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Showing papers on "Fetus published in 1993"


Journal ArticleDOI
TL;DR: This paper shows how fetal undernutrition at different stages of gestation can be linked to these patterns of early growth in babies who are small at birth or during infancy.

2,594 citations


Journal ArticleDOI
David Haig1
TL;DR: The placenta is able to release hormones and other substances directly into the maternal circulation as discussed by the authors, which can be interpreted as an attempt by a poorly nourished fetus to increase its supply of nutrients by increasing the resistance of its mother's peripheral circulation.
Abstract: Pregnancy has commonly been viewed as a cooperative interaction between a mother and her fetus. The effects of natural selection on genes expressed in fetuses, however, may be opposed by the effects of natural selection on genes expressed in mothers. In this sense, a genetic conflict can be said to exist between maternal and fetal genes. Fetal genes will be selected to increase the transfer of nutrients to their fetus, and maternal genes will be selected to limit transfers in excess of some maternal optimum. Thus a process of evolutionary escalation is predicted in which fetal actions are opposed by maternal countermeasures. The phenomenon of genomic imprinting means that a similar conflict exists within fetal cells between genes that are expressed when maternally derived, and genes that are expressed when paternally derived. During implantation, fetally derived cells (trophoblast) invade the maternal endometrium and remodel the endometrial spiral arteries into low-resistance vessels that are unable to constrict. This invasion has three consequences. First, the fetus gains direct access to its mother's arterial blood. Therefore, a mother cannot reduce the nutrient content of blood reaching the placenta without reducing the nutrient supply to her own tissues. Second, the volume of blood reaching the placenta becomes largely independent of control by the local maternal vasculature. Third, the placenta is able to release hormones and other substances directly into the maternal circulation. Placental hormones, including human chorionic gonadotropin (hCG) and human placental lactogen (hPL), are predicted to manipulate maternal physiology for fetal benefit. For example, hPL is proposed to act on maternal prolactin receptors to increase maternal resistance to insulin. If unopposed, the effect of hPL would be to maintain higher blood glucose levels for longer periods after meals. This action, however, is countered by increased maternal production of insulin. Gestational diabetes develops if the mother is unable to mount an adequate response to fetal manipulation. Similarly, fetal genes are predicted to enhance the flow of maternal blood through the placenta by increasing maternal blood pressure. Preeclampsia can be interpreted as an attempt by a poorly nourished fetus to increase its supply of nutrients by increasing the resistance of its mother's peripheral circulation.

1,041 citations


Journal ArticleDOI
TL;DR: It was found that rat placental 11 beta-OHSD activity correlated positively with term fetal weight and negatively with placental weight, and offspring of rats treated during pregnancy with dexamethasone had lower birthweights and higher blood pressure when adult than did offspring of control rats.

868 citations



Journal ArticleDOI
TL;DR: In patients with beta-hemoglobinopathies butyrate, a natural fatty acid, can significantly and rapidly increase fetal-globin production to levels that can ameliorate beta- globin disorders.
Abstract: Background Fetal-globin (γ-globin) chains inhibit the polymerization of hemoglobin S (sickle hemoglobin) and can functionally substitute for the β-globin chains that are defective or absent in patients with the β-thalassemias. Identifying safe mechanisms to stimulate fetal-hemoglobin production is therefore of great interest. Previous studies have shown that administering butyrate selectively stimulates the promoter of the human fetal-globin gene and leads to increases in γ-globin-gene expression in the developing fetus, cultured cells, and animal models. Methods To determine whether butyrate can stimulate fetal-globin production in humans, we treated three patients (3 to 13 years old) with sickle cell anemia and three patients (7 to 27 years old) with β-thalassemia syndromes with a short course of intravenous infusions of arginine butyrate. The drug was infused continuously for either two or three weeks; the initial dose was 500 mg per kilogram of body weight per day. Globin-chain ratios, proportions of ...

467 citations


Journal ArticleDOI
TL;DR: The umbilical cord plasma CRH level is extremely elevated in growth-retarded fetuses compared to that in normal fetuses and may modulate fetal pituitary-adrenal function in high risk pregnancies.
Abstract: CRH is synthesized in the hypothalamus and released in response to stress into the portal hypophyseal blood; an additional site of synthesis, the placenta, is present only during pregnancy. Placental CRH is released into the maternal and fetal circulation during human pregnancy, and we hypothesized that the chronic fetal stress associated with fetal growth retardation may stimulate placental CRH release. We measured plasma CRH concentrations in the umbilical cord blood of 28 growth-retarded fetuses and 28 normally grown fetuses matched for gestational age and mode of delivery. Plasma ACTH, dehydroepiandrosterone sulfate (DHEAS), and cortisol were also measured in the umbilical cord samples to determine if CRH levels were correlated with levels of pituitary and adrenal hormones. The mean umbilical cord plasma CRH level in the growth-retarded fetuses was 206 +/- 25.8 pmol/L, which was significantly higher than that in the normally grown fetuses matched for gestational age, presence or absence of labor, and mode of delivery (49.4 +/- 16.7 pmol/L; P < 0.01). The mean plasma ACTH level in the growth-retarded fetuses (5.7 +/- 1.2 pmol/L) was significantly higher than that in the normally grown fetuses (3.3 +/- 0.7 pmol/L; P < 0.05). The mean cortisol concentration in the growth-retarded fetuses was 260 +/- 32.5 nmol/L, and that in the normally grown fetuses was 220 +/- 40 nmol/L. The mean DHEAS level was significantly lower in the growth-retarded fetuses (4.8 +/- 0.6 mumol/L) than that in the normally grown fetuses (7.7 +/- 0.6 mumol/L; P < 0.001). There was a significant correlation between umbilical cord plasma CRH and both ACTH and cortisol concentrations as well as a significant negative correlation between CRH and DHEAS levels in the growth-retarded fetuses. The umbilical cord plasma CRH level is extremely elevated in growth-retarded fetuses compared to that in normal fetuses. Placental CRH, like hypothalamic CRH, may be stimulated in conditions of chronic stress and may modulate fetal pituitary-adrenal function in high risk pregnancies.

330 citations


Journal Article
TL;DR: The study revealed that leptospirosis was an important cause of bacterial abortion in mares, and that infection by a nocardioform actinomycete was anImportant cause of chronic placentitis.
Abstract: Pathology case records of 3,514 aborted fetuses, stillborn foals, or foals that died < 24 hours after birth and of 13 placentas from mares whose foals were weak or unthrifty at birth were reviewed to determine the cause of abortion, death, or illness Fetoplacental infection caused by bacteria (n = 628), equine herpesvirus (143), fungi (61), or placentitis (351), in which an etiologic agent could not be defined, was the most common diagnosis Complications of birth, including neonatal asphyxia, dystocia, or trauma, were the second most common cause of mortality and were diagnosed in 19% of the cases (679) Other common diagnoses were placental edema or premature separation of placenta (249), development of twins (221), contracted foal syndrome (188), other congenital anomalies (160), and umbilical cord abnormalities (121) Less common conditions were placental villous atrophy or body pregnancy (81), fetal diarrhea syndrome (34), and neoplasms or miscellaneous conditions (26) A diagnosis was not established in 16% of the cases seen (585) The study revealed that leptospirosis (78) was an important cause of bacterial abortion in mares, and that infection by a nocardioform actinomycete (45) was an important cause of chronic placentitis

248 citations


Journal ArticleDOI
TL;DR: The present data suggest that d‐aspartate and d‐serine might play a pivotal role in cerebral development and functions that are related to the NMDA receptor.
Abstract: We have analyzed free chiral amino acids (aspartate and serine) in the human frontal cortex at different ontogenic stages (from 14 weeks of gestation to 101 years of age) by HPLC with fluorometric detection after derivatization with N-tert-butyl-oxycarbonyl-L-cysteine and o-phthaldialdehyde. Exceptionally high levels of free D-aspartate and D-serine were demonstrated in the fetal cortex at gestational week 14. The ratios of D-aspartate and of D-serine to the total corresponding amino acids were also high, at 0.63 and 0.27, respectively. The concentration of D-aspartate dramatically decreased to a trace level by gestational week 41 and then remained very low during all postnatal stages. In contrast, the frontal tip contained persistently high levels of D-serine throughout embryonic and postnatal life, whereas the D-amino acid content in adolescents and aged individuals was about half of that in the fetuses. Because D-aspartate and D-serine are known to have selective actions at the NMDA-type excitatory amino acid receptor, the present data suggest that these D-amino acids might play a pivotal role in cerebral development and functions that are related to the NMDA receptor.

247 citations


Journal ArticleDOI
TL;DR: A complex pattern of expression suggests that V EGF is involved in angiogenesis on both maternal and fetal sides of the placenta and that macrophages are the primary source of VEGF.
Abstract: Implantation and growth of the placenta requires extensive angiogenesis to establish the vascular structures involved in exchange. Failure to establish adequate blood supply to the fetus may have serious clinical consequences such as intrauterine growth retardation. Vascular endothelial cell growth factor (VEGF) is a recently identified growth factor with significant angiogenic properties. We have demonstrated the presence of four species of mRNA encoding VEGF in both first trimester and term placenta. In situ hybridization was used to localize the sites of expression of VEGF mRNA in these tissues. VEGF expression was seen in villous trophoblast in the first trimester and in extravillous trophoblast at term, and in both fetal macrophages within the villi and maternal macrophages in the decidua. Glandular epithelium in maternal decidua also expressed VEGF mRNA. The strongest site of expression was in maternal macrophages adjacent to Nitabuch's stria, a zone of necrosis at the site of implantation. This complex pattern of expression suggests that VEGF is involved in angiogenesis on both maternal and fetal sides of the placenta and that macrophages are the primary source of VEGF. However, VEGF may also play a role in term placenta, when extensive angiogenesis has diminished, possibly regulating vascular permeability.

234 citations


Journal ArticleDOI
TL;DR: Results show that maternal thyroxine can cross the placental barrier as early as the second month of pregnancy, raising the possibility that the increase in maternal T4 occurring during the first trimester may be functionally important for the developing embryo, when its thyroid is not yet functioning.
Abstract: Transfer of maternal thyroxine (T4) to the human fetus near term has recently been demonstrated. We investigated whether maternal thyroid hormone is available to the conceptus during the first trimester of pregnancy as well. Transvaginal ultrasound-guided puncture of the embryonic cavities was performed during the first trimester of pregnancy to obtain coelomic fluid between 6 and 11 weeks, and amniotic fluid between 8 and 11 weeks of pregnancy. T4 was found in coelomic fluid with mean values (+/- SEM) being 961 +/- 193 pmol T4/L (747 +/- 150 pg/mL). Concentrations increased both with gestational age and with rising maternal serum T4. Concentrations of 3,5,3'-triiodothyronine (T3) were at least 30 times lower, and those of 3,3',5'-triiodothyronine (rT3) four times higher, than coelomic fluid T4. Thyroxine and rT3 in amniotic fluid (8-11 weeks) were markedly lower than in the coelomic fluid, and T3 was undetectable. These results show that maternal thyroxine can cross the placental barrier as early as the second month of pregnancy. T4 from the coelomic fluid may reach the embryo via the yolk sac. This finding raises the possibility that the increase in maternal T4 occurring during the first trimester may be functionally important for the developing embryo, when its thyroid is not yet functioning.

234 citations


Journal ArticleDOI
TL;DR: Insulin, insulin- like growth factors I and II and insulin are all related to fetal growth and weight gain, and insulin-like growth factor-I correlates best with birth weight.

Journal ArticleDOI
TL;DR: The present study suggests that fetal nucleated cells increase in maternal peripheral blood with advancing gestation, from less than 1 in 100,000ucleated cells in the first trimester to around 1 in 10,000 at term, much lower than those reported by cytological methods.
Abstract: To determine the frequency of fetal nucleated cells in maternal peripheral blood during different stages of pregnancy, 50 primigravidas were investigated by determining the frequency of cells with the Y chromosome using fluorescence in situ hybridization (FISH) of Y-specific repetitive sequences of the DYZ1 family. Polymerase chain reaction (PCR) amplifying the same part of the DYZ1 used as the probe in FISH and a single-copy Y-specific fragment was also carried out for genomic DNA from the same samples. Cells with the hybridization signal were detected by FISH at and after 15 weeks of pregnancy in all pregnant women who gave birth to boys. The ratio of cells with the signal to those without the signal ranged from 1 in 144,000 to 1 in 4,000 with a tendency to increase as the pregnancy advanced. The frequency of fetal cells estimated by the PCR experiments was significantly and positively correlated with that found by FISH. The present study suggests that fetal nucleated cells increase in maternal peripheral blood with advancing gestation, from less than 1 in 100,000 nucleated cells in the first trimester to around 1 in 10,000 at term. These frequencies were much lower than those reported by cytological methods.

Journal ArticleDOI
TL;DR: A safe method of determining fetal RhD type early in pregnancy would eliminate the risks to an RhD-negative fetus of fetal-blood sampling or serial amniocenteses.
Abstract: Background. An RhD-negative woman whose partner is heterozygous may have preexisting anti-RhD antibodies that may or may not affect a subsequent fetus, depending on whether it is heterozygous. A safe method of determining fetal RhD type early in pregnancy would eliminate the risks to an RhD-negative fetus of fetal-blood sampling or serial amniocenteses.

Journal ArticleDOI
TL;DR: It is concluded that alpha rENaC is expressed in mature fetal and adult alveolar epithelium and that it is influenced by hormones known to alter maturation of the fetal lung.
Abstract: The adult mature fetal, but not immature fetal, lung is capable of actively transporting Na+ from the alveolar space. The reason for the impaired Na+ transport in the immature lung is not known; however, the apical membrane Na+ channel is the rate-limiting step for epithelial Na+ transport. This study determined whether transcripts coding for the adult rat colonic epithelial Na+ channel (alpha rENaC) were present in the fetal and adult lung and whether they were developmentally regulated. Similarly sized alpha rENaC transcripts were identified in RNA isolated from fetal and adult whole rat lung, primary cultures of fetal and adult alveolar epithelium, and adult rat whole kidneys, suggesting that the lung alpha rENaC is a similar transcript to that found in the salt-deprived rat colonic epithelium. There were low mRNA levels in 17- to 18-day gestational age (GA) fetal lungs and epithelium (term GA = 22 days), but these levels increased markedly during the saccular stage of lung development (20 days GA) and remained high in adult lungs. The combined administration of thyroid-releasing hormone and dexamethasone to pregnant rats between 16 and 18 days GA induced the expression of lung alpha rENaC in their fetuses. We conclude that alpha rENaC is expressed in mature fetal and adult alveolar epithelium and that it is influenced by hormones known to alter maturation of the fetal lung.

Journal ArticleDOI
Gerard N. Burrow1
TL;DR: There is a constant hormonal interplay among fetus, mother, and placenta during pregnancy, and human CG concentrations rapidly increase ensuring a supply of progesterone necessary for the maintenance of pregnancy before placental production is assured.
Abstract: I. Physiology of Pregnancy FOLLOWING implantation, a series of hormonal and metabolic events occur that help to shield the fetus from unfavorable changes in the maternal environment. From an endocrine standpoint these changes are controlled by steroid production in the fetal adrenals and gonads and in the placenta, as well as polypeptide hormones produced by the fetal pituitary and placenta. There is a constant hormonal interplay among fetus, mother, and placenta during pregnancy. Human CG (hCG) concentrations rapidly increase ensuring a supply of progesterone necessary for the maintenance of pregnancy before placental production is assured. These endocrine changes, including chorionic somatomammotropin production, also alter fuel metabolism, perhaps ensuring substrate for fetal growth (1). Serum PRL levels increase as do levels of CRH as a result of pituitary and hypothalamic stimulation (2). Maternal blood volume increases by 40% above nonpregnant values due to hormonal changes and venous distension tha...

Journal ArticleDOI
TL;DR: Anti-Mullerian hormone is a reliable marker for the presence of functional testicular tissue and, as such, may be helpful for the diagnosis of fetal sex, particularly in the absence of sex chromosome abnormalities.

Journal ArticleDOI
TL;DR: The use of indomethacin should be restricted to gestational ages of < 32 weeks, and in multiple gestations each fetus should be evaluated by echocardiography, because the ductal response may vary between individual fetuses.

Journal ArticleDOI
TL;DR: Hou et al. as mentioned in this paper showed that ERs are present in the 10-day mouse fetus, possibly in the developing ambisexual reproductive tract, and showed that the pattern of expression of ER between implantation and the development of the reproductive tract may be the same in male and female mice.
Abstract: To date, there is no conclusive evidence that ERs are present in preimplantation embryos. There are reports that estrogen is made by the rabbit blastocyst (61), and estrogens have been used to induce implantation in mice (62), but whether estrogens act through ERs in the embryo or in the maternal uterus is not known. ERs may be present in early embryos, but if so, levels are below the methods of detection used thus far. Perhaps with more sensitive immunodetection methods, it may be possible to detect ERs in embryos if they are present. Using PCR, messenger RNA for ER has been detected as early as the oocyte stage in mouse embryos (Q. Hou and J. Gorski, unpublished results). This was confirmed recently by Wu et al. (83a). Figure 7 shows a model for the pattern of ER expression in the developing mouse fetus based on the various reports discussed in this review. ERs are present in the 10-day mouse fetus, possibly in the developing ambisexual reproductive tract. Analysis of seven individual 10-day-old fetuses taken from the same litter showed similar levels of an immunostained protein the size of the ER in each fetus (57). The pattern of expression of ER between implantation and the development of the reproductive tract may be the same in male and female mice. Estrogen, acting through ERs, may be one factor (of many) that determines which cells are destined to be part of the indifferent reproductive tract. We were not able to isolate fetal mouse reproductive tracts at an indifferent stage (day 10) due to their very small size. One way to study ER in the indifferent reproductive tract would be to examine these tissues in a larger animal, such as the bovine, using similar immunodetection methods. The distribution of ER in the fetal mouse reproductive tract on fetal days 13 (before sexual differentiation) and 15 (initiation of sexual differentiation) is similar in males and females (71, 72). Thus, estrogen does not appear to be responsible for the initiation of sexual differentiation. Early experiments by Jost (41) showed that removal of the gonad from male or female rabbit fetuses resulted in the female phenotype, which lent weight to the hypothesis that ovarian hormones are not critical in the development of the female phenotype, whereas testicular hormones are essential for the development of the male phenotype.(ABSTRACT TRUNCATED AT 400 WORDS)

Journal ArticleDOI
TL;DR: Fetal therapy can now be considered for otherwise fatal space-occupying intrathoracic lesions in the fetus for congenital cystic adenomatoid malformation of the lung.

Journal ArticleDOI
TL;DR: It is concluded that the natural history of prenatally diagnosed fetal lung masses is highly variable and a huge mass associated with fetal hydrops has a dismal outcome.

Journal ArticleDOI
TL;DR: The use of the Magnetic Activated Cell Sorter for enriching fetal nucleated erythrocytes was investigated and the potential of the method for clinical practice was confirmed by a pilot prospective study of fetal sex in women referred for amniocentesis between 13 and 17 weeks of gestation.
Abstract: Fetal nucleated cells in the maternal circulation constitute a potential source of cells for the non-invasive prenatal diagnosis of fetal genetic abnormalities. We have investigated the use of the Magnetic Activated Cell Sorter (MACS) for enriching fetal nucleated erythrocytes. Mouse monoclonal antibodies specific for CD45 and CD32 were used to deplete leucocytes from maternal blood using MACS sorting, thus enriching for fetal nucleated erythrocytes which do not express either of these antigens. However, significant maternal contamination was present even after MACS enrichment preventing the accurate analysis of fetal cells by interphase fluorescence in situ hybridisation (FISH). To overcome this problem, we used simultaneous immunophenotyping of cells with the mouse antifetal haemoglobin antibody, UCH gamma, combined with FISH analysis using chromosome X and Y specific DNA probes. This approach enables selective FISH analysis of fetal cells within an excess of maternal cells. Furthermore, we have confirmed the potential of the method for clinical practice by a pilot prospective study of fetal sex in women referred for amniocentesis between 13 and 17 weeks of gestation.

Journal ArticleDOI
TL;DR: Since these cytokines are abortifacients in vivo and have detrimental effects on the placenta, and hence on fetal development and survival, the demonstration of enhanced expression of these deleterious cytokines may give insight into the mechanisms involved in immunologically mediated spontaneous abortions.
Abstract: It is clear that the immune system and the reproductive system interact with and influence each other and that the immune system can have positive and negative regulatory effects on the outcome of pregnancy. The discovery of murine models of immunologically mediated spontaneous fetal resorptions has proved to be very useful for the study of immunological influences on pregnancy. In an attempt to elucidate the mechanisms underlying pregnancy impairment in one such "natural" model of pregnancy loss, we compared the expression of the cytokines tumor necrosis factor alpha, interferon tau, and interleukin-2 in placental tissue from a resorption-prone strain combination with the expression from a normal combination. We found significantly enhanced expression of these three cytokines in placentas from the resorption-prone combination using dot-blot hybridization and Northern hybridizations. Since these cytokines are abortifacients in vivo and have detrimental effects on the placenta, and hence on fetal development and survival, our demonstration of enhanced expression of these deleterious cytokines may give insight into the mechanisms involved in immunologically mediated spontaneous abortions.

Journal ArticleDOI
TL;DR: Gender prediction accuracy was used as a measure of fetal cell separation and successful isolation of fetal cells was defined as detection of Y chromosomal sequences in maternal blood from women carrying male fetuses, with absence of Y sequences when female fetuses were carried.
Abstract: Fetal nucleated erythrocytes (NRBC) in maternal blood are a non-invasive source of fetal DNA for prenatal genetic screening. We compared the effectiveness of three monoclonal antibodies for the separation of fetal cells from maternal blood by flow sorting. Mononuclear blood cells from 49 healthy pregnant women were incubated with antibody to CD 71, CD 36, and/or glycophorin A (GPA), employed singly or in combination with each other. These monoclonal antibodies recognize surface antigens on haematopoietic precursor cells. Successful isolation of fetal cells was defined as detection of Y chromosomal sequences in maternal blood from women carrying male fetuses, with absence of Y sequences when female fetuses were carried. Thus, gender prediction accuracy was used as a measure of fetal cell separation. Using anti-CD 71 to isolate fetal cells, gender prediction was 57 per cent correct; with anti-CD 36, it was 88 per cent correct. Anti-GPA, an erythrocyte-specific antigen, used alone or in combination with anti-CD 71 or 36, improved gender prediction to 100 per cent. We conclude that antibody to GPA improves the retrieval of fetal NRBC from maternal blood, permitting genetic analysis by the polymerase chain reaction.

Journal ArticleDOI
TL;DR: It is demonstrated that the severe ACA-induced gestational failure results from an impairment of implantation and suggest that the ACA may react directly with the preimplantation embryos.
Abstract: The antiphospholipid syndrome is characterized by thrombocytopenia, thrombosis, and recurrent fetal loss in association with anti-cardiolipin antibodies (ACAs) or lupus anti-coagulants. However, the causal role of these antibodies in the disease and the mechanisms by which the ACA may induce the syndrome are not clear. Recently, we have established an experimental mouse antiphospholipid syndrome induced by the mouse IgM monoclonal ACA designated 2C4C2. In the present study, we focused on the effects of immunization with the monoclonal ACA 2C4C2 on the outcome of pregnancies in BALB/c female mice. Four weeks after active immunization with the monoclonal ACA, a severe gestational failure with low pregnancy rates, low number of fetuses, and a high rate of resorptions was observed. Moreover, embryos obtained from the ACA-immunized females on day 3.5 of pregnancy were severely impaired, demonstrating developmental delay and abnormal morphology. These abnormal embryos failed also to develop in an in vitro implantation model. Furthermore, specific binding of the 2C4C2 ACA to the trophectoderm cell lineage of in vitro implanting normal embryos was observed. Thus, our studies demonstrate that the severe ACA-induced gestational failure results from an impairment of implantation and suggest that the ACA may react directly with the preimplantation embryos.

Journal ArticleDOI
TL;DR: The expression of NGF, brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) mRNAs was examined in whole rat embryos and in the heart and great vessels of postnatal and adult rats, using in situ hybridization of cRNA probes.
Abstract: The expression of NGF, brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) mRNAs was examined in whole rat embryos and in the heart and great vessels of postnatal and adult rats, using in situ hybridization of cRNA probes. The patterns of expression were correlated with innervation patterns as revealed by immunostaining for neural cell adhesion molecule (NCAM) and with the HNK-1 antibody, which demonstrates derivatives of the neural crest. The patterns of neurotrophin mRNA localization were different from those of mRNAs for the low-molecular-weight NGF receptor. Hybridization indicating the presence of mRNAs for all three neurotrophins is particularly prominent within the tunica media of the aorta, pulmonary, and other major elastic arteries of the thorax and abdomen and is first observed on embryonic day 13 (E13) when innervation is being established and rises to maximum by E15. In the fetus, there is little or no detectable expression in the CNS or PNS. NT-3 expression in the vessels is relatively constant and high from embryonic to adult stages, while levels of BDNF increase and those of NGF decrease over the same time course. During the fetal period, hybridization in the heart is absent. In the postnatal period, additional label becomes detectable in the coronary arteries but not in the walls of the atria or ventricles, other than at the base of the aorta and pulmonary trunk.(ABSTRACT TRUNCATED AT 250 WORDS)

Journal ArticleDOI
TL;DR: It is suggested that data are compatible with the presence of a zinc-deficiency syndrome in pregnancy, which includes increased maternal morbidity, abnormal taste sensations, abnormally short or prolonged gestations, inefficient labor, atonic bleeding, and increased risks to the fetus such as malformations, growth retardation, prematurity, postmaturity, and perinatal death.
Abstract: Zinc is present in and indispensable to all forms of life. Zinc is essential for the normal growth of human beings, and zinc proteins have been shown to be involved in the transcription and translation of the genetic material. Zinc deficiency has been incriminated in infertility, abortions, malformations, fetal intrauterine growth retardation, premature and postmature births, perinatal death, and abnormal deliveries with dystocia and placental ablation. Risk groups for developing zinc deficiency, which in turn might modify the expression of the underlying disease, are found among those with insufficient food intake, especially in protein malnutrition; abnormal mucosal uptake, as in celiac disease; abnormal intestinal losses, as in steatorrhea and inflammatory bowel disease; abnormal renal excretion, as in diabetes with insufficient metabolic control; alcoholism; and treatment with diuretic drugs. Zinc deficiency could be identified by means of fasting serum or plasma samples or the more laborious estimation of zinc in leucocytes or monocytes if sampling and handling is carefully performed and if stressful situations and acute-phase reactions as fever, delivery, or abortion are avoided. Zinc therapy in identified low-zinc groups has given favorable results and has reduced the frequencies of premature birth, placental ablation, perinatal death, and postmaturity. It is suggested, as we did in 1980, that these data are compatible with the presence of a zinc-deficiency syndrome in pregnancy, which includes increased maternal morbidity, abnormal taste sensations, abnormally short or prolonged gestations, inefficient labor, atonic bleeding, and increased risks to the fetus such as malformations, growth retardation, prematurity, postmaturity, and perinatal death.

Journal ArticleDOI
TL;DR: In this paper, the in situ localization of key steroidogenic enzymes in adrenal gland sections from midgestation (17-24 weeks) human fetuses and late gestation (130-142 days; term = 165 days) rhesus monkey fetuses was examined.
Abstract: We examined the in situ localization of key steroidogenic enzymes in adrenal gland sections from midgestation (17-24 weeks) human fetuses and late gestation (130-142 days; term = 165 days) rhesus monkey fetuses. The rhesus monkey fetal adrenals were used as a model for the late gestation human fetal adrenal. The enzymes examined were cytochrome P450 cholesterol side-chain cleavage (P450scc), cytochrome P450 17 alpha-hydroxylase/17,20-lyase (P450c17), and 3 beta-hydroxysteroid dehydrogenase/isomerase (3 beta HSD). In human fetal adrenals, P450scc and P450c17 proteins and mRNAs were detected only in fetal zone (innermost cortical zone) and transitional zone (between the fetal and definitive zone) cells, not in definitive zone cells. Expression of 3 beta HSD was not detected in any cortical zone cells in midgestation human fetal adrenals. In rhesus monkey fetal adrenals, a similar pattern of P450scc and P450c17 expression was observed in the fetal and transitional zones. In the definitive zone cells of rhesu...

Journal ArticleDOI
TL;DR: IL-3 may be effective in prevention of recurrent fetal loss in APLS and the thrombocytopenia associated with the experimental APLS was also corrected following lymphokine administration.
Abstract: Antiphospholipid antibodies are strongly associated with arterial and venous thrombosis and with fetal loss. Recently an experimental model for antiphospholipid syndrome (APLS) was established in our laboratory. In this model, mice are immunized passively or actively with anticardiolipin antibodies and acquire the syndrome, which is characterized by prolonged activated partial thromboplastin time (APTT), thrombocytopenia, low fecundity rate, and fetal loss. In a normal process of pregnancy, lymphokines affect fetal implantation and development. Cytokines from the colony stimulating factor family, like GM-CSF and IL-3, were shown to be positive signals for implantation and to promote placental development and fetal growth. Given our preliminary findings of low IL-3 in mice with APLS and the efficacy of IL-3 in preventing fetal loss in a strain of mice prone to fetal resorption, our aim in the present study was to examine the effect of murine recombinant IL-3 (mrIL-3) on pregnant mice induced with experimental APLS. Mice were passively transfused to the tail vein, 24 h following mating, with anticardiolipin antibodies. The mice were divided into two groups: one group was injected intraperitoneally with mrIL-3 on days 6.5, 8.5, and 10.5 after mating, while the control group was injected with PBS. When the mice were killed on day 15 of pregnancy a 32% +/- 4.2 resorption rate was observed in the anti-cardiolipin-immunized group, which was reduced to 4% +/- 0.3 following treatment with mrIL-3. The thrombocytopenia associated with the experimental APLS was also corrected following lymphokine administration. IL-3 may be effective in prevention of recurrent fetal loss in APLS.

Journal Article
TL;DR: An understanding of fetal hemodynamics and the acute and chronic changes that occur with transition to the newborn circulation are important for the care of normal newborns and are crucial to the recognition, diagnosis, and management of the newborn with significant congenital heart disease.

01 Jan 1993
TL;DR: The data suggest that early in gestation, cortisol is not produced by the human fetal adrenal cortex in vivo (because it does not express 3 beta HSD), whereas androgen production occurs in the transitional and fetal zones (which express P450scc and P450c17).
Abstract: We examined the in situ localization of key steroidogenic enzymes in adrenal gland sections from midgestation (17-24 weeks) human fetuses and late gestation (130-142 days; term = 165 days) rhesus monkey fetuses. The rhesus monkey fetal adrenals were used as a model for the late gestation human fetal adrenal. The enzymes examined were cytochrome P450 cholesterol side-chain cleavage (P45Oscc), cytochrome P450 17ol-hydroxylase/l7,20-lyase (P45Oc17), and 3fl-hydroxysteroid dehydrogenase/isomerase (BPHSD). In human fetal adrenals, P45Oscc and P45Oc17 proteins and mRNAs were detected only in fetal zone (innermost cortical zone) and transitional zone (between the fetal and definitive zone) cells, not in definitive zone cells. Expression of 3PHSD was not detected in any cortical zone cells in midgestation human fetal adrenals. In rhesus monkey fetal adrenals, a similar pattern of P45Oscc and P45Oc17 expression was observed in the fetal and transitional zones. In the definitive zone cells of rhesus monkey fetal adrenals, expression of both P45Oscc and 3pHSD was detected. In addition, low levels of 3PHSD expression could be detected in some transitional zone cells. P45Oc17 expression was lacking in definitive zone cells from rhesus monkey fetal adrenals. These data suggest that early in gestation, cortisol is not produced by the human fetal adrenal cortex in vivo (because it does not express 3PHSD), whereas androgen production occurs in the transitional and fetal zones (which express P45Oscc and P45Oc17). Later in gestation, the definitive zone may produce mineralocorticoids (because it expresses P45Oscc and 3PHSD, but lacks P45Oc17), and the transitional zone may produce glucocorticoids (it expresses P45Oscc, P45Oc17, and 3flHSD), whereas the fetal zone continues to produce androgens. Thus, late in gestation the functional zonation of the human fetal adrenal cortex may be similar to that of the adult, with the definitive zone being analogous to the nascent zona glomerulosa, the transitional zone analogous to the zona fasciculata, and the fetal zone analogous to the zona reticularis. (J Clin