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Trophoblast cell syncytialization is essential for placental and fetal development. Abnormal trophoblast cell fusion leads to pregnancy pathologies, such as preeclampsia (PE), intrauterine growth restriction (IUGR), and miscarriage. 27-hydroxycholesterol (27-OHC) is the most abundant oxysterol in human peripheral blood synthesized by sterol 27-hydroxylase (CYP27A1) and is considered a critical mediator between hypercholesterolemia and a variety of related disorders. Gestational hypercholesterolemia was associated with spontaneous preterm delivery and low birth weight (LBW) in term infants, yet the mechanism is unclear. In this study, two trophoblast cell models and CD-1 mice were used to evaluate the effects of 27-OHC on trophoblast fusion during placenta development. Two different kinds of trophoblast cells received a dosage of 2.5, 5, or 10 uM 27-OHC. Three groups of pregnant mice were randomly assigned: control, full treatment (E0.5-E17.5), or late treatment (E13.5-E17.5). All mice received daily intraperitoneal injections of saline (control group) and 27-OHC (treatment group; 5.5 mg/kg). In vitro experiments, we found that 27-OHC inhibited trophoblast cell fusion in primary human trophoblasts (PHT) and forskolin (FSK)-induced BeWo cells. 27-OHC up-regulated the expression of the PI3K/AKT/mTOR signaling pathway-related proteins. Moreover, the PI3K inhibitor LY294002 rescued the inhibitory effect of 27-OHC. Inhibition of trophoblast cell fusion by 27-OHC was also observed in CD-1 mice. Furthermore, fetal weight and placental efficiency decreased and fetal blood vessel development was inhibited in pregnant mice treated with 27-OHC. This study was the first to prove that 27-OHC inhibits trophoblast cell fusion by Activating PI3K/AKT/mTOR signaling pathway. This study reveals a novel mechanism by which dyslipidemia during pregnancy results in adverse pregnancy outcomes. [ABSTRACT FROM AUTHOR]

The study of placental lipid metabolism in uncomplicated pregnancies has not been developed in the literature to date. Its importance lies in expanding the knowledge of placental function to enable comparison with pathological pregnancies in future research. The aim of the present study was to compare the lipid metabolic activity and storage of the maternal and fetal sides of the placenta in healthy pregnancies. Moreover, we compare singleton vs. twin pregnancies to determine if placental metabolic needs differ. We analyzed placental explants from uncomplicated pregnancies, 20 from singleton and 8 from bichorial-biamniotic twin pregnancies (n = 28). Six cotyledon fragments were collected from each placenta at different distances from the umbilical cord, three close to the chorionic plate (hereinafter, we will refer to them as "fetal side") and another three close to the anchoring villi into the decidua basalis (referred to as "maternal side"). The samples were analyzed for quantitative assay placental fatty acid oxidation (FAO) and esterification (FAE) activities and triglyceride levels. The location of lipid storage in the chorionic villi was assessed by Oil red-O staining. Placental fatty acid oxidation did not show differences when comparing the maternal and fetal sides of the placenta or between single and twin pregnancies. When comparing placental sides, FAE was increased twofold in the maternal side compared to the fetal side of the placenta (P = 0.013). The tendency for lipogenesis in the placenta was exemplified by the FAE/FAO ratio, which was a 37.1% higher on the maternal side (P = 0.019). Despite this, triglyceride levels were five times higher in the fetal side than in the maternal one (P = 0.024). When analyzing singleton vs. twins, FAE was superior in the fetal side in multiple pregnancies (× 2.6, P = 0.007) and the FAE/FAO ratio was significantly higher in twins than in singleton pregnancies, on both sides of the placenta. Despite this finding, triglyceride levels were similar in twin and singleton pregnancies. Comparing the placentas of twins in the same pregnancy, there were no differences in lipid metabolism (FAO or FAE) or placental triglyceride levels between the two co-twins. Using Oil red-O staining, lipid storage in chorionic villi was found to be located on the syncytiotrophoblast cells and not in the connecting axis. The maternal side of the placenta is more active in the esterification of fatty acids, while the storage of neutral lipids concentrates on the fetal side. Moreover, multiple gestations have increased esterification without changes in the concentration of placental triglycerides, probably due to a higher transfer to the fetal circulation in response to the greater energy demand from twin fetuses. [ABSTRACT FROM AUTHOR]

Objective: To explore the therapeutic effect and the possible working mechanism in using Chinese herbal medicine (CHM) for supplementing Kidney and Qi, and activating blood circulation in treating intrauterine growth retardation of fetus (IUGR). Methods: Fifty-five cases of IUGR were divided into two groups, 30 cases in the CHM group treated with CHM and the 25 in the control group treated with amino acids. The effect of CHM treatment was observed and compared with that of the control group, normal pregnancy group and non-treated IUGR group. Results: Body weight of the newborns in the CHM was markedly higher than that in the control group. Not only the maternal fundal height (FH) and the abdominal circumference (AC), but also the fetal growth parameters, including biparietal diameter, head circumference (HC), and femur length (FL) in the CHM group increased much faster than those in the control group. After CHM treatment, the maternal serum levels of estriol (E) and human placental lactogen (hPL) approached to those in the normal pregnancy group, but the control group, in comparison with the normal pregnancy group, was significantly different. The umbilical venous plasma concentration of essential amino acids in both treated groups improved, but the improvement in the CHM group was more significant than that in the control group. No apparent adverse effect of CHM was observed in either mother or fetus. Conclusion: CHM for supplementing Kidney and Qi and activating blood circulation was more effective in improving placental function and enhancing amino acid transportation than amino acid. [ABSTRACT FROM AUTHOR]

Serum aminopeptidase A (AAP) activity was measured in normal pregnancy and pre-eclampsia. The AAP activity in normal pregnancy increased progressively with advancing gestation, reaching the highest value at the end of pregnancy. The AAP activity in pregnancy complicated by pre-eclampsia was lower than in normal pregnancy. [ABSTRACT FROM AUTHOR]

Postterm and growth-retarded fetuses share a common problem which can be characterized by a discrepancy between the supply of oxygen and nutrients to, and the demand of the fetus. But, this "insufficient" placental exchange function may also extend to and affect its thermal homeostasis; e.g. when the capacity of convective (placenta) pathways is shifted towards conductive (surface) pathways for heat loss. Therefore, fetal scalp heat flux measurements, where heat serves as an intrinsic tracer for metabolic activity and placental exchange function, promised a new kind of information. In 81 pregnant women during labor we measured fetal scalp heat flux by means of an heat flux transducer attached to the fetal head and after the cervix had dilated to 3 cm. In the healthy fetuses we found a positive linear relationship between scalp heat flux and different anthropometric variables such as body length (r = 0.432, n = 65, P less than 0.01), head circumference and gestational age. In comparison, postmature and growth-retarded fetuses showed higher heat flux values than appropriately grown fetuses of the same length head size and gestational age. Moreover, in those fetuses scalp heat flux decreased by approximately 4 watt/m2 during the second stage and differed in this regard from the control group who showed stable values during labor and delivery. We conclude that scalp heat flux measurements may indicate disturbances of placental exchange before acute hypoxia occurs. [ABSTRACT FROM AUTHOR]