1.074, P < 0.01), family history of diabetes mellitus (OR: 1.481, 95% CI: 1.254-1.748, P < 0.01), prepregnancy body mass index (BMI) (OR: 1.481, 95% CI: 1.254-1.748, P < 0.01), BMI gain before 24 weeks (OR: 1.126, 95% CI: 1.075-1.800, P < 0.01), maternal birth weight (P < 0.01), and fasting plasma glucose at the first prenatal visit (P < 0.01) were identified as risk factors for GDM. In women with birth weight <3000 g, GDM rate was significantly higher.

CONCLUSIONSOne out of every five pregnant women in Beijing either had GDM or DIP and this constitutes a huge health burden for health services. Prepregnancy BMI and weight gain before 24th week are important modifiable risk factors for GDM. Ensuring birth weight above 3000 g may help reduce risk for future GDM among female offsprings.

Birth Weight ; physiology ; Body Mass Index ; Diabetes, Gestational ; metabolism ; Female ; Glucose Tolerance Test ; Humans ; Pregnancy ; Prevalence ; Risk Factors ; Weight Gain ; physiology

BACKGROUNDHyperglycemia is associated with adverse pregnancy outcomes. However, the relationships between them remain ambiguous. This study aimed to analyze the effect of different oral glucose tolerance test (OGTT) results on adverse perinatal outcomes.

METHODSThis retrospective cohort study included data from 15 hospitals in Beijing from June 20, 2013 to November 30, 2013. Women with gestational diabetes mellitus (GDM) were categorized according to the number and distribution of abnormal OGTT values, and the characteristics of adverse pregnancy outcomes were evaluated. Chi-square test and logistic regression analysis were used to determine the associations.

RESULTSIn total, 14,741 pregnant women were included in the study population, 2927 (19.86%) of whom had GDM. As the number of hyperglycemic values in the OGTT increased, the risk of cesarean delivery, preterm births, large-for-gestational age (LGA), macrosomia, and neonatal complications significantly increased. Fasting hyperglycemia had clear associations with macrosomia (odds ratios [OR s]:1.84, 95% confidence intervals [CI s]: 1.39-2.42,P < 0.001), LGA (OR: 1.70, 95% CI: 1.29-2.25,P < 0.001), and cesarean delivery (OR: 1.33, 95% CI: 1.15-1.55,P < 0.001). The associations were stronger as fasting glucose increased. GDM diagnosed by hyperglycemia at OGTT-2 h was more likely to lead to preterm birth (OR: 1.50, 95% CI: 1.11-2.03,P < 0.01).

CONCLUSIONSVarious characteristics of OGTTs are associated with different adverse outcomes. A careful reconsideration of GDM with hierarchical and individualized management according to OGTT characteristics is needed.

Birth Weight ; physiology ; Blood Glucose ; metabolism ; Body Mass Index ; Cesarean Section ; Chi-Square Distribution ; Diabetes, Gestational ; blood ; physiopathology ; Female ; Fetal Macrosomia ; blood ; physiopathology ; Glucose Tolerance Test ; methods ; Humans ; Pregnancy ; Pregnancy Complications ; Pregnancy Outcome ; Premature Birth ; blood ; physiopathology ; Retrospective Studies

BACKGROUNDAt present, a diagnostic tool with high specificity for impaired endometrial receptivity, which may lead to implantation failure, remains to be developed. We aimed to assess the different endometrial microRNA (miRNA) signatures for impaired endometrial receptivity by microarray analysis.

METHODSA total of 12 repeated implantation failure (RIF) patients and 10 infertile patients, who conceived and delivered after one embryo transfer attempt, were recruited as RIF and control groups, respectively. Endometrial specimens from the window of implantation (WOI) were collected from these two groups. MiRNA microarray was conducted on seven and five samples from the RIF and control groups, respectively. Comparative, functional, and network analyses were performed for the microarray results. Quantitative real-time polymerase chain reaction (PCR) was performed on other samples to validate the expression of specific miRNAs.

RESULTSCompared with those in the control group, the expression levels of 105 miRNAs in the RIF group were found to be significantly up- or down-regulated (at least 2-fold) by microarray analysis. The most relevant miRNA functional sets of these dysregulated miRNAs were miR-30 family, human embryonic stem cell regulation, epithelial-mesenchymal transition, and miRNA tumor suppressors by tool for annotations of microRNA analysis. Network regulatory analysis found 176 miRNA-mRNA interactions, and the top 3 core miRNAs were has-miR-4668-5p, has-miR-429, and has-miR-5088. Expression levels of the 18 selected miRNAs in new samples by real-time PCR were found to be regulated with the same trend, as the result of microarray analysis.

CONCLUSIONSThere is a significant different expression of certain miRNAs in the WOI endometrium for RIF patients. These miRNAs may contribute to impaired endometrial receptivity.

Adult ; Embryo Implantation ; genetics ; physiology ; Endometrium ; metabolism ; Female ; Humans ; Infertility, Female ; genetics ; MicroRNAs ; genetics ; Microarray Analysis ; Pregnancy ; Real-Time Polymerase Chain Reaction

OBJECTIVETo provide a comprehensive literature review on roles of coagulation factor XIII (FXIII) in coagulation, wound healing, neoplasm, bone metabolism, and pregnancy.

DATA SOURCESAll articles in PubMed with key words "Coagulation factor XIII", "wound", "leukemia", "tumor", "bone," and "pregnancy" with published date from 2001 to 2016 were included in the study. Frequently cited publications before 2000 were also included.

STUDY SELECTIONWe reviewed the role of FXIII in biologic processes as documented in clinical, animal, and in vitro studies.

RESULTSFXIII, a member of the transglutaminase (TG) family, plays key roles in various biological processes. Besides its well-known function in coagulation, the cross-linking of small molecules catalyzed by FXIII has been found in studies to help promote wound healing, improve bone metabolism, and prevent miscarriages. The study has also shown that FXIII concentration level differs in the blood of patients with leukemia and solid tumors and offers promises as a diagnostic indicator.

CONCLUSIONSFXIII has many more biologic functions besides being known as coagulation factor. The TG activity of FXIII contributes to several processes, including wound healing, bone extracellular matrix stabilization, and the interaction between embryo and decidua of uterus. Further research is needed to elucidate the link between FXIII and leukemia and solid tumors.

Abortion, Spontaneous ; metabolism ; prevention & control ; Animals ; Blood Coagulation ; physiology ; Factor XIII ; metabolism ; physiology ; Female ; Humans ; Leukemia ; metabolism ; Pregnancy ; Wound Healing ; physiology