Later Stages Of Gestation Research Articles

Maternal Testosterone Excess Contributes to Reproductive System Dysfunction of Female Offspring Mice.

Hyperandrogenism is considered 1 of the most important characteristics of polycystic ovary syndrome, which affects more than 10% of females of reproductive age and is a common cause of infertility. In addition to the effects on patients themselves, maternal androgen excess has also been reported to impair the growth and development of offspring. In our current study, we found that maternal testosterone (T) treatment during different gestational stages increased the percentage of atretic follicle and decreased corpus luteum formation in female offspring. In addition, decreased serum estradiol and increased T levels were also observed in female offspring of T-treated mice during late gestational stage. Further studies revealed that Forkhead box protein L2 (FOXL2) and Cytochrome P450 family 19 subfamily a member 1 (CYP19A1) expression in granulosa cells of these female offspring mice were decreased. By using mouse primary granulosa cells and the KGN cell line, we demonstrated that decreasing FOXL2 and CYP19A1 levels in ovarian granulosa cells partially may contribute to disturbed sex hormone synthesis in female offspring of T-treated mice during the late gestational stage. Findings from our current study highlight a critical role of excess maternal T exposure, especially during the late gestational stage, which could further lead to aberrant ovary development and sex hormone synthesis in female offspring.

Machine learning classification models for fetal skeletal development performance prediction using maternal bone metabolic proteins in goats.

BackgroundIn developing countries, maternal undernutrition is the major intrauterine environmental factor contributing to fetal development and adverse pregnancy outcomes. Maternal nutrition restriction (MNR) in gestation has proven to impact overall growth, bone development, and proliferation and metabolism of mesenchymal stem cells in offspring. However, the efficient method for elucidation of fetal bone development performance through maternal bone metabolic biochemical markers remains elusive.MethodsWe adapted goats to elucidate fetal bone development state with maternal serum bone metabolic proteins under malnutrition conditions in mid- and late-gestation stages. We used the experimental data to create 72 datasets by mixing different input features such as one-hot encoding of experimental conditions, metabolic original data, experimental-centered features and experimental condition probabilities. Seven Machine Learning methods have been used to predict six fetal bone parameters (weight, length, and diameter of femur/humerus).ResultsThe results indicated that MNR influences fetal bone development (femur and humerus) and fetal bone metabolic protein levels (C-terminal telopeptides of collagen I, CTx, in middle-gestation and N-terminal telopeptides of collagen I, NTx, in late-gestation), and maternal bone metabolites (low bone alkaline phosphatase, BALP, in middle-gestation and high BALP in late-gestation). The results show the importance of experimental conditions (ECs) encoding by mixing the information with the serum metabolic data. The best classification models obtained for femur weight (Fw) and length (FI), and humerus weight (Hw) are Support Vector Machines classifiers with the leave-one-out cross-validation accuracy of 1. The rest of the accuracies are 0.98, 0.946 and 0.696 for the diameter of femur (Fd), diameter and length of humerus (Hd, Hl), respectively. With the feature importance analysis, the moving averages mixed ECs are generally more important for the majority of the models. The moving average of parathyroid hormone (PTH) within nutritional conditions (MA-PTH-experim) is important for Fd, Hd and Hl prediction models but its removal for enhancing the Fw, Fl and Hw model performance. Further, using one feature models, it is possible to obtain even more accurate models compared with the feature importance analysis models. In conclusion, the machine learning is an efficient method to confirm the important role of PTH and BALP mixed with nutritional conditions for fetal bone growth performance of goats. All the Python scripts including results and comments are available into an open repository at https://gitlab.com/muntisa/goat-bones-machine-learning.

Evidence-based in vivo tocolytic activities of Alchornea laxiflora (Benth) (Euphorbiaceae) in female rats

Background and objectives: The leaves of Alchornea laxiflora are used in herbal medicine as a remedy for threatened abortion. This study was designed to scientifically evaluate the tocolytic effect of the aqueous and methanolic extracts of Alchornea laxiflora leaves on implantation and last term of pregnancy in rats.Methods: For the implantation test, spermpositive females were orally given either distilled water (10 ml/kg), salbutamol (0.2 mg/kg), aqueous or methanolic extract (55 and 100 mg/kg) of Alchornea laxiflora from day 1 to day 7 of pregnancy. For the late pregnancy study, some gestational parameters (duration of pregnancy, number and weight of pups at birth) were measured after treating pregnant females, as in the implantation test, from day 17 to day 25.Results: For the implantation test, all sperm-positive females showed implantation sites and, the duration of gestation, the resorption rate, the litter size and the weight of pups at birth were unaffected at delivery compared to control. For the last term pregnancy, Alchornea laxiflora extracts also expressed a tocolytic activity ranking from 28.57% (aqueous extract, 100 mg/kg) to 71.4% (methanolic extract, 55 mg/kg). No significant differences were observed regarding the mean litter size and the variation in body weight between the treatment groups. Salbutamol produced similar effects.Conclusion: Treatment of females at late gestation stage with plant extracts and salbutamol extended the expected delivery period. These results support the tocolytic traditional claim regarding Alchornea laxiflora.Keywords: Alchornea laxiflora, implantation, parturition, tocolysis, rat

Learn from Your Elders: Developmental Biology Lessons to Guide Maturation of Stem Cell-Derived Cardiomyocytes.

Human pluripotent stem cells (hPSCs) offer a multifaceted platform to study cardiac developmental biology, understand disease mechanisms, and develop novel therapies. Remarkable progress over the last two decades has led to methods to obtain highly pure hPSC-derived cardiomyocytes (hPSC-CMs) with reasonable ease and scalability. Nevertheless, a major bottleneck for the translational application of hPSC-CMs is their immature phenotype, resembling that of early fetal cardiomyocytes. Overall, bona fide maturation of hPSC-CMs represents one of the most significant goals facing the field today. Developmental biology studies have been pivotal in understanding the mechanisms to differentiate hPSC-CMs. Similarly, evaluation of developmental cues such as electrical and mechanical activities or neurohormonal and metabolic stimulations revealed the importance of these pathways in cardiomyocyte physiological maturation. Those signals cooperate and dictate the size and the performance of the developing heart. Likewise, this orchestra of stimuli is important in promoting hPSC-CM maturation, as demonstrated by current in vitro maturation approaches. Different shades of adult-like phenotype are achieved by prolonging the time in culture, electromechanical stimulation, patterned substrates, microRNA manipulation, neurohormonal or metabolic stimulation, and generation of human-engineered heart tissue (hEHT). However, mirroring this extremely dynamic environment is challenging, and reproducibility and scalability of these approaches represent the major obstacles for an efficient production of mature hPSC-CMs. For this reason, understanding the pattern behind the mechanisms elicited during the late gestational and early postnatal stages not only will provide new insights into postnatal development but also potentially offer new scalable and efficient approaches to mature hPSC-CMs.

Is scanning for vasa previa important for singleton pregnancies that started as multiple conceptions?

ObjectivesVasa previa (VP) is a congenital placentation disorder in which fetal vessels run across the internal os of the cervix under the fetal presentation. This rare condition is associated with a high rate of perinatal morbidity and mortality when undetected before delivery. Roughly 85% of all cases of VP can be associated with one or more identifiable risk factors including in-vitro fertilization (IVF), multiple gestations, bilobed, succenturiate or low-lying placentas, and velamentous cord insertion (VCI). Recent evidence indicates the need for standardized prenatal targeted scanning protocols of pregnancies at risk of VP. The present study reports on pregnancies that began with multiple gestations but ended with a single fetus diagnosed with VP. Study designWe retrospectively collected and reviewed medical records from 2006 to 2018 of early multiple pregnancies that ended with a single fetus diagnosed with VP in our medical center, including three cases of twin gestation complicated by a vanishing twin and a case of multifetal reduction in triplet pregnancy. This retrospective cohort study was approved by our Institutional Clinical Research Committee. ResultsThe database search identified 50 pregnancies that started as multiple gestations but continued as singletons. Of these, 4 pregnancies were diagnosed with VP, for a prevalence of 8.0%. For two of the four cases, the diagnosis was made during delivery as expressed by a low Apgar score at 1 and 5 min, a low cord blood pH value, newborn resuscitation, blood product transfusion, and NICU supervision. There was a statistically significant difference in the prevalence of VP in pregnancies that started as multiple gestations but continued later as singletons compared to multiple pregnancies (8.0% vs. 0.2% respectively, p < 0.0001). The OR for VP in pregnancies that started as multiple gestations but continued as singletons was 41.1 (95% CI, 12.77–131.94). ConclusionsOur findings suggest there is an increased risk of VP in conceptions that started as viable multiple gestations but continued later as singletons. If our findings supported by others, it may be prudent to consider all twins at the beginning of pregnancy to be at risk for VP, irrespective of the actual number of life fetuses at later stages of gestation.

Pregnancy Promotes Maternal Hippocampal Neurogenesis in Guinea Pigs.

Adult neurogenesis in the hippocampal dentate gyrus (DG) modulates cognition and behavior in mammals, while motherhood is associated with cognitive and behavioral changes essential for the care of the young. In mice and rats, hippocampal neurogenesis is reported to be reduced or unchanged during pregnancy, with few data available from other species. In guinea pigs, pregnancy lasts ~9 weeks; we set to explore if hippocampal neurogenesis is altered in these animals, relative to gestational stages. Time-pregnant primigravidas (3-5 months old) and age-matched nonpregnant females were examined, with neurogenic potential evaluated via immunolabeling of Ki67, Sp8, doublecortin (DCX), and neuron-specific nuclear antigen (NeuN) combined with bromodeoxyuridine (BrdU) birth-dating. Relative to control, subgranular Ki67, Sp8, and DCX-immunoreactive (+) cells tended to increase from early gestation to postpartum and peaked at the late gestational stage. In BrdU pulse-chasing experiments in nonpregnant females surviving for different time points (2-120 days), BrdU+ cells in the DG colocalized with DCX partially from 2 to 42 days (most frequently at 14-30 days) and with NeuN increasingly from 14 to 120 days. In pregnant females that received BrdU at early, middle, and late gestational stages and survived for 42 days, the density of BrdU+ cells in the DG was mostly high in the late gestational group. The rates of BrdU/DCX and BrdU/NeuN colocalization were similar among these groups and comparable to those among the corresponding control group. Together, the findings suggest that pregnancy promotes maternal hippocampal neurogenesis in guinea pigs, at least among primigravidas.

Circulating NT-proBNP but not soluble corin levels were associated with preeclampsia in pregnancy-associated hypertension

BackgroundCorin is a serine protease known to convert B-type natriuretic peptide (BNP) prohormone into BNP and its amino-terminal fragment (NT-proBNP). In mice lacking corin, high blood pressure and proteinuria were found at late gestational stages, with associated delayed trophoblast invasion and impaired spiral artery remodeling in the uterus. We hypothesize that both NT-proBNP and soluble corin elevation predict the presence of preeclampsia in pregnant patients with hypertension. MethodsWe prospectively enrolled 149 pregnant women with a history of chronic hypertension or gestational hypertension presenting at a tertiary-care hospital. We compared plasma NT-proBNP and soluble corin concentrations based on their preeclamptic status. ResultsIn our study cohort, 62 patients with preeclampsia had lower gestational age than 87 patients without preeclampsia (33.3 ± 3 versus 36.6 ± 3 weeks; P < .001), otherwise the baseline characteristics were similar. We observed higher NT-proBNP concentrations in patients with preeclampsia compared to those without preeclampsia (304.3 [96.34, 570.4] vs. 60.8 [35.61, 136.8] ng/L, P < .001), with no differences between chronic and gestational hypertension. However, the concentration of corin was not statistically different between the two groups (1756 [1214, 2133] vs. 1571 [1171, 1961] ng/L, P = .1087). ROC curve analysis demonstrated stronger predictive value of NT-proBNP compared to soluble corin in predicting the presence of preeclampsia in our study population (AUC 0.7406 vs. 0.5789, P < .0001). ConclusionWhile corin may contribute to mechanistic underpinnings of the development of preeclampsia in animal models, soluble corin likely has no diagnostic role in human pregnancies for preeclampsia beyond natriuretic peptide levels.

Public Reason and Abortion: Was Rawls Right After All?

In ‘Public Reason and Prenatal Moral Status’ (2015), Jeremy Williams argues that the ideal of Rawlsian public reason commits its devotees to the radically permissive view that abortion ought to be available with little or no qualification throughout pregnancy. This is because the only (allegedly) political value that favours protection of the foetus for its own sake—the value of ‘respect for human life’—turns out not to be a political value at all, and so its invocation in support of considerations bearing upon the permissibility of abortion is beyond public reason’s remit. Thus, it will scarcely if ever be legitimate to restrict women’s equality and bodily autonomy for the sake of the foetus, even at full term. In this paper, I argue that Williams fails to establish that Rawlsian reasonable citizens must endorse the radically permissive stance vis-a-vis abortion. Citizens can, I claim, reasonably accord the value of respect for human life weight, and indeed converge on the claim that it outweighs other salient political values, during later stages of gestation. Nevertheless, Williams’s argument gets something right in that it reveals why the value of respect for human life is inadmissible at the bar of public reason in early stages of pregnancy. But then, far from throwing Rawlsian public reason into disrepute, Williams’s argument actually (albeit inadvertently) provides arguably more compelling grounds than any hitherto rallied for endorsing Rawls’s much maligned claim that opposition to the duly qualified right to abortion in the first trimester of pregnancy is ‘unreasonable’.

Critical time window of fenvalerate-induced fetal intrauterine growth restriction in mice

Fenvalerate (FEN), a representative type II pyrethroid, is a widely used pyrethroid insecticide and a potential environmental contaminant. Several studies demonstrated that gestational FEN exposure induced intrauterine growth restriction (IUGR). However, the critical time window of FEN-induced fetal IUGR remains obscure. The present study aimed to identify the critical window of FEN-induced fetal IUGR. Pregnant mice were administered corn oil or FEN (20 mg/kg) by gavage daily at the early gestational stage (GD0-GD6), middle gestational stage (GD7-GD12) or late gestational stage (GD13-GD17). The results showed that the rates of fetal IUGR were markedly increased only in the mice exposed to FEN on GD13-GD17 but not in the mice exposed to FEN on GD7-GD12 or GD0-GD6. Further analysis showed that the blood sinusoid area in the placental labyrinth layer was reduced in the mice exposed to FEN on GD13-GD17. In addition, CD34+ microvessel density in the labyrinthine region was decreased in the male and female fetuses whose mothers were exposed to FEN on GD13-GD17. Mechanistic analysis found that the glutathione level was decreased in the FEN-exposed placentas. In contrast, the levels of 3-nitrotyrosine and malondialdehyde, two oxidative stress markers, were increased in FEN-exposed placentas. Heme oxygenase-1, inducible nitric oxide synthase, catalase and peroxiredoxin-3, which are antioxidant enzymes, were upregulated in the FEN-exposed placentas. The present study suggests that the late gestational stage is a critical time window of FEN-induced fetal IUGR. Placental oxidative stress may be, at least partially, involved in the process of FEN-induced placental damage and fetal IUGR.

Gestational Geophagia Affects Nephrocardiac Integrity, ATP-Driven Proton Pumps, the Renin⁻Angiotensin⁻Aldosterone System, and F2-Isoprostane Status.

Pregnancy brings about strong cravings for nonfood materials, the gestational toxicities of which are not yet ascertained. In this study, we used rat models to investigate the effect of clay beverage consumption during early and late gestation on p-Type ATPases, nephrocardiac integrity, the antioxidant system, and on the activities of the renin–angiotensin–aldosterone system (RAAS). The rats at early (7th day) and late gestation (20th) were administered single doses (500 mg/kg body weight) of clay beverage and examined using ELISA and spectrophotometry. The gestational clay beverage intake significantly elevated the renal hemodynamics, glomerular filtration rate (GFR), anion gap, urinary output, and blood urea nitrogen–creatinine ratio (BUN/Crt). At early and late gestation, clay beverage consumption elevated the heartbeat, atherogenic index of plasma, cardiac risk ratio, and atherogenic coefficients. Creatinine kinase and troponin levels after clay beverage consumption significantly increased with gestation age, while lactate dehydrogenase elevation was independent of gestation age. Mg2+-ATPase and Na+/K+-ATPase significantly decreased during gestation and were further altered with clay beverage intake. The rats showed higher RAAS activities during early and late gestation stages but greatly decreased activities after clay beverage administration. When F2-isoprostane and malondialdehyde levels were measured, slight elevations were found during pregnancy and were greatly elevated with clay beverage intake, while the glutathione reductase, catalase, and superoxide dismutase levels were decreased. We thus discourage clay beverage consumption throughout the entire pregnancy period because of these profound homeostatic imbalances and organ toxicities associated with its consumption.

Outcomes of self-induced late pregnancy termination in women presenting to a tertiary hospital in the Eastern Cape Province, South Africa.

Little is known about the outcomes of self-induced pregnancy termination after 24 weeks' gestation, as previous studies have concentrated on outcomes before 24 weeks. To investigate the gestational age, misoprostol dosage, source of information on misoprostol, reasons for termination and outcomes of self-induced pregnancy termination after 24 weeks' gestation. A quantitative, retrospective case series observational research design was utilised. Paediatric case summaries and the Perinatal Problem Identification Programme were used to collect data. Cases of self-induced pregnancy termination using misoprostol after 24 weeks' gestation treated at a tertiary hospital in the Eastern Cape Province, South Africa, during the period 1 July 2011 - 1 January 2012 were identified and included in the study. Frequencies and proportions were used to analyse data. Eighteen known cases of self-induced pregnancy termination using misoprostol after 24 weeks' gestation were treated at the hospital during the 6-month study period. Misoprostol doses ranged from 400 to 1 200 µg. Birth weight was &lt;500 g in 1 case (6%), 500- 1499 g in 12 (67%), 1 500 - 1 999 g in 2 (11%), &gt;2 500 g in 1 (6%) and unknown in 1 (6%). Eleven of the babies (67%) were born alive and 5 (28%) were stillborn (1 further stillbirth (6%) was classified as an abortion, &lt;500 g). One baby (6%) survived, and in 1 case (6%) the pregnancy continued. Eight of the 10 neonatal deaths were early and 2 were late. The major cause of neonatal death was hyaline membrane disease (n=8, 44%). Other causes were hypoxia (n=2), septicaemia (n=2), necrotising enterocolitis (n=2), pulmonary haemorrhage (n=2) and intraventricular haemorrhage (n=2). More than one cause applied in some cases. The maternal complications were manual removal of the placenta (n=2, 11%), ruptured uterus (n=1, 6%), and anaemia with blood transfusion (n=1, 6%). Self-administration of misoprostol to induce pregnancy termination after 24 weeks' gestation contributes to preterm births and perinatal morbidity and mortality. The findings of this study show that there is a need to educate women on the perinatal and maternal risks associated with self-induced pregnancy termination at a late stage of gestation, availability of safe options for pregnancy termination, and contraceptive use and adherence. Healthcare workers need to be sensitive to the possibility that cases of apparent spontaneous preterm labour or birth may have been self-induced.

Protective effects of quercetin against brain injury in a rat model of lipopolysaccharide-induced fetal brain injury

Maternal exposure to lipopolysaccharide (LPS), a bacterial endotoxin produced during infection, leads to disruption in fetal brain development and causes newborn brain injury. Quercetin (QR) is a multipotent flavonoid that functions as an antioxidant and protects against inflammation and neurodegeneration. In this study, we explored the potential functions of QR in alleviating maternal LPS exposure induced fetal brain damage. Pregnant rats at late gestational stages were treated with saline, LPS, QR, LPS and QR. Brain injury biomarker TGF-1β was assessed in cerebrospinal fluid (CSF) and brain tissue of newborn rats. Pro-inflammatory cytokines, apoptosis markers and oxidative stress indicators were evaluated. We found that LPS treatment induced an increased production of TGF-1β which was suppressed by QR administration. LPS enhanced pro-apoptotic Bax and inhibited anti-apoptotic Bcl-2 expression. QR reduced that ratio of Bax and Bcl-2 that was high in LPS treated brain tissue. Additionally, QR suppressed oxidative stress induced by LPS. Finally, QR reduced the levels of pro-inflammatory cytokines that were produced as a result of LPS exposure. In summary, our study indicates that QR potently alleviates maternal LPS exposure induced fetal brain injury in rats, making it a potential therapeutic for suppressing infant brain damage as a result of maternal infection.

Effects of dietary supplementation with lysozyme during late gestation and lactation stage on the performance of sows and their offspring.

This study investigated the effects of supplementing sow diets with lysozyme during the late gestation to lactation stage on the performance of sows and their offspring. Sixty sows (Yorkshire × Landrace, 3 to 6 of parity) at day 85 of gestation were allocated to the following 3 dietary treatments: 1) sows fed a basal diet from late gestation to lactation (control, n = 20), 2) sows fed a basal diet with lysozyme 150 g/t (LZM 150, n = 20), and 3) sows fed a basal diet with lysozyme 300 g/t (LZM 300, n = 20). During the lactation period, sows fed diets containing lysozyme had increased average daily feed intake (ADFI) (P < 0.01) and decreased weaning-to-estrus interval (WEI, P < 0.05), but there were no significant effects on backfat during the trial among treatments. Sows fed lysozyme diets had increased (P < 0.05) serum concentration of total protein (TP) compared with those fed the control diets. Serum immunoglobulin M (IgM) of the sows increased (P < 0.05) on day 1 of lactation, immunoglobulin A (IgA) and interleukin-10 (IL-10) increased (P < 0.05) on day 7 of lactation, and immunoglobulin G (IgG) had a tendency to increase (P = 0.05) during the lactation. Milk concentration of IgA increased (P < 0.05) on day 1 and 7 of lactation and tended to be greater (P = 0.06) on day 21 of lactation. No significant differences among the dietary treatments were observed in placental tissue mRNA expression of interleukin-6 (IL-6), IL-10, tumor necrosis factor-α (TNF-α), polymeric immunoglobulin receptor (pIgR), or the concentrations of IL-6, IL-10, TNF-α, or secretory immunoglobulin A (sIgA). Moreover, there was a decrease (P < 0.05) in stillborn in sows fed lysozyme diets. The diarrhea rate decreased (P < 0.05) and serum concentrations of IgA, IgG, IgM, and IL-10 increased (P < 0.05) in piglets from sows fed the diets containing lysozyme compared with piglets from sows fed the control diet. The serum concentrations of TP increased (P < 0.05), and albumin (ALB) and globulin (GLB) had a tendency to increase (P = 0.08, P = 0.06) in piglets from sows fed the diets containing lysozyme compared with piglets from sows fed the control diet. In conclusion, this study indicates that feeding sows diets supplemented with lysozyme from the late gestation through lactation stage increased sow ADFI during the lactation, shortened the WEI, and improved the maternal and offspring health status as indicated by immunological characteristics and a reduced incidence of diarrhea in piglets.

Development and evaluation of in murine model, of an improved live-vaccine candidate against brucellosis from to Brucella melitensis vjbR deletion mutant

Brucellosis is an infectious disease that brings enormous economic burdens for developing countries. The Brucella melitensis (B. melitensis) M5-90 vaccine strain (M5-90) has been used on a large scale in China, but may cause abortions if given to pregnant goats or sheep subcutaneously during the late stages of gestation. Moreover, the vaccine M5-90 cannot differentiate natural from vaccinated infection. Therefore, a safer and more potent M5-90 vaccine is required. In this study, a vjbR mutant of M5-90 (M5-90ΔvjbR) was constructed and overcame these drawbacks. M5-90ΔvjbR strain showed reduced survival capability in murine macrophages (RAW 264.7) and BALB/c mice and induced high protective immunity in mice. In addition, M5-90ΔvjbR induced an anti-Brucella-specific immunoglobulin G (IgG) response and stimulated the expression of gamma interferon (INF-γ) and interleukin-4 (IL-4) in vaccinated mice. Furthermore, M5-90ΔvjbR induced IgG response and stimulated the secretion of IFN-γ and IL-4 in immunized sheep. Moreover, the VjbR antigen allowed serological differentiation between infected and vaccinated animals. These results suggest that M5-90ΔvjbR is an ideal live attenuated and efficacious live vaccine candidate against B. melitensis 16 M infection.

Expression pattern of delta-like 1 homolog in developing sympathetic neurons and chromaffin cells

Delta-like 1 homolog (DLK1) is a member of the epidermal growth factor (EGF)-like family and an atypical notch ligand that is widely expressed during early mammalian development with putative functions in the regulation of cell differentiation and proliferation. During later stages of development, DLK1 is downregulated and becomes increasingly restricted to specific cell types, including several types of endocrine cells. DLK1 has been linked to various tumors and associated with tumor stem cell features. Sympathoadrenal precursors are neural crest derived cells that give rise to either sympathetic neurons of the autonomic nervous system or the endocrine chromaffin cells located in the adrenal medulla or extraadrenal positions. As these cells are the putative cellular origin of neuroblastoma, one of the most common malignant tumors in early childhood, their molecular characterization is of high clinical importance. In this study we have examined the precise spatiotemporal expression of DLK1 in developing sympathoadrenal cells. We show that DLK1 mRNA is highly expressed in early sympathetic neuron progenitors and that its expression depends on the presence of Phox2B. DLK1 expression becomes quickly restricted to a small subpopulation of cells in sympathetic ganglia, while virtually all chromaffin cells in the adrenal medulla and the Organ of Zuckerkandl still express high levels of DLK1 at late gestational stages.

Developmental SMAD6 loss leads to blood vessel hemorrhage and disrupted endothelial cell junctions

The BMP pathway regulates developmental processes including angiogenesis, yet its signaling outputs are complex and context-dependent. Recently, we showed that SMAD6, an intracellular BMP inhibitor expressed in endothelial cells, decreases vessel sprouting and branching both in vitro and in zebrafish. Genetic deletion of SMAD6 in mice results in poorly characterized cardiovascular defects and lethality. Here, we analyzed the effects of SMAD6 loss on vascular function during murine development. SMAD6 was expressed in a subset of blood vessels throughout development, primarily in arteries, while expression outside of the vasculature was largely confined to developing cardiac valves with no obvious embryonic phenotype. Mice deficient in SMAD6 died during late gestation and early stages of postnatal development, and this lethality was associated with vessel hemorrhage. Mice that survived past birth had increased branching and sprouting of developing postnatal retinal vessels and disorganized tight and adherens junctions. In vitro, knockdown of SMAD6 led to abnormal endothelial cell adherens junctions and increased VE-cadherin endocytosis, indicative of activated endothelium. Thus, SMAD6 is essential for proper blood vessel function during murine development, where it appears to stabilize endothelial junctions to prevent hemorrhage and aberrant angiogenesis.

Trichlorfon inhibits proliferation and promotes apoptosis of porcine trophectoderm and uterine luminal epithelial cells

Trichlorfon is an organophosphate insecticide widely used in agriculture. Additionally, it is applied to pigs for control of endo- and ectoparasites. Previous studies have shown the effects of trichlorfon in pigs during late stages of gestation; however, little is known about its effects during early pregnancy, including implantation and placentation. We investigated whether trichlorfon affects proliferation and apoptosis of porcine trophectoderm (pTr) and uterine luminal epithelial (pLE) cells. Trichlorfon inhibited the proliferation of pTr and pLE cells, as evidenced by cell cycle arrest, and altered the expression of proliferation-related proteins. In addition, trichlorfon induced cell death and apoptotic features, such as loss of mitochondrial membrane potential and DNA fragmentation, in pTr and pLE cells. Moreover, trichlorfon treatment decreased concentrations of Ca2+ in the cytoplasm in both cell lines and increased concentrations of Ca2+ in mitochondria of pTr cells. Trichlorfon inhibited the activation of phosphoinositide 3-kinase/AKT and mitogen-activated protein kinase signaling pathways in pTr and pLE cells. Therefore, we suggest that trichlorfon-treated pTr and pLE cells exhibited abnormal cell physiology which might lead to early pregnancy failure.

Clinical Presentation of Preeclampsia and the Diagnostic Value of Proteins and Their Methylation Products as Biomarkers in Pregnant Women with Preeclampsia and Their Newborns.

Preeclampsia (PE) is a disorder which affects 1-10% of pregnant women worldwide. It is characterised by hypertension and proteinuria in the later stages of gestation and can lead to maternal and perinatal morbidity and mortality. Other than the delivery of the foetus and the removal of the placenta, to date there are no therapeutic approaches to treat or prevent PE. It is thus only possible to reduce PE-related mortality through early detection, careful monitoring, and treatment of the symptoms. For these reasons the search for noninvasive, blood-borne, or urinary biochemical markers that could be used for the screening, presymptomatic diagnosis, and prediction of the development of PE is of great urgency. So far, a number of biomarkers have been proposed for predicting PE, based on pathophysiological observations, but these have mostly proven to be unreliable and inconsistent between different studies. The clinical presentation of PE and data gathered for the biochemical markers placental growth factor (PlGF), soluble Feline McDonough Sarcoma- (fms-) like tyrosine kinase-1 (sFlt-1), asymmetric dimethylarginine (ADMA), and methyl-lysine is being reviewed with the aim of providing both a clinical and biochemical understanding of how these biomarkers might assist in the diagnosis of PE or indicate its severity.

Expression of immune regulatory genes in early, mid and late stages of pig (Sus scrofa domesticus) gestation

Semi-allogeneic foetus and placenta exploit various mechanisms to avoid immune-mediated maternal rejection. Several factors and cytokines are attributed for production of immune tolerance during gestation and very little information on expression of these immune-regulatory genes is available in pig. Chorioallantoic membrane (CAM) from early, mid and late gestational stages (n=4) were analysed for expression of immune regulatory genes, viz. Fas ligand (FasL), transporter for antigen processing-1 (TAP-1), transforming growth factor β1 (TGF-β1) and macrophage migration inhibitory factor (MIF) whereas Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was employed as housekeeping gene. FasL gene expression was significantly higher in mid (13.46 fold) and late (28.77 fold) gestation than the early (1 fold) stage.TAP-1 mRNA expression was enhanced by 4.95 fold and 2.69 fold during mid and late gestation respectively in comparison to the early (1 fold) stage. TGF-β1 gene expression was up regulated in mid (2.43 fold) and late (2.29 fold) gestation than the early (1 fold) stage. MIF mRNA expression was enhanced in mid (3.04 fold) and late (1.59 fold) gestation in relation to the early (1 fold) stage. Placenta of pig remains entirely epitheliochorial which may minimise immune recognition and is supposed to diminish potent immune-regulatory mechanisms. However, our present study revealed consistent expression for immune regulatory factors which suggests immune modulation does exist in pig and may impart a role in pregnancy success.

Biochemical composition of amniotic fluid during different stages of gestation in Gaddi sheep

The study was conducted on amniotic fluid collected from fifty gravid uteri of Gaddi sheep at different stages of gestation. The foetii were measured for their crown rump length and then divided into 4 stages i.e. stage I (31-60 days), stage II (61-90 days), stage III (91-120 days) and stage IV (121- till term). The mean concentration of glucose showed a declining trend from stage I to stage IV of gestation. The level of total protein remained consistent initially and decreased slightly in later stages of gestation. Creatinine and urea increased from stage I and II to stage III of gestation. Activity of Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) was significantly higher in stage I of gestation. Alkaline Phosphatase showed highest activity in stage III of gestation. Changes in the concentration of glucose, urea, proteins or enzymes in foetal fluid reflect alterations in the functioning of liver during pregnancy and can be used as an important tool to assess the healthy state of pregnancy.