Circulating levels of pregnanolone isomers during the third trimester of human pregnancy

This study addresses the question of whether changes in the biosynthesis and metabolism of neuroactive pregnanolone isomers (PIs) might participate in the timing of parturition in humans. The time profiles of unconjugated allopregnanolone (3-hydroxy-5-pregnan-20-one, P35), pregnanolone (3-hydroxy-5β-pregnan-20-one, P35β), isopregnanolone (3β-hydroxy-5-pregnan-20-one, P3β5) and epipregnanolone (3β-hydroxy-5β-pregnan-20-one, P3β5β), pregnenolone, their polar conjugates, progesterone, 5-dihydroprogesterone (P5), and 5β-dihydroprogesterone (P5β) were monitored in the plasma of 30 healthy women during the third trimester of pregnancy, at 1-week intervals from the 30th week of gestation using GC–MS. Changes in the steroid levels were evaluated by two-way ANOVA with gestational age and subject as independent factors. The mean concentrations of free PIs ranged from 2 to 50 nmol/L, while the mean levels of their polar conjugates were 40–100× higher. The ratio of 5-PIs to progesterone significantly but inconspicuously culminated in the 35th week. The decelerating biosynthesis of free 5β-PIs from the 31st week and their escalating sulfation was found from the 30th week. The changes were particularly evident in the second most abundant PI pregnanolone that may, like the allopregnanolone, sustain the pregnancy via attenuation of hypothalamic GABA_A-receptors and prevent uterine contractility via binding to nuclear pregnane X receptor.     

妊娠晚期生殖道感染与妊娠结局的相关性分析

目的探讨妊娠晚期几种常见的生殖道病原微生物感染与妊娠结局的相关性。方法选取2013年1月至2015年4月新疆医科大学第二附属医院收治的妊娠晚期生殖道病原微生物感染患者633例作为观察组,同时随机选取同期病原体检测阴性者413例作为对照组,比较两组不良妊娠结局的发生情况。结果经过临床实验室检查,观察组中病原微生物培养情况分布以支原体感染491例(46.94%)、假丝酵母菌感染195例(18.64%)两种较为多见,观察组中支原体感染者胎膜早破、产褥感染、新生儿感染(χ2=65.44,P0.05);衣原体感染者早产、产褥感染(χ2=72.87,P0.05);滴虫感染者胎膜早破、产褥感染(χ2=24.20,P0.05);假丝酵母菌感染者早产、胎膜早破、产褥感染、胎儿窘迫、新生儿感染率(χ2=71.76,P0.05)明显高于对照组,差异有统计学意义。剖宫产率及新生儿窒息率的比较差异无统计学意义(χ2=1.04,P0.05)。而多重与单一病原体感染比较,除早产外其余妊娠结局差异无统计学意义(χ2=73.08,P0.05)。结论妊娠晚期生殖道病原微生物感染,会增加不良妊娠结局的发生率,应引起围产妇及临床医师的重视,适时进行干预减少不良结局的发生。     

Ultrastructure of the chorionic villus of the human placenta of the second and third trimester pregnancy.

38 human placentae of the 14th week of normal gestation were studied ultrastructurally. The thickness of the syncytial layer of villi varied markedly, and the syncytial cytoplasm showed marked vacuolization, which increased in the course of pregnancy in association with intensification of processes of resorption and absorption and hormonal function of the syncytium. Toward the end of the 2nd and at the beginning of the 3rd trimester of pregnancy, hypertrophic cytotrophoblastic cells appeared, whose ultrastructural character indicated functional stimulation. This observation contradicts the widely held view that cytotrophoblastic cells undergo gradual reduction in the course of pregnancy.     

孕晚期肠道菌群与孕妇血糖血脂的临床相关性

[背景]孕期体重增长不当与孕妇血糖血脂水平紊乱密切相关,而血糖血脂水平与母胎代谢性疾病的发生密切相关.肠道菌群协调肠道细胞吸收营养物质,可能与母婴糖脂代谢疾病的发生具有密切关系.[目的]观察孕期增重不同的孕妇肠道菌群生物多样性、丰富度与功能间差异,探讨孕晚期肠道菌群与孕妇血糖血脂的相关性.[方法]收集34例孕晚期孕妇粪...     

Salivary unconjugated estriol levels in normal third trimester pregnancy - direct correlation with serum levels

A radioimmunoassay for salivary unconjugated estriol concentration during the third trimester of normal pregnancy is described. The performance characteristics of the method were established by determining the non-specific binding, the blank value of the endogenous estriol free ("stripped") saliva, the recovery experiment and intra- and interassay coefficient of the variations. The corresponding serum samples were also analyzed by the same method. An excellent correlation was found between salivary and serum estriol concentrations.     

A comparison of serum androgens in pre-eclamptic and normotensive pregnant women during the third trimester of pregnancy

Objective: To compare the serum androgens level during the third trimester of pregnancy between normotensive and pre-eclamptic women. Method: A case-control study was performed on 64 pregnant women with the gestational age of 28-34 weeks. 32 women were pre-eclamptic (case group), and 32 women were normotensive till term gestation (control group). The serum level of androgens including sex hormone binding globulin (SHBG), total and free testosterone, androstenedione (ADD), and dehydroepiandrosterone sulfate (DHEA-S), were compared between the two groups. Results: The women of the two groups had no statistically significant difference according to age, gestational age, BMI (body mass index), parity and fetal sex. Serum level of SHBG (90.86 ± 9.30 vs. 55.86 ± 8.02 nmol/l, p = 0.02), total testosterone (3.70 ± 0.57 vs. 2.06 ± 0.24 ng/ml, p = 0.01), free testosterone (1.28 ± 0. 17 vs. 0. 74 ± 0.07 pg/ml, p = 0.01), and ADD (2.47 ± 0.10 vs. 2.17 ± 0.10 ng/ml, p = 0.04), was higher in the pre-eclamptic women. However, there was no difference between the two groups for DHEA-S (0.75 ± 0.18 vs. 0.51 ± 0.08 μg/ml, p = 0.19). Conclusion: Serum androgen levels during third trimester of pregnancy are higher in pre-eclamptic women and this may propose an effect of androgens in the pathogenesis of pre-eclampsia.     

Forces required for dilatation of human cervix in first trimester of pregnancy

Cervical resistance to dilatation was measured in 76 patients undergoing first trimester legal abortion; a specially designed force-sensing instrument was used. No correlation between cervical resistance and patient age or gestational age was found. Increasing parity and earlier legal abortions were significantly correlated with a lowering of the cervical resistance. In patients dilated to 11 mm a lowering of resistance was noted suggesting a tear in cervical tissue.     

Subcutaneous continuous insulin infusion and control of blood glucose concentration in diabetics in third trimester of pregnancy.

The effect of subcutaneous continuous insulin infusion on the control of blood glucose concentrations was assessed in eight pregnant diabetics in the third trimester. Twenty-four-hour glucose profiles were obtained after strict inpatient control on conventional insulin regimens and after the start of the continuous infusion, which was maintained for 5-55 days. Mean 24-hour glucose concentrations (6.2 mmol/l on conventional regimen, 5.9 mmol/l on continuous infusion; 111.6 and 106.2 mg/100 ml respectively) and mean fasting concentrations (5.3 v 6.2 mmol/l; 95.4 v 111.6 mg/100 ml) were not significantly changed by continuous infusion. Diurnal variations in glucose concentration tended to be smaller on continuous infusion: standard deviation from mean 24-hour glucose concentration was reduced from 2.5 to 2.0 mmol/l (from 45 to 36 mg/100 ml), maximum excursion from 8.4 to 7.4 mmol/l (151.2 to 133.2 mg/100 ml), and M value from 16 to 14. Subcutaneous continuous insulin infusion may be useful in limiting diurnal variations of blood glucose concentrations and warrants further investigation since such an action may be beneficial in the management of pregnant diabetics, in whom the best possible control of blood glucose concentrations is sought for the good of the fetus.     

Ontological differences in first compared to third trimester human fetal placental chorionic stem cells

Human mesenchymal stromal/stem cells (MSC) isolated from fetal tissues hold promise for use in tissue engineering applications and cell-based therapies, but their collection is restricted ethically and technically. In contrast, the placenta is a potential source of readily-obtainable stem cells throughout pregnancy. In fetal tissues, early gestational stem cells are known to have advantageous characteristics over neonatal and adult stem cells. Accordingly, we investigated whether early fetal placental chorionic stem cells (e-CSC) were physiologically superior to their late gestation fetal chorionic counterparts (l-CSC). We showed that e-CSC shared a common phenotype with l-CSC, differentiating down the osteogenic, adipogenic and neurogenic pathways, and containing a subset of cells endogenously expressing NANOG, SOX2, c-MYC, and KLF4, as well as an array of genes expressed in pluripotent stem cells and primordial germ cells, including CD24, NANOG, SSEA4, SSEA3, TRA-1-60, TRA-1-81, STELLA, FRAGILIS, NANOS3, DAZL and SSEA1. However, we showed that e-CSC have characteristics of an earlier state of stemness compared to l-CSC, such as smaller size, faster kinetics, uniquely expressing OCT4A variant 1 and showing higher levels of expression of NANOG, SOX2, c-MYC and KLF4 than l-CSC. Furthermore e-CSC, but not l-CSC, formed embryoid bodies containing cells from the three germ layer lineages. Finally, we showed that e-CSC demonstrate higher tissue repair in vivo; when transplanted in the osteogenesis imperfecta mice, e-CSC, but not l-CSC increased bone quality and plasticity; and when applied to a skin wound, e-CSC, but not l-CSC, accelerated healing compared to controls. Our results provide insight into the ontogeny of the stemness phenotype during fetal development and suggest that the more primitive characteristics of early compared to late gestation fetal chorionic stem cells may be translationally advantageous.     

Profiles of steroids during third trimester of pregnancy in women: Effect of hot, dry desert environment

1. 1.|Profile of steroids were determined in either serum or urine of nonparous desert dwelling women, in summer (June–September) and in winter (December–February), both during the latter part of pregnancy or the luteal phase of the menstrual cycle.

2. 2.|Progesterone concentration was consistently lower in serum of women having their third trimester of pregnancy during summer. No such changes were noted in the concentration of unconjugated oestriol.

3. 3.|The urinary excretion rate of glucocorticoids, mineralocorticoids and their metabolites by women in week 35 of pregnancy during summer differed from that excreted by women during winter.

4. 4.|None of the changes in the profiles of steroids attributable to the natural thermal load of the summer season was associated with abrogation of pregnancy and foetal distress.

Differences in gene expression between first and third trimester human placenta: a microarray study

Background

The human placenta is a rapidly developing organ that undergoes structural and functional changes throughout the pregnancy. Our objectives were to investigate the differences in global gene expression profile, the expression of imprinted genes and the effect of smoking in first and third trimester normal human placentas.

Materials and Methods

Placental samples were collected from 21 women with uncomplicated pregnancies delivered at term and 16 healthy women undergoing termination of pregnancy at 9–12 weeks gestation. Placental gene expression profile was evaluated by Human Genome Survey Microarray v.2.0 (Applied Biosystems) and real-time polymerase chain reaction.

Results

Almost 25% of the genes spotted on the array (n = 7519) were differentially expressed between first and third trimester placentas. Genes regulating biological processes involved in cell proliferation, cell differentiation and angiogenesis were up-regulated in the first trimester; whereas cell surface receptor mediated signal transduction, G-protein mediated signalling, ion transport, neuronal activities and chemosensory perception were up-regulated in the third trimester. Pathway analysis showed that brain and placenta might share common developmental routes. Principal component analysis based on the expression of 17 imprinted genes showed a clear separation of first and third trimester placentas, indicating that epigenetic modifications occur throughout pregnancy. In smokers, a set of genes encoding oxidoreductases were differentially expressed in both trimesters.

Conclusions

Differences in global gene expression profile between first and third trimester human placenta reflect temporal changes in placental structure and function. Epigenetic rearrangements in the human placenta seem to occur across gestation, indicating the importance of environmental influence in the developing feto-placental unit.