Showing papers on "Fetus published in 2004"

Regulatory T cells mediate maternal tolerance to the fetus.

Abstract: Pregnancy constitutes a major challenge to the maternal immune system, as it has to tolerate the persistence of paternal alloantigen Although localized mechanisms contribute to fetal evasion from immune attack, maternal alloreactive lymphocytes persist We demonstrate here an alloantigen-independent, systemic expansion of the maternal CD25+ T cell pool during pregnancy and show that this population contains dominant regulatory T cell activity In addition to their function in suppressing autoimmune responses, maternal regulatory T cells suppressed an aggressive allogeneic response directed against the fetus Their absence led to a failure of gestation due to immunological rejection of the fetus

Isolation of Mesenchymal Stem Cells of Fetal or Maternal Origin from Human Placenta

Abstract: Recently we reported that second-trimester amniotic fluid (AF) is an abundant source of fetal mesenchymal stem cells (MSCs). In this study, we analyze the origin of these MSCs and the presence of MSCs in human-term AF. In addition, different parts of the human placenta were studied for the presence of either fetal or maternal MSCs. We compared the phenotype and growth characteristics of MSCs derived from AF and placenta. Cells from human second-trimester (mean gestational age, 19(+2) [standard deviation, +/- 1(+3)] weeks, n = 10) and term third-trimester (mean gestational age, 38(+4) [standard deviation, +/- 1] weeks, n = 10) AF, amnion, decidua basalis, and decidua parietalis were cultured in M199 medium supplemented with 10% fetal calf serum and endothelial cell growth factor. Cultured cells were immunophenotypically characterized, the adipogenic and osteogenic differentiation capacity was tested, and the growth kinetics were analyzed. The origin of fetal and maternal cells was determined by molecular human leukocyte antigen typing. We successfully isolated MSCs from second-trimester AF, amnion, and decidua basalis as well as term amnion, decidua parietalis, and decidua basalis. In contrast, MSCs were cultured from only 2 out of 10 term AF samples. The phenotype of MSCs cultured from different fetal and maternal parts of the placenta was comparable. Maternal MSCs from second-trimester and term decidua basalis and parietalis showed a significantly higher expansion capacity than that of MSCs from adult bone marrow (p < .05). Our results indicate that both fetal and maternal MSCs can be isolated from the human placenta. Amnion is a novel source of fetal MSCs, likely contributing to the presence of MSCs in AF. Decidua basalis and decidua parietalis are sources for maternal MSCs. The expansion potency from both fetal and maternal placenta-derived MSCs was higher compared with adult bone marrow-derived MSCs.

Role of thyroid hormone during early brain development.

Abstract: The present comments are restricted to the role of maternal thyroid hormone on early brain development, and are based mostly on information presently available for the human fetal brain. It emphasizes that maternal hypothyroxinemia - defined as thyroxine (T4) concentrations that are low for the stage of pregnancy - is potentially damaging for neurodevelopment of the fetus throughout pregnancy, but especially so before midgestation, as the mother is then the only source of T4 for the developing brain. Despite a highly efficient uterine-placental 'barrier' to their transfer, very small amounts of T4 and triiodothyronine (T3) of maternal origin are present in the fetal compartment by 4 weeks after conception, with T4 increasing steadily thereafter. A major proportion of T4 in fetal fluids is not protein-bound: the 'free' T4 (FT4) available to fetal tissues is determined by the maternal serum T4, and reaches concentrations known to be of biological significance in adults. Despite very low T3 and 'free' T3 (FT3) in fetal fluids, the T3 generated locally from T4 in the cerebral cortex reaches adult concentrations by midgestation, and is partly bound to its nuclear receptor. Experimental results in the rat strongly support the conclusion that thyroid hormone is already required for normal corticogenesis very early in pregnancy. The first trimester surge of maternal FT4 is proposed as a biologically relevant event controlled by the conceptus to ensure its developing cerebral cortex is provided with the necessary amounts of substrate for the local generation of adequate amounts of T3 for binding to its nuclear receptor. Women unable to increase their production of T4 early in pregnancy would constitute a population at risk for neurological disabilities in their children. As mild-moderate iodine deficiency is still the most widespread cause of maternal hypothyroxinemia in Western societies, the birth of many children with learning disabilities may already be preventable by advising women to take iodine supplements as soon as pregnancy starts, or earlier if possible.

Drug transfer and metabolism by the human placenta

Abstract: The major function of the placenta is to transfer nutrients and oxygen from the mother to the foetus and to assist in the removal of waste products from the foetus to the mother. In addition, it plays an important role in the synthesis of hormones, peptides and steroids that are vital for a successful pregnancy. The placenta provides a link between the circulations of two distinct individuals but also acts as a barrier to protect the foetus from xenobiotics in the maternal blood. However, the impression that the placenta forms an impenetrable obstacle against most drugs is now widely regarded as false. It has been shown that that nearly all drugs that are administered during pregnancy will enter, to some degree, the circulation of the foetus via passive diffusion. In addition, some drugs are pumped across the placenta by various active transporters located on both the fetal and maternal side of the trophoblast layer. It is only in recent years that the impact of active transporters such as P-glycoprotein on the disposition of drugs has been demonstrated. Facilitated diffusion appears to be a minor transfer mechanism for some drugs, and pinocytosis and phagocytosis are considered too slow to have any significant effect on fetal drug concentrations. The extent to which drugs cross the placenta is also modulated by the actions of placental phase I and II drug-metabolising enzymes, which are present at levels that fluctuate throughout gestation. Cytochrome P450 (CYP) enzymes in particular have been well characterised in the placenta at the level of mRNA, protein, and enzyme activity. CYP1A1, 2E1, 3A4, 3A5, 3A7 and 4B1 have been detected in the term placenta. While much less is known about phase II enzymes in the placenta, some enzymes, in particular uridine diphosphate glucuronosyltransferases, have been detected and shown to have specific activity towards marker substrates, suggesting a significant role of this enzyme in placental drug detoxification. The increasing experimental data on placental drug transfer has enabled clinicians to make better informed decisions about which drugs significantly cross the placenta and develop dosage regimens that minimise fetal exposure to potentially toxic concentrations. Indeed, the foetus has now become the object of intended drug treatment. Extensive research on the placental transfer of drugs such as digoxin and zidovudine has assisted with the safe treatment of the foetus with these drugs in utero. Improved knowledge regarding transplacental drug transfer and metabolism will result in further expansion of pharmacological treatment of fetal conditions.

Human uterine leukocytes and pregnancy

Abstract: In human pregnancy, the embryo implants into the specialized mucosal wall of the uterus (decidua) and the placenta starts to form. Cells from the placenta (trophoblasts) invade into the uterine mucosa in order to open up maternal uterine arteries to ensure an adequate supply of blood to the developing fetus. The trophoblasts have a unique immunological phenotype compared to most cells especially with regard to their expression of major histocompatibility complex (MHC) antigens. On the other side of the interaction, the uterine mucosa (endometrium) differentiates in preparation for implantation. One of the changes that takes place is the appearance in the endometrium of a large number of maternal leukocytes in the final part of the menstrual cycle. If pregnancy ensues, these leukocytes continue to increase in number and are found in close contact with trophoblasts. The composition of this population of maternal immune cells is unusual compared to that seen at other mucosal sites. A lot of research has focused on whether maternal T-cell responses are suppressed or modified during pregnancy. Research has also concentrated on the specialized uterine natural killer (NK) cells, which are found in the decidua in large numbers during early pregnancy. These uterine NK cells have been shown to express receptors for trophoblast MHC antigens, but their role in pregnancy is still mysterious. The purpose of this review is to give an overview of what is known about the immunology at the implantation site and also to provide an update of some of the most recent findings in this field.

Surfactant protein secreted by the maturing mouse fetal lung acts as a hormone that signals the initiation of parturition

Abstract: Parturition is timed to begin only after the developing embryo is sufficiently mature to survive outside the womb. It has been postulated that the signal for the initiation of parturition arises from the fetus although the nature and source of this signal remain obscure. Herein, we provide evidence that this signal originates from the maturing fetal lung. In the mouse, secretion of the major lung surfactant protein, surfactant protein A (SP-A), was first detected in amniotic fluid (AF) at 17 days postcoitum, rising progressively to term (19 days postcoitum). Expression of IL-1β in AF macrophages and activation of NF-κB in the maternal uterus increased with the gestational increase in SP-A. SP-A stimulated IL-1β and NF-κB expression in cultured AF macrophages. Studies using Rosa 26 Lac-Z (B6;129S-Gt(rosa)26Sor) (Lac-Z) mice revealed that fetal AF macrophages migrate to the uterus with the gestational increase in AF SP-A. Intraamniotic (i.a.) injection of SP-A caused preterm delivery of fetuses within 6-24 h. By contrast, injection of an SP-A antibody or NF-κB inhibitor into AF delayed labor by >24 h. We propose that augmented production of SP-A by the fetal lung near term causes activation and migration of fetal AF macrophages to the maternal uterus, where increased production of IL-1β activates NF-κB, leading to labor. We have revealed a response pathway that ties augmented surfactant production by the maturing fetal lung to the initiation of labor. We suggest that SP-A secreted by the fetal lung serves as a hormone of parturition.

Placental-specific insulin-like growth factor 2 (Igf2) regulates the diffusional exchange characteristics of the mouse placenta.

Abstract: Restricted fetal growth is associated with postnatal mortality and morbidity and may be directly related to alterations in the capacity of the placenta to supply nutrients. We proposed previously that imprinted genes can regulate nutrient supply by the placenta. Here, we tested the hypothesis that the insulin-like growth factor 2 gene (Igf2) transcribed from the placental-specific promoter (P0) regulates the development of the diffusional permeability properties of the mouse placenta. Using mice in which placental-specific Igf2 had been deleted (P0), we measured the transfer in vivo of three inert hydrophilic solutes of increasing size (14C-mannitol, 51CrEDTA, and 14C-inulin). At embryonic day 19, placental and fetal weights in P0 conceptuses were reduced to 66% and 76%, respectively, of wild type. In P0 mutants, the permeability.surface area product for the tracers at this stage of development was 68% of that of controls; this effect was independent of tracer size. Stereological analysis of histological sections revealed the surface area of the exchange barrier in the labyrinth of the mouse placenta to be reduced and thickness increased in P0 fetuses compared to wild type. As a result, the average theoretical diffusing capacity in P0 knockout placentas was dramatically reduced to 40% of that of wild-type placentas. These data show that placental Igf2 regulates the development of the diffusional exchange characteristics of the mouse placenta. This provides a mechanism for the role of imprinted genes in controlling placental nutrient supply and fetal growth. Altered placental Igf2 could be a cause of idiopathic intrauterine growth restriction in the human.

Fetal Programming: Prenatal Testosterone Excess Leads to Fetal Growth Retardation and Postnatal Catch-Up Growth in Sheep

Abstract: Alterations in the maternal endocrine, nutritional, and metabolic environment disrupt the developmental trajectory of the fetus, leading to adult diseases. Female offspring of rats, subhuman primates, and sheep treated prenatally with testosterone (T) develop reproductive/metabolic defects during adult life similar to those that occur after intrauterine growth retardation. In the present study we determined whether prenatal T treatment produces growth-retarded offspring. Cottonseed oil or T propionate (100 mg, im) was administered twice weekly to pregnant sheep between 30-90 d gestation (term = 147 d; cottonseed oil, n = 16; prenatal T, n = 32). Newborn weight and body dimensions were measured the day after birth, and postnatal weight gain was monitored for 4 months in all females and in a subset of males. Consistent with its action, prenatal T treatment produced females and males with greater anogenital distances relative to controls. Prenatal T treatment reduced body weights and heights of newborns from both sexes and chest circumference of females. Prenatally T-treated females, but not males, exhibited catch-up growth during 2-4 months of postnatal life. Plasma IGF-binding protein-1 and IGF-binding protein-2, but not IGF-I, levels of prenatally T-treated females were elevated in the first month of life, a period when the prenatally T-treated females were not exhibiting catch-up growth. This is suggestive of reduced IGF availability and potential contribution to growth retardation. These findings support the concept that fetal growth retardation and postnatal catch-up growth, early markers of future adult diseases, can also be programmed by prenatal exposure to excess sex steroids.

Autoantibodies against Folate Receptors in Women with a Pregnancy Complicated by a Neural-Tube Defect

Abstract: Background In the absence of clinical folate deficiency, periconceptional supplementation with folic acid reduces a woman's risk of having an infant with a neural-tube defect. Since antiserum to folate receptors induces embryo resorption and malformations in rats, we hypothesized that autoantibodies against folate receptors in women may be associated with pregnancy complicated by a neural-tube defect. Methods Serum from 12 women who were or had been pregnant with a fetus with a neural-tube defect and from 24 control women (20 with current or prior normal pregnancies and 4 who were nulligravid) was analyzed for autoantibodies by incubation with human placental folate receptors radiolabeled with [3H]folic acid. The properties of these autoantibodies were characterized by incubating serum and the autoantibodies isolated from serum with placental membranes, ED27 cells, and KB cells, which express the folate receptors. Results Serum from 9 of 12 women with a current or previous affected pregnancy (index subjec...

The fetal circulation

Abstract: Accumulating data on the human fetal circulation shows the similarity to the experimental animal physiology, but with important differences. The human fetus seems to circulate less blood through the placenta, shunt less through the ductus venosus and foramen ovale, but direct more blood through the lungs than the fetal sheep. However, there are substantial individual variations and the pattern changes with gestational age. The normalised umbilical blood flow decreases with gestational age, and, at 28 to 32 weeks, a new level of development seems to be reached. At this stage, the shunting through the ductus venosus and the foramen ovale reaches a minimum, and the flow through the lungs a maximum. The ductus venosus and foramen ovale are functionally closely related and represent an important distributional unit for the venous return. The left portal branch represents a venous watershed, and, similarly, the isthmus aorta an arterial watershed. Thus, the fetal central circulation is a very flexible and adaptive circulatory system. The responses to increased afterload, hypoxaemia and acidaemia in the human fetus are equivalent to those found in animal studies: increased ductus venosus and foramen ovale shunting, increased impedance in the lungs, reduced impedance in the brain, increasingly reversed flow in the aortic isthmus and a more prominent coronary blood flow.

Growth and compositional changes of fetal tissues in pigs

Abstract: Three hundred twenty fetuses were obtained from 33 pregnant gilts (Camborough-22, Pig Improvement Co.) to determine rates of nutrient deposition in fetal tissues and to estimate nutrient requirements for fetal growth. Pregnant gilts were fed an equal amount of a gestation diet (2.0 kg/d; as-fed basis), and were slaughtered at d 0, 45, 60, 75, 90, 102, or 110 of gestation (n = 3 to 6 per day). Fetuses were dissected into carcass and individual tissues (including gastrointestinal tract, liver, lung, heart, kidney, spleen [> or = d 75]), and partial placental collection was made for chemical analysis. Fetal tissues were weighed and analyzed for DM, ash, CP, and crude fat. Regression equations were obtained to explain the weight and compositional changes of individual tissues during gestation. Weights of the fetus, carcass, gastrointestinal tract, liver, heart, lung, and kidney increased cubically (P < 0.001), whereas brain weight increased linearly (P < 0.001) as gestation progressed. Fetal protein and fat contents increased quadratically (P < 0.001) as gestation progressed (R2 = 0.906 and 0.904, respectively). Changes in fetal protein and fat contents fit a multiphasic regression that consisted of two linear equations (P < 0.001, R2 = 0.988 and P < 0.001, R2 = 0.983, respectively), indicating that protein and fat growth accelerated after d 69 of gestation. Fetal protein and fat accretions were 0.25 and 0.06 g/d (P < 0.001) before d 69 of gestation, and increased to 4.63 and 1.09 g/d (P < 0.001) after d 69 of gestation. Protein needs for tissue protein gains increased 19-fold after d 69 of gestation. Results of this study indicate that the growth of the fetus and fetal tissues occurs at different rates during gestation and support the practice of a two-phase feeding strategy (before and after approximately d 70 of gestation) for pregnant gilts.

Effect of placental function on fatty acid requirements during pregnancy.

Abstract: The fetus has an absolute requirement for the n-3/n-6 fatty acids and docosahexaenoic acid (22:6 n-3; DHA) in particular is essential for the development of the brain and retina. Most of the fat deposition in the fetus occurs in the last 10 weeks of pregnancy. The likely rate of DHA utilisation during late pregnancy cannot be met from dietary sources alone in a significant proportion of mothers. De novo synthesis makes up some of the shortfall but the available evidence suggests that the maternal adipose tissue makes a significant contribution to placental transport to the fetus. The placenta plays a crucial role in mobilising the maternal adipose tissue and actively concentrating and channelling the important n-3/n-6 fatty acids to the fetus via multiple mechanisms including selective uptake by the syncytiotrophoblast, intracellular metabolic channelling, and selective export to the fetal circulation. These mechanisms protect the fetus against low long-chain polyunsaturated fatty acid (LCPUFA) intakes in the last trimester of pregnancy and have the effect of reducing the maternal dietary requirement for preformed DHA at this time. As a result of these adaptations, small changes in the composition of the habitual maternal diet before pregnancy are likely to be more effective in improving LCPUFA delivery to the fetus than large dietary changes in late pregnancy. There is little evidence that DHA intake/status in the second half of pregnancy affects visual and cognitive function in the offspring, but more studies are needed, particularly in children born to vegetarian and vegan and mothers who may have very low intakes of DHA.

A Longitudinal Study of Intrauterine Growth and the Placental Growth Hormone (GH)-Insulin-Like Growth Factor I Axis in Maternal Circulation: Association between Placental GH and Fetal Growth

Abstract: The aim of the study was 1) to evaluate the association of maternal serum levels of placental GH and IGF-I with fetal growth, and 2) to establish reference data for placental GH, IGF-I, and IGF-binding protein-3 (IGFBP-3) in normal pregnancies based on longitudinal measurements. A prospective longitudinal study of 89 normal pregnant women was conducted. The women had, on the average, seven blood samples taken and three ultrasound examinations performed. All had normal umbilical artery pulsatility indexes during pregnancy and gave birth to singletons between 37 and 42 wk gestation with birth weights above −2 sd. Placental GH levels were detectable in all samples from as early as 5 wk gestation and increased significantly throughout pregnancy to approximately 37 wk when peak levels of 22 ng/ml (range, 4.64–69.22 ng/ml) were reached. Subsequently, placental GH levels decreased until birth. The change in placental GH during 24.5–37.5 wk gestation was positively associated with fetal growth rate (P = 0.027) an...

Folic Acid Deficiency During Late Gestation Decreases Progenitor Cell Proliferation and Increases Apoptosis in Fetal Mouse Brain

Abstract: In mice and rats, maternal dietary choline intake during late pregnancy modulates mitosis and apoptosis in progenitor cells of the fetal hippocampus and septum. Because choline and folate are interrelated metabolically, we investigated the effects of maternal dietary folate availability on progenitor cells in fetal mouse telencephalon. Timed-pregnant mice were fed a folate-supplemented (FS), control (FCT) or folate-deficient (FD) AIN-76 diet from d 11-17 of pregnancy. FD decreased the number of progenitor cells undergoing cell replication in the ventricular zones of the developing mouse brain septum (46.6% of FCT), caudate putamen (43.5%), and neocortex (54.4%) as assessed using phosphorylated histone H3 (a specific marker of mitotic phase) and confirmed by bromodeoxyuridine (BrdU) labeling of the S phase. In addition, 106.2% more apoptotic cells were found in FD than in FCT fetal septum. We observed 46.8% more calretinin-positive cells in the medial septal-diagonal band region of FD compared with pups from control dams. FS mice did not differ significantly from FCT mice in any of these measures. These results suggest that progenitor cells in fetal forebrain are sensitive to maternal dietary folate during late gestation.

Fetal growth is directly related to maternal anthropometry and placental volume

Abstract: Objective: To describe the influence of maternal weight and weight gain, placental volume and the rate of placental growth in early pregnancy on fetal dimensions measured sonographically. Design: In a prospective study, 712 women were recruited from the antenatal clinic of the University Hospital of the West Indies. Data analysis was confined to 374 women on whom measurements of the placental volume at 14, 17 and 20 weeks gestation were complete. Measurements of maternal anthropometry and fetal size (by ultrasound) were performed. Weight gain in pregnancy between the first antenatal visit (8–10 weeks) and 20 weeks gestation, and the rate of growth of the placenta between 14–17 and 17–20 weeks gestation were calculated. Main outcome measures: Fetal anthropometry (abdominal and head circumferences, femoral length, and biparietal diameter) at 35 weeks gestation. Results: Lower maternal weight at the first antenatal visit was associated with a significantly smaller placental volume at 17 and 20 weeks gestation (P<0.002 and <0.0001 respectively). In all women, maternal weight gain was directly related to fetal anthropometry. Placental volume at 14 weeks gestation and the rate of growth of the placenta between 17 and 20 weeks gestation were significantly related to all four fetal measurements. Conclusion: This study has provided evidence that both placental volume, and the rate of placental growth may influence fetal size. These effects are evident in the first half of pregnancy, and appear to be mediated through maternal weight and weight gain. Sponsorship: This study was supported by a grant from the Wellcome Trust, 183 Euston Road, London, England.

Periconceptional Undernutrition in Sheep Accelerates Maturation of the Fetal Hypothalamic-Pituitary-Adrenal Axis in Late Gestation

Abstract: We investigated the effects of moderate maternal periconceptional undernutrition from 60 d before to 30 d after mating on fetal hypothalamic-pituitary-adrenal axis function in late gestation. Ewes were sampled regularly during the period of undernutrition for circulating hormone levels. Vascular catheters were inserted into ewes and their singleton fetuses at 112 d gestation (term, 145 d), and fetal ACTH(1-24) and metyrapone challenge tests were performed at 127 and 128 d. Postmortems were performed at 132 d. Fetuses of undernourished ewes (UN, n = 12) had elevated baseline cortisol concentrations (P < 0.05), compared with fetuses of ad libitum-fed ewes (n = 10). There were no differences between groups in fetal responses to ACTH challenge, but only UN fetuses demonstrated ACTH and 11-deoxycortisol responses to metyrapone (P < 0.05). UN fetuses had increased mRNA levels for proopiomelanocortin and prohormone convertase-1, but not -2, in the pars intermedia of the pituitary gland (P < 0.05). Glucocorticoid receptor mRNA levels were not different between groups in pituitary or hypothalamus. Maternal cortisol and ACTH levels during undernutrition were profoundly suppressed (P < 0.001), rather than elevated, in UN ewes. Furthermore, the normal pregnancy rise in maternal serum progesterone concentrations was delayed in undernourished mothers. These data demonstrate that events around the time of conception have profound effects on fetal hypothalamic-pituitary-adrenal development in late gestation and that factors other than fetal exposure to excess glucocorticoids may be important.

Nutritionally Mediated Placental Growth Restriction in the Growing Adolescent: Consequences for the Fetus

Abstract: Human adolescent pregnancy is characterized by poor pregnancy outcome; the risks of spontaneous miscarriage, prematurity, and low birth weight are particularly acute in girls who are still growing at the time of conception. Studies using a highly controlled sheep paradigm demonstrate that, in growing adolescents who are overnourished throughout pregnancy, growth of the placenta is impaired, resulting in a decrease in lamb birth weight relative to control-fed adolescents of equivalent age. Rapid maternal growth is also associated with increased spontaneous abortion rates in late gestation and a reduction in gestation length. Nutritionally sensitive hormones of the maternal somatotrophic axis may orchestrate nutrient partitioning in this paradigm and the particular role of growth hormone is discussed. At midgestation, the placentae of rapidly growing dams exhibit less proliferation in the fetal trophectoderm and reduced placental mRNA expression of a range of angiogenic factors. These changes occur before differences in placental size are apparent but may impact on subsequent vascularity. By late pregnancy, placental mass in the rapidly growing versus the control dams is reduced by approximately 45%; the fetuses display asymmetric growth restriction and are hypoxic and hypoglycemic. These growth-restricted pregnancies are associated with major reductions in absolute uterine and umbilical blood flows, leading to attenuated fetal oxygen, glucose, and amino acid uptakes. Placental glucose transport capacity is markedly reduced in the rapidly growing dams but is normal when expressed on a weight-specific placental basis. Thus, it is the small size of the placenta per se rather than alterations in its nutrient metabolism or transfer capacity that is the major limitation to fetal growth in the growing adolescent sheep. Information obtained from this highly controlled paradigm is clearly relevant to the clinical management of human adolescent pregnancies. In addition, the paradigm provides a robust model of placental growth restriction that replicates many of the key features of human intrauterine growth restriction per se.

Circulating cell‐free fetal DNA in maternal serum appears to originate from cyto‐ and syncytio‐trophoblastic cells. Case report

Abstract: Circulating cell-free fetal DNA in maternal serum offers an early and non-invasive method for prenatal diagnosis, but the origin of this DNA is still unknown. We report the absence of the SRY gene in maternal serum of a pregnant woman despite male genitalia at ultrasound. The karyotype was 45,X after direct trophoblast analysis and 45,X/46,Xidic(Yp) after culture and in all fetal tissues studied. Due to the absence of the SRY sequence in maternal blood and in the cytotrophoblast, we presume that free fetal DNA in this case originates from trophoblastic cells. As the case presented here is exceptional, it only has a minor impact on the accuracy of fetal sex determination by maternal serum analysis, but highlights the importance of and the necessity for the complementary ultrasonographic control.

Immunology of pregnancy. Implications for the mother.

Abstract: Pregnancy is a unique event in which a genetically and immunologically foreign fetus usually survives to full term without apparent rejection by the mother's immune system. Over the past decade, more information has been gathered to provide insight into the complex immunological mechanisms that allow the fetus to grow and survive in most cases. Whereas the maternal-fetal interface was once felt to be an immunologically privileged site with complete separation between the fetus and the mother, it is now known that recognition of the foreign fetus does occur. However, despite this immunological recognition, several mechanisms have been discovered which may explain why the mother does not reject the foreign fetus. These mechanisms include fetal factors such as trophoblast cell properties and altered MHC Class I expression as well as local maternal factors such as specialized uterine natural killer cells and a shifting of the T-helper cell cytokine profile from a type 1 to a type II array. Other novel immunomodulators are found to be expressed in the local uterine environment to aid in fetal survival. Furthermore, the persistence of fetal cells in the maternal circulation long after pregnancy is over (termed chronic microchimerism) and may have implications for autoimmune diseases. This review presents investigations and developments relevant to an understanding as to why the fetus is not rejected by the maternal immune system.