Showing papers on "Fetus published in 1996"
TL;DR: The data demonstrate the continued maternal circulation of fetalCD34+ or CD34+CD38+ cells from a prior pregnancy, which may represent a human analogue of the microchimerism described in the mouse and may have significance in development of tolerance of the fetus.
Abstract: Rare nucleated fetal cells circulate within maternal blood. Noninvasive prenatal diagnosis by isolation and genetic analysis of these cells is currently being undertaken. We sought to determine if genetic evidence existed for persistent circulation of fetal cells from prior pregnancies. Venous blood samples were obtained from 32 pregnant women and 8 nonpregnant women who had given birth to males 6 months to 27 years earlier. Mononuclear cells were sorted by flow cytometry using antibodies to CD antigens 3, 4, 5, 19, 23, 34, and 38. DNA within sorted cells, amplified by PCR for Y chromosome sequences, was considered predictive of a male fetus or evidence of persistent male fetal cells. In the 32 pregnancies, male DNA was detected in 13 of 19 women carrying a male fetus. In 4 of 13 pregnancies with female fetuses, male DNA was also detected. All of the 4 women had prior pregnancies; 2 of the 4 had prior males and the other 2 had terminations of pregnancy. In 6 of the 8 nonpregnant women, male DNA was detected in CD34+CD38+ cells, even in a woman who had her last son 27 years prior to blood sampling. Our data demonstrate the continued maternal circulation of fetal CD34+ or CD34+CD38+ cells from a prior pregnancy. The prolonged persistence of fetal progenitor cells may represent a human analogue of the microchimerism described in the mouse and may have significance in development of tolerance of the fetus. Pregnancy may thus establish a long-term, low-grade chimeric state in the human female.
1,212 citations
TL;DR: Preliminary data suggest that a type 2 cytokine profile may be associated with normal human pregnancy, whereas the lack of a dominant type 1 cytokineprofile may be indicative of a pathologic pregnancy.
Abstract: Antigen- and mitogen-stimulated cytokine production by peripheral blood mononuclear cells (PBMC) of 50 pregnant women and 31 age- and sex-matched non-pregnant controls were analysed to determine whether changes in cytokine production occur during normal and pathologic human gestation. The pregnant women, consecutively enrolled during a 3-month period, were undergoing a normal, non-pathologic pregnancy at the time of entry into the study, and underwent ultrasound examination to ascertain the exact week of pregnancy and the vitality of the fetus. Forty of the 50 pregnancies (80%) terminated physiologically with the birth of normal babies. Spontaneous abortions were observed in 5/50 (10%) women, and five women gave birth to newborns small for gestational age (SGA). A decrease in the production of IL-2 and interferon-gamma (IFN-γ) accompanied by an increase in production of IL-4 and IL-10, was observed in normal pregnancy, with the lowest quantities of IL-2 and IFN-γ and the highest quantities of IL-4 and IL-10 present in the third trimester of pregnancy. Statistically significant increased production of both IL-2 and IFN-γ and reduced production of IL-10 characterized pathologic pregnancies and distinguished them from normal pregnancies. These preliminary data suggest that a type 2 cytokine profile may be associated with normal human pregnancy, whereas the lack of a dominant type 2 cytokine profile may be indicative of a pathologic pregnancy.
607 citations
TL;DR: The physiological effect of tobacco on fetal growth seems to be a culmination of both the vasoconstrictive effects of nicotine on the uterine and potentially the umbilical artery and the effects on oxygenation by carboxyhemoglobin.
551 citations
TL;DR: The nutritional manipulation during pregnancy significantly increased systolic blood pressure in the resulting offspring in early adulthood, suggesting a possible common pathway whereby maternal environmental factors may influence fetal and placental growth and programme disease is inferred.
439 citations
TL;DR: The bilateral trafficking of nucleated cells between the fetus and the mother was studied using polymerase chain reaction (PCR)-based systems sensitive enough to detect 1 target cell in 100,000 background cells.
390 citations
TL;DR: The hypothesis that excess exposure of the fetoplacental unit to maternal glucocorticoids reduces birth weight and programs subsequent hypertension is supported and a key role for placental 11beta-HSD in controlling such exposure is indicated.
Abstract: Recent epidemiological studies have linked low birth weight with the later occurrence of cardiovascular and metabolic disorders, particularly hypertension. We have proposed that fetal exposure to excess maternal glucocorticoids may underpin this association. Normally, the fetus is protected from maternal glucocorticoids by placental 11beta-hydroxysteroid dehydrogenase (11beta-HSD). We have previously shown that treatment of pregnant rats with dexamethasone, a synthetic glucocorticoid that is poorly metabolized by the enzyme, reduces birth weight and produces elevated blood pressure in the adult offspring. Moreover, low activity of placental 11beta-HSD correlates with low birth weight in rats. Here, we show that maternal administration of carbenoxolone, a potent inhibitor of 11 beta-HSD, throughout pregnancy leads to reduced birth weight (mean 20 percent decrease) and elevated blood pressures (increase in mean arterial pressure, 9 mm Hg in males, 7 mm Hg in females) in the adult offspring of carbenoxolone-treated rats. This effect requires the presence of maternal adrenal products, as carbenoxolone given to adrenalectomized pregnant rats had no effect on birth weight or blood pressure. These data support the hypothesis that excess exposure of the fetoplacental unit to maternal glucocorticoids reduces birth weight and programs subsequent hypertension and indicate a key role for placental 11beta-HSD in controlling such exposure.
345 citations
TL;DR: Thickening of the basal lamina and congestion of the capillaries by erythrocytes are predicted to limit oxygen transfer from the interVillous space to the fetus and may represent an equilibration of oxygen tension between intervillous space and the terminal villi.
331 citations
TL;DR: The risk of NTDs increased with increasing prepregnant weight, independent of the effects of folate intake, in women in the greater metropolitan areas of Boston, Mass and Philadelphia, Pa.
Abstract: Objective. —To examine the relation between prepregnant weight and the risk of neural tube defects (NTDs). Design. —Data were collected from 1988 to 1994 in a case-control surveillance program of birth defects. Setting. —Study subjects were ascertained at tertiary care centers and birth hospitals in the greater metropolitan areas of Boston, Mass, and Philadelphia, Pa, and in southeastern Ontario. Participants. —Cases were 604 fetuses or infants with an NTD identified within 6 months of delivery. Controls were 1658 fetuses or infants with other major malformations identified within 6 months of delivery. For 1992 to 1994, there were 93 control infants without major malformations. Main Outcome Measure. —Relative risk of NTDs in infants or fetuses for different maternal weights. Results. —Relative to women who weighed 50 to 59 kg, risk of NTDs increased from 1.9 (95% confidence interval [CI], 1.2 to 2.9) for women weighing 80 to 89 kg to 4.0 (95% CI, 1.6 to 9.9) for women weighing 110 kg or more. When women were classified according to daily intake above or below the recommended level of 400 μg of folate, approximate threefold increases in risk were estimated for the heaviest weights in both groups. Intakes of 400 μg of folate or more reduced risk of NTDs by 40% among women weighing less than 70 kg, but no risk reduction was observed among heavier women. Conclusion. —The risk of NTDs increased with increasing prepregnant weight, independent of the effects of folate intake. (JAMA. 1996;275:1089-1092)
330 citations
TL;DR: Most known risk factors for spontaneousPreterm birth were not significantly associated with spontaneous preterm birth of twins and cervical length was the best predictor of spontaneous pre term birth at < 32 weeks, < 35 weeks, and < 37 weeks.
321 citations
TL;DR: The present findings are consistent with the premise that maternal-placental-fetal neuroendocrine parameters are significantly associated, both in magnitude and specificity, with features of maternal psychosocial functioning in pregnancy despite the systemic alterations associated with the endocrinology of pregnancy.
Abstract: Objective Physiological processes including neuroendocrine function have been proposed as mediators of the relationship between prenatal psychological state and pregnancy outcome; however, there are virtually no human studies that have systematically assessed such mechanisms. Neuroendocrine processes are significantly altered during pregnancy, and are characterized by the evolution of a transient neuroendocrine system, the placenta, and modifications in endocrine control mechanisms. Because these alterations have implications for neuroendocrine responsivity to exogenous conditions, the aim of the present study was to examine the cross-sectional association between prenatal psychosocial factors and stress-related neuroendocrine parameters during human pregnancy. Method Fifty-four adult women with a singleton, intrauterine pregnancy were recruited before 28 weeks of gestation. Maternal antecubital venous blood samples were withdrawn at 28 weeks of gestation for bioassays of adrenocorticotropin hormone (ACTH), beta-endorphin (beta E), and cortisol. Measures of prenatal stress, social support, and personality were collected using a two-part, self-report questionnaire administered at 28 and 30 weeks of gestation. Biomedical data were obtained from the medical record. Factors known to influence neuropeptide and hormone levels during pregnancy were controlled, including gestational age, circadian variation, and obstetric risk. Results In the present sample, prenatal psychosocial stress, social support, and personality variables were associated with neuroendocrine parameters in two primary ways. First, certain psychosocial factors were significantly associated with plasma levels of ACTH, beta E, and cortisol, and second, psychosocial factors were associated with a measure of disregulation of the normal relationship between two pro-opiomelanocortin (POMC) derivatives, ACTH and beta E. Furthermore, a combination of the maternal psychosocial and sociodemographic factors during pregnancy accounted for 36% of the variance in ACTH, 22% of the variance in the ACTH-beta E disregulation index, 13% of the variance in cortisol, and 3% of the variance in beta E. Conclusions The present findings are consistent with the premise that maternal-placental-fetal neuroendocrine parameters are significantly associated, both in magnitude and specificity, with features of maternal psychosocial functioning in pregnancy despite the systemic alterations associated with the endocrinology of pregnancy. These findings provide a basis for further investigations of the role of the neuroendocrine system as a putative mediating pathway between prenatal psychosocial factors and birth outcome, and possibly also as a mechanism linking features of the maternal psychosocial environment to fetal/infant brain development.
318 citations
TL;DR: The data support the notion that defiency of placental 11 β -HSD, by exposing the fetus to excess maternal glucocorticoids, reduces growth and predisposes to hyperglycaemia in later life.
Abstract: Recent human epidemiological studies have linked low birth weight with a substantially increased risk of non-insulin-dependent diabetes mellitus in later life. These data suggest that the intrauterine environment plays a crucial role in determining later glucose homeostasis, but the mechanism is unknown. We have proposed that exposure of the fetus to excess maternal glucocorticoids may underpin the epidemiological findings. Normally placental 11 β -hydroxysteroid dehydrogenase type 2 (11 β -HSD-2) protects the fetus from the normally higher maternal levels of glucocorticoids by inactivating corticosterone and cortisol to inert 11-keto products. Here we show that administration of carbenoxolone, an inhibitor of placental 11 β -HSD 2, to pregnant rats, leads to a significant reduction in average birth weight (20 % fall). At 6 months of age, the male offspring of carbenoxolone-treated pregnancies had similar weights to controls, but showed significantly higher fasting plasma glucose (6.0 ± 0.3 vs 4.8 ± 0.2 mmol/l; p < 0.01) and exhibited significantly greater plasma glucose (10 % higher) and insulin (38 % higher) responses to an oral glucose load. These effects of carbenoxolone require intact maternal adrenal glands suggesting that inhibition of feto-placental 11 β -HSD 2 is key. These data support the notion that defiency of placental 11 β -HSD, by exposing the fetus to excess maternal glucocorticoids, reduces growth and predisposes to hyperglycaemia in later life. [Diabetologia (1996) 39: 1299–1305]
TL;DR: That aerobic processes continue without hemoglobin O2 transport indicates the adequacy in the embryo of simple O2 diffusion alone even in developmental stages with extensive convective blood circulation generated by the heart.
Abstract: Embryonic hemoglobin circulated by the developing heart in the early vertebrate embryo is widely assumed (without substantiation) to perform the same vital role of O2 carriage that it does in fetuses and adults. In order to challenge this assumption, we measured highly O2-dependent physiological variables like O2 consumption, cardiac performance, and initial swim bladder filling in the presence and absence of functional hemoglobin in the embryos and early larvae of the zebra fish, Danio ( = Brachydanio) rerio. Functional ablation of hemoglobin by carbon monoxide or phenylhydrazine did not reduce whole-animal O2 consumption, which was approximately 85 to 90 mumol.g-1.h-1. Similarly, no differences in heart variables like ventricular pressure development or heart rate, which increased from 135 to 175 bpm between stages 36h and 96h (indicating developmental stages 36 and 96 hours after fertilization, respectively), were observed in these experiments. Initial opening of the swim bladder was not influenced in the presence of CO-occupied hemoglobin but was significantly impaired when the embryonic hemoglobin was chemically modified by incubation with phenylhydrazine. That aerobic processes continue without hemoglobin O2 transport indicates the adequacy in the embryo of simple O2 diffusion alone even in developmental stages with extensive convective blood circulation generated by the heart.
TL;DR: Although fetal fibronectin is an excellent test for predicting spontaneous preterm birth, it is presented no evidence that the use of this test will result in a reduction in spontaneous pre term birth.
TL;DR: It is suggested that in utero fetal exposure to an allergen from around 22 weeks gestation may result in primary sensitisation to that allergenic, leading to positive proliferative responses, at birth.
Abstract: Blood samples were obtained from fetuses and premature babies (n = 51) (15-34 weeks gestation) to determine at what stage the fetal immune system was able to produce a positive proliferative response to common allergens. Peripheral blood mononuclear cells (PBMC) were stimulated with the mitogen, phytohaemagglutinin (PHA), and the allergens, house dust mite, cat fur, birch tree pollen, beta-lactoglobulin, ovalbumin and bee venom (mellitin). Results were expressed as ratios of stimulated to unstimulated 3H thymidine incorporation, and as percent positive responders. There was an increase in proliferation ratio which correlated with increasing gestational age for PHA (p 22 weeks gestation compared to 22 weeks compared to < 22 weeks for the mitogen and all allergens, except mellitin. Maternal exposure to birch pollen, which has a discrete season, was assessed to determine whether exposure had occurred at 22 weeks gestation or beyond. Results showed a higher proliferative response in infant cells stimulated with birch pollen (p = 0.005) and higher proportion of positive responders (p = 0.01) in the group of babies whose mothers had been exposed to birch pollen beyond 22 weeks, compared to those whose mothers had not been so exposed. These results suggest that in utero fetal exposure to an allergen from around 22 weeks gestation may result in primary sensitisation to that allergen, leading to positive proliferative responses, at birth.
TL;DR: In two pregnancies at risk for sickle cell anaemia and β–thalassaemia, the fetal genotypes are successfully identified and prenatal diagnosis of single gene disorders by recovering fetal cells from maternal circulation appears to be a feasible approach.
Abstract: Currently, amniocentesis, chorionic villus sampling (CVS) and fetal blood sampling are used to obtain fetal cells for genetic diagnosis. These invasive procedures pose a small but not negligible risk for the fetus. Efforts have been directed towards the enrichment of fetal cells, such as erythroblasts, from maternal blood and progress has been made in the diagnosis of some chromosomal disorders and in sex determinations. We now report the detection of point mutations in single gene disorders using this method of prenatal diagnosis by enriching fetal cells from maternal blood by magnetic cell sorting followed by isolation of pure fetal cells by microdissection. In two pregnancies at risk for sickle cell anaemia and beta-thalassaemia, we successfully identified the fetal genotypes. Thus, prenatal diagnosis of single gene disorders by recovering fetal cells from maternal circulation appears to be a feasible approach.
TL;DR: A reciprocal relationship of radiosensitivity to anomalies and to embryonic or Fetal lethality supports the notion that embryonic or fetal tissues have a p53–dependent “guardian” of the tissue that aborts cells bearing radiation–induced teratogenic DNA damage.
Abstract: About half of human conceptions are estimated not to be implanted in the uterus, resulting in unrecognizable spontaneous abortions, and about 5% of human births have a recognizable malformation. In order to find clues to the mechanisms of malformation and abortion, we compared the incidences of radiation-induced malformations and abortions in p53 null (p53-/-) and wild-type (p53+/+) mice. After X-irradiation with 2 Gy on day 9.5 of gestation, p53-/- mice showed a 70% incidence of anomalies and a 7% incidence of deaths, whereas p53+/+ mice had a 20% incidence of anomalies and a 60% incidence of deaths. Similar results were obtained after irradiation on day 3.5 of gestation. This reciprocal relationship of radiosensitivity to anomalies and to embryonic or fetal lethality supports the notion that embryonic or fetal tissues have a p53-dependent "guardian" of the tissue that aborts cells bearing radiation-induced teratogenic DNA damage. In fact, after X-irradiation, the number of cells with apoptotic DNA fragments was greatly increased in tissues of the p53+/+ fetuses but not in those of the p53-/- fetuses.
TL;DR: The diagnosis of CPM is most commonly made when, after the diagnosis of chromosomal mosaicism in a CVS sample, the second prenatal testing (amniotic fluid culture or fetal blood culture analysis) shows a normal diploid karyotype.
Abstract: In most pregnancies the chromosomal complement detected in the fetus is also present in the placenta. The detection of an identical chromosomal complement in both the fetus and its placenta has always been expected as both develop from the same zygote. However, in approximately 2% of viable pregnancies studied by chorionic villus sampling (CVS) at 9 to 11 weeks of gestation, the cytogenetic abnormality, most often trisomy, is confined to the placenta. This phenomenon is known as confined placental mosaicism (CPM). It was first described by Kalousek and Dill in term placentas of infants born with unexplained intrauterine growth restriction (IUGR). Contrary to generalised mosaicism, which is characterised by the presence of two or more karyotypically different cell lines within both the fetus and its placenta, CPM represents tissue specific chromosomal mosaicism affecting the placenta only. The diagnosis of CPM is most commonly made when, after the diagnosis of chromosomal mosaicism in a CVS sample, the second prenatal testing (amniotic fluid culture or fetal blood culture analysis) shows a normal diploid karyotype.
TL;DR: Investigating the pathophysiology of CDH and its repair in fetal lambs found that obstructing the normal egress of fetal lung fluid enlarges developing fetal lungs, reduces the herniated viscera, and accelerates lung growth, resulting in improved pulmonary function after birth.
TL;DR: In-utero transplantation of haematopoietic progenitor cells allowed immune reconstitution of a fetus with SCIDXI and may be an alternative to elective abortion and should encourage applications of this method to other inherited disorders curable by BMT.
Journal Article•
TL;DR: This study is the first to demonstrate the presence of all components of the RAS in very early human development (30-35 days of gestation) and likely plays a role in the growth and differentiation of the kidney, adrenal gland, heart, and liver, all organs that are of major importance for the regulation of blood pressure later in life.
Abstract: Increasing evidence suggests that the renin-angiotensin system (RAS) is not only a potent regulator of blood pressure and fluid and electrolyte homeostasis, but that it also plays an important role in growth and differentiation in development as well as in pathological states. We, therefore, investigated the expression of all components of the RAS in the human embryo and fetus by in situ hybridization or immunohistochemistry. This study is the first to demonstrate the presence of all components of the RAS in very early human development (30-35 days of gestation). Angiotensinogen mRNA is expressed in very high amounts in the yolk sac, liver, and kidney, whereas renin mRNA and angiotensin-converting enzyme are expressed in the chorion, kidney, and heart, thus allowing fetal production of angiotensin II. This effector molecule of the RAS mediates its effects through binding to specific receptor types, AT1 and AT2. Both of these receptors are also expressed very early in development (24 days of gestation), suggesting a role for angiotensin II in organogenesis. Based on the expression pattern of these receptors, angiotensin II likely plays a role in the growth and differentiation of the kidney, adrenal gland, heart, and liver, all organs that are of major importance for the regulation of blood pressure later in life.
TL;DR: The ontogeny and corticosteroid induction of AQP1 in rat lung coincide with major physiological alterations in lung development; however, the distribution of AQp1 predicts the existence of other water channels in the alveolar epithelium.
Abstract: At birth water is rapidly reabsorbed from the distal lung in preparation for alveolar gas exchange. To investigate a potential role for the AQP1 water channel in development, lung membranes from fetal and perinatal rats were analyzed by immunoblot. First expression of AQP1 was noted in fetal rat lung at E19 (19th day of the 21-day gestation). The level of AQP1 increased fivefold from the last gestational day to the first postnatal day and persisted at high levels into adulthood. Maternal corticosteroids increased expression of AQP1 in fetal lung, an effect also seen in adult rats. AQP1 mRNA increased in rat pups treated with corticosteroids, suggesting at least partial regulation at the level of transcription. Immunohistochemical analyses with anti-AQP1 demonstrated the protein in peribronchial vessels and visceral pleura at E21 with increased postnatal expression. AQP1 was not expressed in airway epithelium, and only occasional alveolar pneumocytes were labeled. Immunoelectron microscopy revealed AQP1 on both apical and basolateral membranes of endothelial cells. The ontogeny and corticosteroid induction of AQP1 in rat lung coincide with major physiological alterations in lung development; however, the distribution of AQP1 predicts the existence of other water channels in the alveolar epithelium.
TL;DR: Evidence is suggested that low levels of placental 11 beta-HSD2 result in increased exposure of the fetus to maternal glucocorticoid and low birth weight, which may be an important mechanism linking changes in the in utero environment and common adult diseases.
TL;DR: To measure the mRNA levels of vascular endothelial growth factor and its receptor in the placenta following delivery after uncomplicated pregnancy and after pregnancies complicated by pre‐eclampsia.
TL;DR: It is suggested that 26 to 34 weeks could be the "critical period' during which the insult that leads to in-utero programming for the development of adult hypertension occurs and the findings of slow fetal renal growth rate and associated high renin concentrations seen in small-for-gestational-age fetuses could be implicated in an irreversible reno-vascular pathology leading to adult hypertension.
Abstract: 1. This study was designed to examine the changes in kidney morphometry during gestation in fetuses that were either appropriate or small for gestational age and the relationship between umbilical vein plasma active renin and kidney morphometry. 2. Serial ultrasound measurements of various morphometric and renal indices were performed in a cohort of 87 singleton fetuses from 22 to 38 weeks gestation. Blood was collected from the umbilical vein at delivery and active renin was measured from the plasma based on angiotensinogen I generated during incubation with plasma and ox renin substrate. 3. Growth in the longitudinal plane of fetal kidneys was similar in the small- and appropriate-for-gestational age groups; however, growth in the anterio-posterior, transverse and circumference planes of the kidneys was significantly slower in the small-for-gestational-age group after 26 weeks gestation. Differences in growth rate in the two groups were most marked between 26 and 34 weeks and persisted until delivery when the anterior-posterior diameter was significantly larger (P < 0.00001) in the appropriate-for-gestational-age group (26.1 +/- 2.5 mm compared with 19.8 +/- 2.6 mm). The mean umbilical vein active plasma renin concentration at delivery was significantly higher (P < 0.05) in the small-for-gestation-age group (274.4 +/- 32.9 mu-units/ml plasma) than in the appropriate-for-gestational-age group (164.9 +/- 28.3 mu-units/ml plasma). In addition, there were statistically significant inverse correlations between renin concentration and birthweight (r = -0.55, P < 0.001) and between renin concentration and kidney anterior-posterior diameter (r = -0.67, P < 0.001). 4. Fetal renal growth was slower in small than in appropriate-for-gestational-age fetuses. The period of 26-34 weeks gestation was that during which maximum fetal renal growth occurred. Umbilical vein plasma renin levels were higher in small-for-gestational-age fetuses. The findings of slow fetal renal growth rate and associated high renin concentrations seen in small-for-gestational-age fetuses could be implicated in an irreversible reno-vascular pathology leading to adult hypertension. We suggest that 26 to 34 weeks could be the "critical period' during which the insult that leads to in-utero programming for the development of adult hypertension occurs.
TL;DR: In FGR pregnancies, as an accommodation of the fetus to a restricted placental size and placental glucose transport capacity, the maternal-fetal glucose concentration difference is increased, and this increase is a function of the clinical severity.
TL;DR: It is speculated that T1 alpha protein may modulate or participate in these types of cellular functions in the lung by processes of active ion transport and water fluxes, probably through the aquaporin 1 (channel-forming integral membrane protein [CHIP] 28).
Abstract: T1 alpha is the first marker gene known to be expressed in the adult lung solely by the alveolar type I epithelial cell. Previous studies showed that T1 alpha transcripts are abundant in early rat embryos where they are found in the nervous system and in the foregut and certain of its derivatives including the primitive lung. By mid- to late gestation T1 alpha messenger RNA (mRNA) expression is lost from neural tissues but appears to increase in the lung throughout fetal life. To determine whether the T1 alpha transcripts are translated into protein, especially in early embryos which sometimes express transcripts that are translationally silent, we performed immunohistochemistry on embryos and fetal tissues and analyzed certain tissues by western blotting using a monoclonal antibody against T1 alpha protein. T1 alpha protein is present at all sites that have previously been shown to express the mRNA and at similar developmental stages. As estimated from western blots, T1 alpha protein abundance peaks at about fetal day 16 in the brain and decreases thereafter to a relative level in the adult that is lower than that of the neural tube of the day 13 embryo. Relative protein abundance in the lung is very low, although detectable, on embryonic day 13 but increases slowly until fetal day 20 when there is a dramatic increase. At the time of birth, restriction to the type I cell is not complete and therefore must occur during postnatal lung development. Immunostaining reveals additional sites of expression in fetal and adult rats that had not been clearly visualized in previous in situ hybridization studies. T1 alpha is present in mesonephric tubules and apparently in primitive germ cells but is not detectable in specific cells in the adult kidney, ovary, or testis. However, cells of the choroid plexus of the central nervous system and the ciliary epithelium of the eye express T1 alpha in both fetuses and adults. The well-known functions of these epithelia are to elaborate cerebrospinal fluid and aqueous humor respectively by processes of active ion transport and water fluxes, probably through the aquaporin 1 (channel-forming integral membrane protein [CHIP] 28). We speculate therefore that T1 alpha protein may modulate or participate in these types of cellular functions in the lung.
TL;DR: It appears that cytokines favoring the maintenance of fetal survival mainly belong to the Th2 pathway, whereas the failure of pregnancy rather associates with the predominance of Th1- type cytokines and/or the absence of Th2-type cytokines.
Abstract: There is clear evidence to suggest that the maternal immune system during pregnancy can enhance or inhibit the development of the fetoplacental unit Recent data support the view that some cytokines produced by both T cells and non-T cells (IL-3, GM-CSF, TGF-beta, IL-4, IL-10), favor fetal survival and growth In contrast, other cytokines, such as IFN-gamma, TNF-beta and TNF-alpha, can rather compromise pregnancy Accordingly, we show here that T-cell clones generated from the decidua of women with unexplained recurrent abortion produced significantly lower concentrations of IL-4 than clones derived from the decidua of voluntary abortions or the endometrium of nonpregnant women Thus, despite the complexity of the cytokine network, it appears that cytokines favoring the maintenance of fetal survival mainly belong to the Th2 pathway, whereas the failure of pregnancy rather associates with the predominance of Th1-type cytokines and/or the absence of Th2-type cytokines Interestingly, we also found that, at least in vitro, progesterone promotes the preferential development of Th2-like cells and induces transient IL-4 production by established Th1 cells, whereas relaxin, another corpus luteum-derived hormone, mainly promotes the development of Th1-like cells These data provide an excellent basis for investigating the relationship between the endocrine and the immune system in the regulation of the maternal-fetal interaction
TL;DR: Results suggest that placental ID-III activity is regulated by serum T3, but not by serumT4, and may play a role in the regulation of intraplacental T3 generation.
Abstract: Thyroid hormones are essential for fetal development. T4 can be activated by type I (ID-I) and type II (ID-II) iodothyronine deiodinase or inactivated by type III deiodinase (ID-III). The influence of placental ID-II and ID-III on the regulation of fetal thyroid hormone levels was investigated. Using [125I]T4 and [125I]T3, respectively, ID-II and ID-III activities were measured in homogenates of normal human placentas from 6-43 weeks gestational age and in placentas from five term neonates with a total thyroid hormone synthesis defect. ID-II and ID-III activities related to protein or DNA concentration decreased and total placental ID-III activity increased significantly during pregnancy, whereas the increase in total placental ID-II activity was not significant. Absolute placental ID-II activity was approximately 200 times lower than ID-III activity at all gestational ages. Therefore, fluctuations in ID-II activity were not likely to have a significant influence on fetal thyroid hormone concentrations, but may play a role in the regulation of intraplacental T3 generation. The high ID-III activity most likely influences the thyroid hormone economy of the fetus. Severely hypothyroid newborns showed strongly decreased serum T4 levels, but serum T3 and placental ID-III activities were similar to those in euthyroid newborns. These results suggest that placental ID-III activity is regulated by serum T3, but not by serum T4.
TL;DR: Fetal growth differences among control infants and infants with d-transposition of the great arteries, tetralogy of Fallot, hypoplastic left heart syndrome, and coarctation of the aorta are characterized to suggest that fetal circulatory abnormalities may predict abnormal patterns of fetal growth.
Abstract: This study characterized fetal growth differences among control infants (n= 276) and infants with d-transposition of the great arteries (TGA) (n = 69), tetralogy of Fallot (n = 66), hypoplastic left heart syndrome (n = 51), and coarctation of the aorta (n = 65), thus permitting assessment of competing theories about the relation between these cardiovascular malformations and fetal growth disturbance. Subjects were liveborn singletons without genetic or extra-cardiovascular structural abnormalities sampled from the Baltimore-Washington Infant Study. Multivariate analysis of covariance was performed: birth weight, birth length, newborn head circumference, and two nonlinear functions of these measures were regressed jointly on a diagnostic class variable and covariates. Differences in the vectors of dependent variable means across diagnostic groups were striking (p < 0.0001). Infants with TGA had normal birth weight, but lesser head volume relative to birth weight. Infants with tetralogy of Fallot were smaller in all measured dimensions, but they were shaped normally. Infants with hypoplastic left heart syndrome were smaller in all measured dimensions, and head volume was disproportionately small relative to birth weight. Infants with coarctation of the aorta had lower birth weight, shorter birth length, and greater head volume relative to birth weight. These findings suggest that fetal circulatory abnormalities may predict abnormal patterns of fetal growth.
TL;DR: The role of antibodies to fetal AChR and perhaps other muscle antigens in some cases of AMC are demonstrated and placental transfer of antibodies directed at fetal antigen should be considered as a cause of other recurrent fetal or perinatal disorders.
Abstract: Arthrogryposis multiplex congenita (AMC), characterized by multiple joint contractures developing in utero, results from lack of fetal movement. Some cases are genetically determined, but AMC occasionally complicates pregnancy in patients with myasthenia gravis (MG) suggesting involvement of circulating maternal antibodies. We previously demonstrated antibodies that inhibited the function of fetal acetylcholine receptor (AChR) in one healthy woman with an obstetric history of recurrent AMC. Here we study sera from this woman, from one other with a similar history, and from three (one asymptomatic) whose babies had neonatal MG and AMC. All five maternal sera had high titers of antibodies that inhibited alpha-Bungarotoxin (alpha-BuTx) binding to fetal AChR, and their sera markedly inhibited fetal AChR function with little effect on adult AChR function. Moreover, in a further survey, 3 of 20 sera from anti-AChR negative AMC mothers inhibited fetal AChR function significantly at 1:100 dilution. These results demonstrate the role of antibodies to fetal AChR and perhaps other muscle antigens in some cases of AMC. More generally, they suggest that placental transfer of antibodies directed at fetal antigens should be considered as a cause of other recurrent fetal or perinatal disorders.