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

Endocrine hormones are important factors in maintaining pregnancy as well as initiation of parturition. Progesterone is the major hormone maintaining myometrium quiescence, while glucocorticoids, prostaglandins and estrogen are among the major hormones involved in the initiation of parturition. Therefore progesterone withdrawal at the end of pregnancy is the prerequisite for the initiation of parturition. However, unlike most of the other species of mammals that the withdrawal of progesterone is achieved via reduction of progesterone synthesis or increased conversion of progesterone to estrogen, some mammals including the primates maintain high progesterone level throughout gestation and even during parturition. Accumulating lines of evidence indicate that the withdrawal of progesterone in human being is attained via the changes of the expression ratio of progesterone receptor subtypes and the changes of co-activators required for the activation of transcriptional activity of progesterone receptor. Here we reviewed the three major mechanisms, namely luteolysis, upregulation of placental P450c17 hydroxylase and changes of progesterone receptor functions, underlying progesterone withdrawal in late pregnancy in mammals.
Animals ; Female ; Humans ; Luteolysis ; physiology ; Parturition ; metabolism ; physiology ; Pregnancy ; Pregnancy Trimester, Third ; metabolism ; physiology ; Progesterone ; metabolism ; Receptors, Progesterone ; metabolism ; physiology ; Species Specificity ; Steroid 17-alpha-Hydroxylase ; metabolism

Amnion ; metabolism ; physiology ; Female ; Hepatectomy ; Humans ; Liver Regeneration ; physiology ; Pregnancy ; Wound Healing ; physiology

Animals ; Antimicrobial Cationic Peptides ; physiology ; Carrier Proteins ; physiology ; Cation Transport Proteins ; physiology ; Ceruloplasmin ; physiology ; Female ; Ferritins ; physiology ; Hemochromatosis Protein ; Hepcidins ; Histocompatibility Antigens Class I ; physiology ; Humans ; Iron ; metabolism ; Iron-Regulatory Proteins ; physiology ; Membrane Proteins ; physiology ; Placenta ; metabolism ; Pregnancy ; Transferrin ; physiology

The placenta is an essential organ that synthesizes several growth and angiogenic factors for its own growth as well as fetal development. It is known that the placenta growth factor (PlGF)is a member of the vascular endothelial growth factor family and is critical for placental growth and fetal development. However, there is little information regarding the expression pattern and cellular localization of PlGF mRNA in rat placenta during pregnancy. The aim of this study was to define the distribution of PlGF mRNA in rat placenta at various gestations. RT-PCR analysis showed that the expression level of PlGF mRNA increased as gestation advanced. Using in situ hybridization histochemistry, positive cells of PlGF mRNA were detected in chorionic villi. PlGF mRNA was expressed in the trophoblast cells and stroma cells surrounding the blood vessels within chorionic villi on day 13 and 15. Also, positive signals of PlGF mRNA were strongly detected in stroma cells of chorionic villi on day 17, 19, and 21. In particular, the density and number of positive signals of PlGF mRNA was significantly increased as gestation advanced. The expression pattern of PlGF mRNA in rat placenta during pregnancy demonstrates that PlGF plays a functional role for placental growth and fetal development during mid-late pregnancy.
Animals ; Female ; Gene Expression Regulation/physiology ; Placenta/*metabolism ; Pregnancy ; Pregnancy Proteins/*metabolism ; RNA, Messenger/*metabolism ; Rats ; Rats, Sprague-Dawley ; Tissue Distribution/physiology

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

Activin is a member of the transforming growth factor-beta (TGF-beta) superfamily that result from the assembly of disulphide-linked betaA and betaB subunits. Activin receptors are transmembrane proteins and activin fulfils the biological function through the signal transduction of the receptor system. In recent years, many studies have suggested that activins have wide biological activities. It is the basic medium in regulating histiocytic function and plays a role in maintaining the normal function of cells. Moreover, abnormal expression of activin in the tissues of many gynecologic and obstetric diseases, such as epithelial ovarian tumor, endometrial carcinoma, pre-eclampsia, polycystic ovary syndrome, endometriosis and so on affects the development of these diseases.
Activin Receptors ; metabolism ; physiology ; Activins ; physiology ; Animals ; Endometrial Neoplasms ; metabolism ; Endometriosis ; metabolism ; Female ; Humans ; Ovarian Neoplasms ; metabolism ; Pre-Eclampsia ; metabolism ; Pregnancy

OBJECTIVETo study the changes of MAPK and Akt signaling pathways in hearts and placentas of aborted fetuses with congenital heart disease (CHD), and investigate their roles in the pathogenesis of CHD.

METHODSTen aborted fetuses with severe CHD (CHD group) and 7 gestational age-matched non-cardiac malformation aborted fetuses (control group) were enrolled. Western blot analysis was undertaken to assess the expression of p38, p38alpha, p-p38, MEF2, ERK, p-ERK, Akt, p-Akt(Ser473) and p-Akt(Thr308) in left ventricles and placentas of the fetuses, while semi-quantitative reverse transcription polymerase chain reaction analysis was used to detect the expression of p38alpha isoforms mRNA in hearts.

RESULTSCompared with the heart samples of the control group, the protein expression levels of p38 and its alpha isoform in 4 cases, p-p38 in 6 cases, MEF2 in 2 cases, p-ERK in 8 cases, Akt in 4 cases, p-Akt(Ser473) and p-Akt(Thr308) in 8 cases decreased, while the protein expression levels of p-p38 in 2 cases and p-Akt(Thr308) in 1 case increased. P-p38 protein level in 3 cases and p-ERK protein level in 2 cases decreased in placentas compared with the control group. The changes of protein expression of MAPK and Akt signaling pathway in hearts were not consistent with those in placentas in the CHD group. The expression of p38alpha isoform2 mRNA showed descent tendency in 4 heart samples with CHD, while the expression of other three p38alpha isoforms mRNA was reduced in only 1 sample compared with the control group.

CONCLUSIONSDysfunction of MAPK and Akt signaling pathways is tissue-specific in aborted fetuses with CHD. The perturbed two signaling pathways in hearts may contribute to the pathogenesis of human CHD.

Female ; Fetus ; metabolism ; Heart Defects, Congenital ; metabolism ; Humans ; MAP Kinase Signaling System ; physiology ; Myocardium ; metabolism ; Phosphatidylinositol 3-Kinases ; physiology ; Placenta ; metabolism ; Pregnancy ; Proto-Oncogene Proteins c-akt ; physiology ; Signal Transduction ; physiology ; p38 Mitogen-Activated Protein Kinases ; physiology

OBJECTIVE: To examine the association among malondialdehyde (MDA), superoxide dismutase (SOD) and incidence of apoptosis of granulosa cells in follicular fluid with the outcome of in vitro fertilization-embryo transfer (IVF-ET). METHODS: We recruited 51 women undergoing an IVF-ET programme for tubal factor infertility. The women with endometriosis or endocrine diseases and those with male factor infertility were excluded. All the 51 patients underwent a long gonadotropin-releasing hormone (GnRH) agonist protocol for pituitary downregulation followed by controlled ovarian hyperstimulation with rFSH. Granulosa cells were isolated from all aspirated follicular fluid using gradient centrifugation at oocyte retrieval. The level of MDA and the activity of the SOD were measured by the thiobarbituric acid(TBA)and the chemiluminescence method, respectively. The apoptosis was studied by flow cytometry using propidium iodide. RESULTS: Twenty-six out of the 51 patients (51.0%) were pregnant after IVF-ET. Non-pregnant patients showed significantly higher MDA level [(1.7±0.72) nmol/(g × prot) vs. (1.1±0.56) nmol/(g × prot), P<0.05)], higher incidence of apoptosis (24.8%±6.57% vs.19.0%±5.59%, P<0.05) and lower SOD level [(3.5±1.08)×10(3)NU/(g × prot) vs. (4.4±0.99)×10(3)NU/(g × prot), P<0.05)] in the granulose cells and lower good-embryo rate (54.9±20.22% vs. 65.9±16.16%, P<0.05) compared with the pregnant patients. No correlation was detected among SOD and the number of retrieved oocytes, oocyte maturity, embryo quality, fertilization, or cleavage. A significant negative correlation was detected between MDA and fertilization rate (r=-0.425, P=0.002). No significant correlation was detected between MDA and age, the number of retrieved oocytes, oocyte maturity, cleavage, or good-embryo rate. A significant negative correlation was detected between the incidence of apoptosis and the number of retrieved oocytes (r=-0.286, P=0.042), mature oocytes (r=-0.330, P=0.020) and good-embryo rate (r=-0.311, P=0.026). There was significant negative correlation between MDA and SOD levels (r=-0.471, P<0.001); and significant positive correlation between MDA level and incidence of apoptosis (r=0.475, P<0.001). CONCLUSION Oxidative stress may induce apoptosis in granulose cells and subsequently lower oocyte quality and lead to poor outcome of IVF-ET.
Adult ; Apoptosis ; physiology ; Embryo Transfer ; Female ; Fertilization in Vitro ; Granulosa Cells ; metabolism ; pathology ; Humans ; Malondialdehyde ; metabolism ; Ovary ; cytology ; metabolism ; Oxidative Stress ; Pregnancy ; Pregnancy Rate ; Superoxide Dismutase ; metabolism ; Treatment Outcome

By the method of single preimplantation embryos differential display polymerase chain reaction (SPEDDRT-PCR), 25 reprogramming cDNA fragments were obtained from single 2-cell, 8-cell embryos and blastula. After cloning and sequencing, five of them were identified by reverse-Northern and characterized with stage-specific expression during reconstructed embryo development. This results will help to isolate full length reprogramming genes and study their function during embryonic development.
Animals ; Blastocyst ; metabolism ; physiology ; Blotting, Northern ; Embryo, Mammalian ; metabolism ; Embryonic Development ; genetics ; physiology ; Female ; Gene Expression Regulation, Developmental ; genetics ; physiology ; Polymerase Chain Reaction ; Pregnancy ; Rabbits