Early Phase Of Gestation Research Articles

Interferon-Tau in Maternal Peripheral Blood and Its Relationship with Progesterone and Pregnancy-Associated Glycoproteins in the Early Phases of Gestation in Water Buffalo.

The aim of this study was to investigate the interferon tau (IFNt) concentration in the peripheral maternal blood during the early phase of pregnancy in buffalo cows and improve the knowledge on the physiological importance of circulating IFNt, evaluating the possible interaction with pregnancy-associated glycoproteins (PAGs) and progesterone (P4). Blood samples were taken from buffalo cows on day 0 (day of AI), 7, 14, 18, 28, and 40 post insemination for the IFNt, PAG, and P4 analysis and to determine the IFNt mRNA expression. The animals were categorized ex post into Pregnant, Non-pregnant and Embryo mortality groups. The interferon value was influenced by group (p = 0.003), being always higher in pregnant buffalo cows than in non-pregnant ones, while the embryo mortality group showed intermediate values between those for pregnant and non-pregnant animals. The mRNA expression of IFNt was not influenced by groups or any time points. The regression analysis that included IFNt as the independent variable showed that PAGs, from day 18 (p < 0.01), and P4, from day 28 (p < 0.05), were positively associated with IFNt values. The close associations among IFNt, PAGs and P4 demonstrate that all three molecules work together for fetal-placental well-being and pregnancy support. Unfortunately, the great individual variability in circulating IFNt makes this analysis unsuitable for early pregnancy diagnosis.

Environmental factors influencing eastern North Pacific gray whale calf production 1994–2016

AbstractThis paper describes the relationship between eastern North Pacific gray whale calf production and environmental conditions in the Pacific Arctic where they feed. The results show how interannual variation in sea ice cover in the Bering and Chukchi Seas along with broader indices of North Pacific climate, such as Pacific Decadal Oscillation (PDO) and North Pacific Index (NPI), are linked to variation in gray whale reproductive output. Estimates of gray whale calf production were derived from 23 consecutive years (1994–2016) of shore‐based visual surveys conducted off California during the northward migration. PDO and NPI in combination with ice cover in the Bering and Chukchi Seas during the early phase of gestation appear to be important in explaining the observed variability in calf production. Of the 2,285 time series linear models evaluated, the model of best‐fit included PDO(July), Ice(June), NPI(February), and explained 60% of the observed variability in calf production. After elimination of two data outliers in calf production estimates (2013 and 2014) a model including Ice(May), PDO(May), and NPI(July) explained 90% of the variability. We conclude that access to prey early in the gestation period is critical to reproductive success in this population and may be important for other capital breeding mammals.

Growth from Birth Through Six Months for Infants of Mothers in the “Women First” Preconception Maternal Nutrition Trial

To evaluate whether the fetal linear growth effects of maternal nutrition supplementation would be maintained through 6months postnatal age. The Women First trial was a multicountry, individually randomized clinical trial that compared the impact of maternal nutrition supplementation initiated preconception (Arm 1) vs at ∼11weeks of gestation (Arm 2), vs no supplement (Arm 3); the intervention was discontinued at delivery. Trial sites were in Democratic Republic of Congo, Guatemala, India, and Pakistan. Analysis includes 2421 infants born to 2408 randomized women. Primary outcome was the trajectory of length-for-age z scores (LAZ) by arm, based on assessments at birth and 1, 3, and 6months. We fitted longitudinal models on growth from birth to 6months using generalized estimating equations; maternal intervention effects were evaluated, adjusting for site and baseline maternal covariates. Linear growth for Arms 1 and 2 was statistically greater than for Arm 3 in 3 of the 4 countries, with average pairwise mean differences in LAZ of 0.25 (95% CI 0.15-0.35; P<.001) and 0.19 (95% CI 0.09-0.28; P<.001), respectively. Compared with Arm 3, average overall adjusted relative risks (95% CI) for stunting (LAZ <-2) were lower for Arms 1 and 2: 0.76 (0.66-0.87; P<.001) and 0.77 (0.67-0.88; P<.001), respectively. Improved linear growth in early infancy observed for the 2 intervention arms supports the critical importance of maternal nutrition before conception and in the early phase of gestation. ClinicalTrials.gov: NCT01883193.

Toxoplasma gondii ROP16I Deletion: The Exacerbated Impact on Adverse Pregnant Outcomes in Mice.

Imbalance of Th1 and Th2 response at the maternal–fetal interface is considered as a radical event in the pathogenesis of immunity-related pregnant diseases. It has been demonstrated that the ROP16I, a rhoptry protein of Toxoplasma gondii, and the viable parasite with ROP16I may induce M2 macrophage polarization in host innate immunity and may be involved in the adverse pregnant outcomes. However, the mechanisms by which T. gondii-derived effectors subvert the immune tolerance in the pathology of pregnancy remain unclear. Here, we constructed the RH strain with ROP16I deletion (RHΔrop16) to explore the pathogenesis of abnormal pregnancy. We found that C57BL/6 mice infected with RHΔrop16 exhibited the increased resorption of fetuses and more severe adverse pathology of placentae at the early phase of gestation, as compared to the mice infected with RH wild type (RH WT) parasite. Additionally, RHΔrop16 strain infection significantly promoted M1 macrophage phenotypes of CD80 and CD86, and decreased CD206 expression of M2 macrophages, with upregulation of the iNOS and downregulation of the Arg-1 expression in placental homogenates. Simultaneously, the pro-inflammatory cytokines of IL-12 and TNF-α were elevated whereas the anti-inflammatory cytokine of TGF-β1 was dampened. Moreover, the p38α mitogen-activated protein kinase (p38α MAPK) was notably phosphorylated in placental macrophages infected with both RHΔrop16 and RH WT strains compared with the control. Taken together, our findings indicated that ROP16I deletion of type I RH strain may cause exacerbated adverse pregnant outcomes, which is attributable to subversion of the maternal immune tolerance due to the increased pro-inflammatory cytokines in the pregnant animals. The results also suggest that ROP16I might be a protective factor and other T. gondii-derived molecules might be involved in the M1–Th1 biased pathological process in aberrant pregnancy at the early phase of gestation.

Wyburn-Mason Syndrome

AbstractWyburn–Mason syndrome is a very rare neurocutaneous disorder characterized by unilateral arteriovenous malformations of the midbrain associated with vascular abnormalities of eye and optic pathways, as well as multiple cutaneous nevi, reddish-bluish in color. The co-occurrence of such anomalies can be explained by an embryonic anomaly occurring in common ancestor cells, with the more severe cases related to development errors in the very early phases of gestation. Central nervous system and vision may be severely impaired: affected individuals may present with acute headache, hemiplegia, and homonymous hemianopsia in half of the cases. Seizures, cerebellar dysfunction, acute psychiatric signs, hallucinations, and temporal/spatial disorientation are reported more rarely. A progressive mental illness can become evident later in up to 30% of cases. Surgical removal is indicated only in superficially located arteriovenous malformations, while nonsurgical strategies (i.e., embolization and radiation therapy) are indicated for most of the lesions and represent the gold standard option in the treatment of this syndrome.

Testing the correlation between experimentally-induced hypothyroidism during pregnancy and autistic-like symptoms in the rat offspring

Thyroid hormones are important for the development of the central nervous system. Since the fetal thyroid gland is not functioning until mid-gestation, transport of maternal thyroid hormones across the placenta is essential during the early phases of gestation. Maternal thyroid deficiency has been associated with a higher incidence of neurodevelopmental disorders in the newborns. The relationship between maternal hypothyroidism and the onset of autism spectrum disorders (ASD) in the offspring, however, is still debated. To address this issue, we used a validated animal model of prenatal hypothyroidism based on the administration of the thyroid peroxidase inhibitor methimazole (MMI, 0.02g/100ml in tap water) to rat dams from gestational day 9 up to delivery. The offspring was tested in behavioral tasks during infancy (PNDs 5, 9, 13) and adolescence (PND 35-40) to capture some of the core and associated symptoms of ASD. MMI-exposed pups were able to vocalize as controls when separated from the nest, and showed intact social discrimination abilities in the homing behavior test. At adolescence, the offspring from both sexes did not show an anxious-phenotype in the elevated plus maze and showed intact object recognition. However, MMI-exposed male rats showed increased novelty-directed exploratory behaviors: they solicited their partner to play more and showed more interest for novel rather than familiar objects compared to control rats. Our results show that prenatal MMI-induced hypothyroidism does not cause in the rat offspring behaviors that resemble core and associated ASD symptoms, like deficits in communication and social interaction and anxiety.

WT1 expression in the human fetus during development.

Wilms’ Tumor 1 (WT1) is a transcription factor involved in the development of the urogenital system. The purpose of this study was to analyze the immunoreactivity for WT1 protein in different tissues and organs in human fetuses in early phases of gestation. To this end, samples from multiple organs were obtained from 4 human fetuses, ranging from 7 up to 12 weeks of gestation. Each sample was formalin-fixed, paraffin embedded and immunostained for WT1. Our data show that WT1 is involved in development of multiple human organs in a more vast series of cells types than previously reported. Immunostaining for WT1 was characterized by a predominant cytoplasmic reactivity in the vast majority of cell types. Mesenchimal progenitors in the fetal lung, ductal plate progenitors in fetal liver, cap mesenchimal cells in the developing kidney, fetal zone cells in adrenal glands, atrial and ventricular cardiomyocytes in the fetal heart, radial glial cells in the fetal cerebral cortex and skeletal muscle cell precursors showed the highest levels of WT1 immunoreactivity. Future studies will be needed to detect differences in the expression of WT1 in various organs at different gestational ages, in order to better evaluate the role of WT1 in cell proliferation and differentiation during intrauterine human development.

Effects of ambient levels of air pollution generated by traffic on birth and placental weights in mice

To examine whether there is an association between fetal and/or placental weight and exposure to ambient levels of air pollution in mice. Chronic experiments on mice that were exposed to polluted vs. clean air. Environmental exposure to atmospheric pollution. Female Swiss mice (n = 70) were maintained at different stages of gestation in an exposure chamber located at an intersection with heavy traffic in a major city in Brazil. Control mice were maintained in a similar chamber, located adjacent to the exposure chamber but equipped with filters for particles and reactive gases. Animals were divided into six groups as follows: no exposure, exposure to a polluted chamber throughout gestation, exposure to a polluted chamber during the 1st week of pregnancy, exposure to a polluted chamber during the 2nd and 3rd weeks, exposure to a polluted chamber during the 1st and 2nd week, and exposure to a polluted chamber during the 3rd week. At the end of the gestational period, the determination of fetal and placental weight was performed after cesarean section. Exposure to air pollution during the 1st week of pregnancy promoted a significant reduction in fetal weight. Mice exposed to polluted air, in any phase of gestation, presented with lower placental weight in comparison to mice maintained in clean chambers. Exposure to ambient levels of traffic pollution at early phases of gestation is a determinant for decreased final fetal weight. Placental weight is reduced with exposure to air pollution at any phase of gestation.

Relationship between L/T ratio and LHR in the prenatal assessment of pulmonary hypoplasia in congenital diaphragmatic hernia

The lung to thorax transverse area ratio (L/T ratio) and the lung area to head circumference ratio (LHR) have been widely used for the assessment of pulmonary hypoplasia in fetal congenital diaphragmatic hernia (CDH). The aim of this study was to evaluate the relationship between the L/T ratio and the LHR, and to clarify the characteristics of these two indicators as prognostic predictors by means of retrospective concurrent measurements from the same subjects with prenatally diagnosed fetal CDH. The medical records of 55 fetuses who had undergone a prenatal evaluation of isolated CDH from 1988 to 2006 were studied. The L/T ratio and the LHR were determined as the early values (earliest measurement performed earlier than 33 weeks of gestation) and as the late values (latest measurement performed later than 34 weeks of gestation) and analyzed, as well as the clinical data. Of the 55 infants, 13 died resulting in a 76.4% survival rate. A correlation expressed in the linear equation [(LHR) = 14.4 x (L/T ratio) - 0.11] was recognized between the early L/T ratio and the early LHR. All cases with an early L/T ratio of less than 0.08, or with an early LHR less than 1.2, died. Of the 13 cases, 5 with an early L/T ratio not lower than 0.08, but less than 0.13, died. Of the 17 cases, 4 with an early LHR not lower than 1.2, but less than 2.0, died. All cases with an early L/T ratio not lower than 0.13, or with an early LHR not lower than 2.0, survived. In 24 cases, the late values, which were measured at an interval of more than 4 weeks, were compared with the early values. Although the L/T ratio was consistent, the LHR increased in the late value compared to the early value. A good linear correlation was recognized between the L/T ratio and the LHR in the early phase of gestation, and the cutoff point of the prognostic prediction was determined in both indicators. In contrast to the L/T ratio, a definite cutoff point throughout the gestation may not be available in the LHR, because there is a natural increase of the LHR in the late phase of gestation.

Commissuroplasty for Macrostomia

Macrostomia is a rare facial malformation caused by failure of mesodermal migration merging to obliterate the embryonic grooves between the maxillary and mandibular processes during the early phase of gestation. This kind of malformation may require the use of several surgical techniques to repair the facial structure. Bibliographic studies concerning the repair of this malformation are focused on the description of mucosa, muscle, and skin flaps disconnected between them. This article presents a description of a unique myomucosal flap from vermillion for the correction of the existing malformation in the oral commissure.

Behavioral Aggression Is Associated with the 2D:4D Ratio in Men but Not in Women

Abstract. Numerous studies have investigated the relationship between testosterone (T) and aggression but yielded inconsistent findings in healthy subjects. One possible reason for this might be the measurement of actual T-levels, ignoring that its role in neurodevelopment seems to be of predominant importance. The aim of our study was to further elucidate the effects of T availability during early phases of gestation, operationalized by the measurement of the 2nd to 4th digit ratio (2D:4D), on behavioral aggression in healthy volunteers. A low 2D:4D (indicating a long ring finger relative to the index finger) relates to high levels of prenatal T. A total number of 171 healthy subjects (98 men, 73 women) ranging in age from 20 to 30 years were tested. Participants were subjected to a modified version of a competitive reaction-time task, a commonly used and well-established tool to elicit and measure aggression (Taylor paradigm). They also completed self-report scales on trait aggression. Ventral surface scans of both hands were used to determine the 2D:4D ratio. As expected, the 2D:4D was lower in men as compared to women for both hands. Moreover, in contrast to questionnaire data, men reveal higher levels of aggression in the computer task compared to women. Finally, a negative correlation between 2D:4D and aggression was found in males but not in females. Results are discussed with respect to the usefulness of the 2D:4D construct as well as to sex differences in organizational effects of T.

ROLE OF ATP‐SENSITIVE POTASSIUM CHANNELS IN NORMAL AND HYPERTENSION‐ASSOCIATED PREGNANCY IN RATS

1. Activation of vascular ATP-sensitive K(+) (K(ATP)) channels has been implicated in vasodilator responses to pregnancy. 2. The effect of glibenclamide, a K(ATP) channel inhibitor, on systolic blood pressure (SBP) and renal function was evaluated in pregnant and non-pregnant spontaneously hypertensive rats, as well as in normotensive and hypertensive Wistar rats that had been made hypertensive by simultaneous treatment with N(G)-nitro-l-arginine methyl ester (0.4 mg/mL) and indomethacin (2 mg/kg, i.p.) from Day 1 of gestation. Pregnant animals received 10 mg/kg glibenclamide for 12 days starting at Day 7. In addition, the mRNA levels of the vascular K(ATP) channel (Kir6.2) were estimated in aorta and kidney using real-time reverse transcription-polymerase chain reaction on Day 19 of pregnancy. 3. The decreased SBP observed in pregnant Wistar rats was paralleled by an increase in Kir6.2 mRNA levels. Glibenclamide blunted systemic vasodilation and reduced the mRNA expression of Kir6.2. There was no pregnancy induced vasodilation and no change in Kir6.2 mRNA expression in SHR. Glibenclamide had no effect on pregnant SHR. Hypertensive Wistar rats exhibited high SBP, followed by increased Kir6.2 mRNA levels. The effects of glibenclamide were not evaluated in this group because glibenclamide induced intense vaginal bleeding. 4. The results of the present study suggest that K(ATP) channels may be involved in pregnancy induced vasodilation during normotensive pregnancy, but not in pregnant SHR. Glibenclamide may have an abortive effect if administered during the early phases of gestation or in association with nitric oxide and prostaglandin inhibitors.

HLA-G positive trophoblastic cells in transcervical samples and their isolation and analysis by laser microdissection and QF-PCR.

To assess the frequency of cytotrophoblastic cells in endocervical samples collected by lavage at early stages of gestation using a specific anti-HLA-G McAb (G233). From a set of four selected samples, cells identified by immunostaining were collected by laser microdissection and then tested by quantitative fluorescent polymerase chain reaction (QF-PCR) for the presence of paternally derived DNA markers, in order to establish their fetal origin. Syncytial fragments and cytotrophoblastic cells from 23 transcervical samples were identified by immunostaining with McAb G233 reacting against HLA-G antigen and with antibodies against cytokeratin. Slides from the same samples were also tested by fluorescent in situ hybridization (FISH), while selected samples were analysed by QF-PCR. Slides from four samples retrieved from mothers with male fetuses were immunolabelled and then cytotrophoblastic cells, syncytial fragments and maternal epithelial cells were collected by laser microdissection and tested by QF-PCR. All endocervical samples retrieved from mothers with male fetuses were found to contain some cells with chromosome Y-specific signals when tested by FISH. Using McAb anti- HLA-G, cytotrophoblastic cellular elements were detected in about 50% of the samples. From four samples, cellular elements identified by immunostaining as cytotrophoblast or syncytial fragments were collected by laser microdissection and shown to be of fetal origin when tested by QF-PCR for the presence of fetal DNA markers. These results confirm that, during an early phase of gestation, fetal cells are released in the lower uterine cavity and that they can be isolated and analysed for prenatal diagnosis of single gene defects and aneuploidies.

Polyunsaturated Fatty Acid Accretion in First- and Second-Trimester Human Fetal Brain: Lack of Correlation with Levels in Paired Placental Samples

Accretion of polyunsaturated fatty acids was examined in human fetal brain and the corresponding placenta from 20 pregnancies covering the gestational ages 9 to 22 weeks to provide data for the first and second trimesters and to complement existing data for the third trimester and early postnatal periods and also to investigate any correlation between the levels of polyunsaturated fatty acids in the developing brain and placenta. Brain polyunsaturated fatty acid (PUFA) accretion was evident in the earliest samples. During this early phase of gestation, a gradual increase in brain PUFA levels was noted. Levels of PUFA in the placental samples were stable during this period. Comparison of PUFA levels from each brain revealed no correlation with PUFA levels in the corresponding placenta. PUFA accretion in human fetal brain in the second trimester, the period of rapid proliferation of neuronal and glial elements, coincides with the onset of ganglioside accumulation. Although this study provides no direct evidence, finding stable levels of PUFA in placenta is consistent with the current concept that, in the human, the placenta is the principal source of PUFA for export to the fetus throughout gestation.

First trimester human trophoblast expresses both interferon-γ and interferon-γ-receptor

Interferon-γ (IFN-γ) is a lymphokine, produced by activated T lymphocytes, which plays a key regulatory role in the host immunological responses. In addition, IFN-γ is expressed by human and porcine trophoblast. As IFN-γ exerts its biological functions through specific cell surface receptors and a great number of IFN-γ receptors (IFN-γR) have been purified from human placenta, we have examined the relative distribution of IFN-γ and IFN-γR in human placental tissues at different stages of pregnancy. By using immunohistochemical analysis and monoclonal antibodies, it was found that IFN-γ expression is intense in the first trimester but almost imperceptible at term, whereas the expression of IFN-γR is present at both stages of pregnancy. For both lymphokine and receptor, the most intense expression was observed in villous syncytiotrophoblast and in extravillous interstitial trophoblast. From these results it appears that the expression of IFN-γR in trophoblast is related to the presence of the lymphokine in the early phase of gestation but not later. On this basis, it can be argued that IFN-γ exerts its functional role via an autocrine and/or a paracrine loop mainly during the first trimester.