LncRNA uc003fir promotes CCL5 expression and negatively affects proliferation and migration of trophoblast cells in preeclampsia.

OBJECTIVE: To evaluate the role of lncRNA uc003fir in the progression and development of preeclampsia (PE). DESIGN: Paired test using placental tissue collected from PE women and normally pregnant women. SETTING: First Hospital of Soochow University, Suzhou, China. POPULATION: 38 women with PE versus 42 normally pregnant women matched maternal and gestational age with the same-size ratio. METHODS: Placental samples were analyzed using a human lncRNA microarray, and then the lncRNA uc003fir was validated by q-PCR. MTT, cell scratch, and transwell invasion assays were performed regarding biological functions. MAIN OUTCOME MEASURES: LncRNA uc003fir promoted CCL5 expression and negatively affected the proliferation and migration of HTR-8/SVneo cells. RESULTS: LncRNA uc003fir was significantly over-expressed in PE compared to the control. The chemokine CCL5 was directly regulated by lncRNA uc003fir through transfection of over-expression plasmid of lncRNA uc003fir in HTR-8/SVneo cells, accompanied by up-regulation of lncRNA uc003fir in preeclamptic placental vessels and vessel-free tissue. In detecting the biological function of lncRNA uc003fir on trophoblast cells, over-expression of lncRNA uc003fir increased proliferation, migration, and invasion of HTR-8/SVneo cells, whereas the knockdown inhibited. CONCLUSION: LncRNA uc003fir was dysregulated in placental tissue in PE. LncRNA uc003fir regulated CCL5 directly, which may mediate the recruitment of pro-inflammatory cytokines released from monocytes and other leukocytes. Additionally, lncRNA uc003fir may interact with microRNAs to affect the invasion of trophoblast cells into myometrium, indicating that lncRNA uc003fir could be considered as a target in PE.

Effect of response to phenylephrine-mediatedsignal pathway in renal arteries of offspring rats inducedby maternal high-salt diet / 中国药理学通报

Aim To study the effect of high salt diet during pregnancy on the development of renal vessels in offspring rats and its mechanism.Methods Natural pregnant Sprague-Dawley rats were randomly divided into high-salt group and control group.The pregnant rats in the high-salt group were given high-salt diet of 8% NaCl content , while the control group normal diet with 1% NaCl content.In both groups, pregnant rats were given normal drinking water.After delivery, all mothers returned to normal diet and all neonatal rats were breast-fed until one month old.The adult male off springs were used as experimental animals.The vessel tone of renal interlobar arteries and electrophysiological behavior of single vascular smooth muscle cells (VSMCs) were detected respectively.Results The contractile response of renal arteries to phenylephrine(Phe) in high-salt group was stronger than that in the control group(P0.05).Conclusions High-salt diet during pregnancy could increase the sensitivity of renal interlobar arterial contractile response to Phe in adult male offsprings, which is associated with PKC-mediated BK channels pathway.Maternal high-salt diet during pregnancy may increase the risk of renal vascular diseases in adult offsprings.

Effects of prenatal hypoxia on vascular functions of fetal rats / 中华围产医学杂志

Objective To explore the effects and mechanisms of prenatal hypoxia on vasomotor functions of fetal rats.Methods Sixteen pregnant Sprague-Dawley rats were randomly divided into two groups:control and hypoxia groups (eight in each group).Rats in the hypoxia group were provided with 10.5％ of oxygen from gestation day 5 to 21,while those in the control group were exposed to normoxic condition.Fetuses were removed from the pregnant rats by cesarean section on gestational day 21.Fetal body weight,blood gas and electrolyte levels were measured.Thoracic aorta rings were separated from fetal rats and used in different vascular function tests.Effects of hypoxia during pregnancy on angiotensin Ⅱ (Ang Ⅱ)-mediated vasoconstrictions and acetylcholine (Ach)-mediated vasodilatations in fetal thoracic aortas were measured.Changes in vasomotor functions were observed after both endothelial nitric oxide synthase (eNOS) inhibitor NG-nitro-L-arginine methyl ester (L-Name) and L-type calcium channel (LTCC) inhibitor nifedipine were administered.T-test and two-way analysis of variance were used for statistical analysis.Results (1) Compared with the control group,fetal body weight [(4.40±0.23) vs (3.33±0.42) g,t=2.871],blood partial pressure of oxygen [(50.64±2.17) vs (42.50-±-2.32) mmHg (1 mmHg=0.133 kPa),t=-2.618] and blood oxygen saturation [(58.95±1.97)％ vs (47.73±2.24)％,t=3.564] in the hypoxia group were significantly reduced (all P＜0.05).(2) Compared with the control group,Ang Ⅱ-mediated vasoconstrictions increased,but Ach-mediated vasodilatations in fetal thoracic aortas decreased in the hypoxia group (both P＜0.05).L Name induced stronger Ang Ⅱ-mediated contractions in thoracic aortas in the control group than that in the hypoxia group (P＜0.05).However,nifedipine decreased Ang Ⅱ-induced contractions,especially in the hypoxia group (P＜0.05).Conclusions Maternal hypoxia during pregnancy not only affects the growth and development of fetuses but also changes their blood vessel functions,which may be related to the change of LTCC and the impairment of eNOS.

Effects of β-estradiol on vasoconstriction in human umbilical artery and vein / 中华围产医学杂志

Objective To determine the effects of β-estradiol on vasoconstriction in human umbilical artery and vein and its potential mechanisms.Methods Human umbilical cord samples were obtained from 96 term neonates of healthy singleton pregnant women born in the First Hospital of Soochow University between December 2013 and June 2015 (multiple pregnancy,pregnancy complications,cesarean delivery and low birth weight were excluded).Human umbilical arteries and veins were isolated and suspended in 37 2 organ baths containing 5 ml Krebs solution and exposed to β-estradiol followed by phenylephrine (PE) for vasoconstriction test.The subjects were divided into β-estradiol group and control group according to the presence or absence of β-estradiol incubation.To determine the effects and the possible underlying mechanisms of β-estradiol on PE-induced vasoconstriction,human umbilical artery and vein rings were pretreated with N ω-nitro-L-arginine (L-NMMA,nitric oxide synthesis inhibitor),fulvestrant (ICI182780,estradiol receptor antagonist),indomethacin (prostaglandin synthesis blocker),and removal of endothelium,then incubated with β-estradiol for 60 min followed by PE,and the concentration-response curves to PE were recorded.The concentrationresponse curves to phorbol 12,13-dibutyrate (PDBU,protein kinase C agonist) in Krebs solution in the presence or absence of β-estradiol were also obtained.Nonlinear regression and fitting curve were performed,and the two-sample ANOVA was used for analysis.Results (1) β-estradiol suppressed PE-induced vasoconstriction of human umbilical vein and artery.In human umbilical vein and artery of the control group,the maximum contraction intensity induced by PE was (59.17± 5.98)％ and (43.35± 5.02)％ of that induced by potassium chloride,respectively.The maximum contraction induced by PE in β-estradiol group was (5.87± 1.32)％and (4.52±1.22)％ of that induced by potassium chloride.(2) In both groups,incubation with L-NMMA or endothelium removal enhanced the vasoconstriction of human umbilical artery and vein,indicating that the inhibitory effect of β-estradiol was not influenced by the endothelium.(3) The suppression of β-estradiol on PE-induced vasoconstriction in human umbilical artery and vein was not significantly decreased by estrogen receptor antagonist.(4) β-estradiol did not affect human umbilical artery and vein vasoconstriction induced by PDBU.(5) In the control group,incubation with indomethacin did not affect human umbilical artery and vein vasoconstriction induced by PE.In the β-estradiol group,indomethacin significantly enhanced the contraction response induced by PE,suggesting that prostacycline synthesis was partly involved in β-estradiol-suppressed contractility in human umbilical artery and vein.The contractile response induced by phenylephrine was still lower in the β-estradiol group than in the control group,which was induced by indomethacin.Conclusions (1) β-estradiol can suppress vasoconstriction in human umbilical artery and vein,which is not dependent on endothelium and estrogen receptors,or protein kinase C activity,(2) Prostacycline synthesis is partly involved in β-estradiol-suppressed vasoconstriction in human umbilical artery and vein.

Fetal and offspring arrhythmia following exposure to nicotine during pregnancy.

Although recent studies have demonstrated prenatal nicotine can increase cardiovascular risk in the offspring, it is unknown whether exposure to nicotine during pregnancy also may be a risk for development of arrhythmia in the offspring. In addition, in previous studies of fetal arrhythmia affected by smoking, only two patterns, bradycardia and tachycardia, were observed. The present study examined acute effects of maternal nicotine on the fetal arrhythmia in utero, and chronic influence on offspring arrhythmia at adult stage following prenatal exposure to nicotine. Nicotine was administered to pregnant ewes and rats. In the fetal sheep, intravenous nicotine not only induced changes of fetal heart rate, but also caused cardiac cycle irregularity, single and multiple dropped cardiac cycles. Although maternal nicotine had no influence on fetal blood pH, lactic acid, hemocrit, Na(+), K(+) levels and plasma osmolality, fetal blood PO(2) levels were significantly decreased following maternal nicotine in ewes. In offspring rats at 4-5 months after birth, prenatal exposure to nicotine significantly increased heart rate and premature ventricular contraction in restraint stress. In addition, arrhythmias induced by injection of nicotine were higher in the offspring prenatal exposure to nicotine in utero. The results provide new evidence that exposure to nicotine in pregnancy can cause fetal arrhythmia in various patterns besides tachycardia and bradycardia, the possible mechanisms for nicotine-induced fetal arrhythmia included in utero hypoxia. Importantly, following exposure to nicotine significantly increased risk of arrhythmia in the adult offspring. The finding offers new insight for development of cardiac rhythm problems in fetal origins.

Effect of acupuncture on pubertal development of rats and rabbits at different developmental stages.

Physiological and endocrine studies on sexual development in animals and effects of acupuncture on sexual development are limited. Therefore, we investigated the effect of electro-acupuncture (EA) on the arcuate nucleus (Arc) and release of gonadotropin-releasing hormone (GnRH) in animals at different developmental stages. In Experiment 1, EA stimulation (30 Hz) was performed for 30 min per day in EA group of rabbits for 48 days, while the control group (mature rabbits) was not given EA. Arc discharges in those two groups were measured after the 48-day treatment. Arc discharge was also measured in the pre-pubertal group (as control) without EA treatment. Then, all three groups were treated with transient EA for 30 min and Arc discharges were determined again. In Experiment 2, EA (3 Hz) at the same acupoints or non-acupoints as that in the rabbits was performed for 20 min per day in different developmental group of Sprague-Dawley rats for 10 days. GnRH mRNA expression in the hypothalamus of rats was determined using RT-PCR and real-time PCR. The serum sexual hormone, sperm count, and body weight was measured. The results showed that the Arc discharge (P<0.01), testosterone (T) (P<0.01) and sperm count (P<0.01) in male rabbits were reduced by repeated EA. However, the body weight of rabbits was not changed after EA compared to the control in Experiment 1. In Experiment 2, GnRH mRNA expression in rats of the early pubertal group (EPG) and adult group (AG) were significantly depressed after repeated EA at acupoints (P<0.01). The sexual hormones were negatively influenced by repeated EA during puberty. Sperm count was reduced significantly after repeated EA at time of puberty (P<0.01). Repeated EA did not influence body weight of rats (P>0.01) and structures of the gonadial tissues during development. The results suggested that repeated EA is a good option that can be considered for regulating the function of the hypothalamus-pituitary-gonad (HPG) axis during puberty.