Showing papers on "Fetus published in 1988"

Expression of Somatomedin/Insulin-Like Growth Factor Messenger Ribonucleic Acids in the Human Fetus: Identification, Characterization, and Tissue Distribution*

Abstract: Several lines of evidence indicate that multiple human fetal tissues synthesize somatomedins/insulin-like growth factors (Sm/IGFs). To investigate the synthesis of Sm/IGFs in vivo, we isolated polyadenylated RNAs from multiple human fetal tissues of 16–20 weeks gestation and performed Northern and dot-blot analyses using 32P-labeled cDNAs and oligodeoxyribonucleotide (oligomer) probes complementary to human Sm-C/IGF-I and IGF-II mRNAs. Sm-C/IGF-I mRNAs were present in all tissues studied. IGF-II mRNAs were detectable in all tissues except the cerebral cortex and hypothalamus. IGF-II mRNA levels were consistently higher than Sm-C/IGF-I mRNAs in all tissues where IGF-II mRNAs were detectable (varying from 2-fold higher in spleen and thymus to 650-fold higher in liver), suggesting that IGF-II is synthesized in greater quantities than Sm-C/IGF-I in most tissues during early fetal life. Liver, adrenal, and skeletal muscle had the highest levels of IGF-II mRNAs, while placenta and stomach had the highest level ...

Evidence for a novel parathyroid hormone-related protein in fetal lamb parathyroid glands and sheep placenta: comparisons with a similar protein implicated in humoral hypercalcaemia of malignancy

Abstract: Parathyroid hormone (PTH)-like bioactivity, assayed as adenylate cyclase response in UMR 106-01 osteogenic sarcoma cells, was present in extracts of sheep fetal and maternal parathyroid glands and placenta. Preincubation of extracts with PTH(1-34) antiserum inhibited approximately 40% of the bioactivity in fetal parathyroid extracts, 50% in maternal parathyroid extracts, but only 10% of the bioactivity in the placental extract. Partial purification of placental extracts by chromatography yielded fractions containing PTH-like bioactivity which were similar in behaviour to that of PTH-related protein (PTHrP) from a human lung cancer cell line (BEN). An antiserum against synthetic PTHrP(1-16) partially inhibited the bioactivity of the placental extract and synthetic PTHrP(1-34), but had no effect on the bioactivity of bovine PTH(1-34) or bovine PTH(1-84). The placental PTH-like bioactivity was higher in mid- than in late gestation. Fetal parathyroid glands contained the highest PTH-like bioactivity. Thyroparathyroidectomy of one fetal twin lamb in each of 16 ewes between 110 and 125 days of gestation resulted in decreases of the plasma calcium concentration and reversal of the placental calcium gradient that existed between the ewe and the intact fetus. Perfusion of the placenta of each twin in anaesthetized ewes was carried out sequentially with autologous fetal blood in the absence of the exsanguinated fetus. The plasma calcium concentration in the blood perfusing the placenta of each twin increased, but reached a plateau at a lower concentration in the perfusing blood of thyroparathyroidectomized fetuses than in that of the intact fetuses. Addition of extracts of fetal parathyroid glands or of partially purified PTHrP resulted in further increases in plasma calcium in the autologous blood perfusing the placentae of thyroparathyroidectomized fetuses, but addition of bovine PTH(1-84) or rat PTH(1-34) had no effect. The presence of this PTH-like protein in the fetal parathyroid gland and placenta may contribute to the relative hypercalcaemia of the fetal lamb. This protein, which is similar to PTHrP associated with humoral hypercalcaemia of malignancy, stimulates the placental calcium pump responsible for maintaining a relative fetal hypercalcaemia during gestation.

Developmental expression of transforming growth factors alpha and beta in mouse fetus.

Abstract: Expression of mRNA for transforming growth factor alpha (TGF-alpha) and TGF-beta 1 during the fetal development of mice was evaluated by in situ hybridization. TGF-alpha mRNA was detected in 9- and 10-day fetuses but was absent in older fetuses. TGF-alpha mRNA-containing cells were found in the placenta, otic vesicle, oral cavity, pharyngeal pouch, first and second branchial arches, and developing kidneys. mRNA for TGF-beta 1 was present in hematopoietic cells of blood islands and capillaries and in the liver as it began to bud off on day 10 and function as a hematopoietic organ.

The fate of fetal Leydig cells during the development of the fetal and postnatal rat testis

Abstract: The ultrastructure and developmental fate of the fetal generation of Leydig cells of the rat testis was studied from the 17th day of fetal life up to 100 days after birth. The number of fetal Leydig cells per testis was determined by light microscopic morphometric analysis of semithin plastic sections. In fetal testes (days 17-22 postconception), Leydig cells exhibited a characteristic ultrastructure, containing smooth endoplasmic reticulum, many lipid inclusions and glycogen. Testes of 17-day-old fetuses contained about 25 x 10(3) fetal Leydig cells, rapidly increasing to 90 x 10(3) per testis in 21-day-old fetuses. After birth, fetal Leydig cells per testis remained relatively constant up to 2 weeks (80-90 x 10(3) per testis) and were identified by light and electron microscopy which showed their numerous lipid inclusions, their tendency for clustering and their association with interstitial tissue fibroblasts which partly encapsulated the fetal Leydig cells. From 21-100 days after birth, fetal Leydig cell numbers were quite variable with a mean of 45-60 x 10(3) per testis. These results are the first to show that the fetal generation of Leydig cells persist in the adult testis and do not undergo early postnatal degeneration or dedifferentiation into other interstitial cells. The simultaneous occurrence of the fetal Leydig cells and the adult population of Leydig cells indicates that these cells are distinct cell generations which are developmentally unrelated.

Plasma cortisol and adrenocorticotropin in appropriate and small for gestational age fetuses.

Abstract: Plasma cortisol and adrenocorticotropin (ACTH) were measured in fetal blood samples obtained by cordocentesis from 61 appropriate for gestational age (AGA) and in 41 small for gestational age (SGA) fe

Erythropoietin messenger RNA levels in developing mice and transfer of 125I-erythropoietin by the placenta.

Abstract: Erythropoietin (EP) mRNA was measured in normal and anemic mice during fetal and postnatal development. Normal fetal livers at 14 d of gestation contained a low level of EP mRNA. By day 19 of gestation, no EP mRNA was detected in normal or anemic fetal livers or normal fetal kidneys, but anemic fetal kidneys had low levels of EP mRNA. Newborn through adult stage mice responded to anemia by accumulating renal and hepatic EP mRNA. However, total liver EP mRNA was considerably less than that of the kidneys. Juvenile animals, 1-4 wk old, were hyperresponsive to anemia in that they produced more EP mRNA than adults. Moreover, nonanemic juveniles had readily measured renal EP mRNA, whereas the adult level was at the lower limit of detection. Because of the very low level of fetal EP mRNA, placental transfer of EP was evaluated. When administered to the pregnant mouse, 125I-EP was transferred in significant amounts to the fetuses. These results indicate that in mice the kidney is the main organ of EP production at all stages of postnatal development and that adult kidney may also play some role in providing EP for fetal erythropoiesis via placental transfer of maternal hormone.

Developmental changes in rat brain 5'-deiodinase and thyroid hormones during the fetal period: the effects of fetal hypothyroidism and maternal thyroid hormones.

Abstract: We have studied the ontogenesis of 5'-deiodinase (5'D) activity in rat brain during fetal life, its capacity to respond to maternal or fetal hypothyroidism, and its regulation by maternal thyroid hormones. Type II 5'D (5' D-II) activity increases 4-fold during the period studied (17 to 22 days of gestation), mainly between days 19 and 21. Fetal brain T4 concentrations increase in parallel with fetal plasma T4, whereas fetal brain T3 concentrations increase 18 times (days 17-21), six times more than would have been expected from the small increase in fetal plasma T3 levels. Maternal thyroidectomy did not affect 5'D-II activity or thyroid hormone concentrations in fetal brain (except brain T4 at 18 days of gestation). Fetal hypothyroidism, induced by giving a goitrogen (methimazole) to the mothers, depleted all fetal tissues studied, including the fetal thyroid, from thyroid hormones. By 19 days of gestation, the fetal brain was able to respond to hypothyroidism with a 3- to 5-fold increase in 5'D-II activity. Earlier onset of treatment with methimazole led to 2- to 3-fold increases in 5'D already at 17 and 18 days of gestation, showing that when fetal thyroid secretion starts the fetal brain 5'D-II is able to respond to hypothyroidism. Replacement of methimazole-treated mothers with physiological doses of T4, given by constant infusion, increased T4 and T3 concentrations in fetal brain, and inhibited fetal, as well as maternal, brain 5'D-II activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Butyrate infusions in the ovine fetus delay the biologic clock for globin gene switching.

Abstract: The switch from fetal to adult hemoglobin expression is regulated in many mammalian species by a developmental clock-like mechanism and determined by the gestational age of the fetus Prolonging fetal globin gene expression is of considerable interest for therapeutic potential in diseases caused by abnormal beta-globin genes Butyric acid, which is found in increased plasma concentrations in infants of diabetic mothers who have delayed globin gene switching, was infused into catheterized fetal lambs in utero during the time of the normal globin gene switch period The globin gene switch was significantly delayed in three of four butyrate-treated fetuses compared with controls and was entirely prevented in one fetus in whom the infusion was begun before the globin switch was under way These data provide a model for investigating and arresting the biologic clock of hemoglobin switching

Development of pulmonary vascular response to oxygen

Abstract: The ability of the pulmonary circulation of the fetal lamb to respond to a rise in oxygen tension was studied from 94 to 146 days of gestation. The unanesthetized ewe breathed room air at normal atmospheric pressure, followed by 100% oxygen at three atmospheres absolute pressure in a hyperbaric chamber. In eleven near-term lambs (132 to 146 days of gestation), fetal arterial oxygen tension (PaO2) increased from 25 +/- 1 to 55 +/- 6 Torr (mean +/- SE), which increased the proportion of right ventricular output distributed to the fetal lungs from 8 +/- 1 to 59 +/- 5%. In five very immature lambs (94 to 101 days of gestation), fetal PaO2 increased from 27 +/- 1 to 174 +/- 70 Torr, but the proportion of right ventricular output distributed to the lung did not change, 8 +/- 1 to 9 +/- 1%. In five of the near-term lambs, pulmonary blood flow was measured. It increased from 34 +/- 3 to 298 +/- 35 ml.kg fetal wt-1.min-1, an 8.8-fold increase. We conclude that the pulmonary circulation of the fetal lamb does not respond to an increase in oxygen tension before 101 days of gestation; however, near term an increase in oxygen tension alone can induce the entire increase in pulmonary blood flow that normally occurs after the onset of breathing at birth.

Sterol synthesis and low density lipoprotein clearance in vivo in the pregnant rat, placenta, and fetus. Sources for tissue cholesterol during fetal development.

Abstract: Whereas the greatest relative increase in body mass occurs during the third trimester of fetal life, the source of the cholesterol that supports this growth is uncertain. These studies used [3H]water and 125I-cellobiose-labeled low density lipoproteins to quantitate absolute rates of cholesterol acquisition in vivo by the fetus of the rat. Preliminary studies demonstrated that [3H]water administered intravenously to the mother rapidly equilibrated with the body pool of water in the fetus and that 22-microgram atoms of H from the water pool were incorporated into each micromole of newly synthesized cholesterol. After administration of [3H]water to pregnant rats, the rates of sterol synthesis per 100 g of whole body weight were severalfold higher in the fetus than in the dams. Individual organs of the dam such as the liver, however, had much higher synthetic rates than those in the fetus. When maternal hepatic cholesterol synthesis was suppressed by cholesterol feeding, newly synthesized cholesterol disappeared from the maternal blood yet there was essentially no change in the rate of appearance of newly synthesized sterol in the fetus, placenta, and fetal membranes. The placenta did take up low density lipoproteins at rates equal to about one-third of that seen in the maternal liver, but none of the apolipoprotein or cholesterol was transferred to the fetus. These studies indicate that the rat fetus receives little or no cholesterol from the mother but, rather, satisfies its need for cholesterol during fetal development through local synthesis. Furthermore, the fetal membranes appear to be an important site for sterol synthesis in the fetal compartment.

Immunohistochemistry of Carcino-Embryonic Antigen in the Embryo, Fetus and Adult

Abstract: This study concerns the immunohistologic distribution of carcino-embryonic antigen (CEA) in tissues and organs from 86 legal abortions, stillborn fetuses and perinatal deaths and from 5 adults without

Essentials of human embryology

Abstract: GAMETOGENESIS, FERTILIZATION, And the FIRST WEEK: Origin of the Germ Line, Meiosis, Gametogenesisin the Male and Female, the Menstrual Cycle, Fertilization, Cleavage the SECOND WEEK: Development of the Bilaminar Germ Disc and Establishment of the Uteroplacental Circulation the THIRD WEEK: Gastrulation, Formation of the Trilaminar Germ Disc, And Initial Development of the Somites and Neural Tube the FOURTH WEEK: Differentiation of the Somites and the Nervous System, Segmental Development and Integration DEVELOPMENT of the PERIPHERAL NERVOUS SYSTEM: Integration of the Developing Nervous System, Innervation of Motor and Sensory End Organs EMBRYONIC FOLDING: Folding of the Embryo and Formation of the Body Cavities and Mesenteries: Development of the Lungs DEVELOPMENT of the HEART: Formation and Folding of the Primitive Heart Tube: Morphogenesis of the Heart Chambers and Valves, Development of the Cardiac Conduction System DEVELOPMENT of the VASCULATURE: Vasculogenesis, Development of the Aortic Arches and Great Arteries, Development of the Vitelline, Umbilical, And Cardinal Venous Systems, Development of the Coronary Circulation, Circulatory Changes at Birth DEVELOPMENT of the GASTROINTESTINAL TRACT: Development of the Stomach, Liver, Digestive Glands, And Spleen, Organization of the Mesenteries, Folding and Rotation of the Midgut, Septation of the Cloaca and Formation of the Anus DEVELOPMENT of the UROGENITAL SYSTEM: Development of the Cervical Nepphrotomes, Mesonephric and Metanephric Kidneys, And Urogenital Duct Systems, Development of the Gonads and Genitalia DEVELOPMENT of the LIMBS: Development of the Limb Buds, Functions of the Apical Ectodermal Ridges and Mesodermal Core, Formation of the Hand and Foot Plates, Development of the Appendicular Skeleton and Musculature DEVELOPMENT of the HEAD, The NECK and the EYES and EARS DEVELOPMENT of the BRAIN and CRANIAL NERVES: Development of the Subdivisions of the Brain, Organization O F the Cranial Nerves and Their Nuclei and Ganglia, Cytodifferentiation in the Brain, Development of the Ventricular System DEVELOPMENT of the INTEGUMENTARY SYSTEM: Development of the Skin, Hair, Epidermal Glands, Nails, And Teeth FETAL DEVELOPMENT and the FETUS as PATIENT: the Fetal Period, Development and Functioning of the Placenta, Teratogenesis and Fetal Infections, Fetal Diagnosis, Fetal Surgery, And Gene Therapy

Cyclosporine and its metabolites in mother and baby.

Abstract: Cyclosporine (CsA) is a potent immunosuppressive agent that has significantly improved allograft survival in recipients of human organ transplants (1, 2). Recently there have been a few cases of successful pregnancies in transplant patients receiving CsA alone or in combination with steroids (3, 4). A general concern regarding pregnancy in transplant patients is the potential harmful effect of chronic maternal immunosuppression on the fetus. It is essential to determine the extent of exposure of the fetus to the immunosuppressive drug and its metabolites. We recently studied the concentrations of CsA and several of its metabolites in maternal and cord blood, placenta, and the umbilical cord in two patients receiving chronic CsA therapy. The first patient was a 26-year-old woman with primary biliary cirrhosis secondary to common bile duct obstruction who received a successful liver transplantation in November 1985. Immunosuppression was achieved with CsA and steroids. During the second postoperative week she also received the monoclonal antibody OKT 3. In February 1987, she delivered a 3208 g baby boy. At the time of delivery she was receiving CsA 200 mg orally b.i.d., prednisone 10 mg, hydralazine 50 mg q.i.d., ferrous sulphate 300 t.i.d, furosemide 40 mg q.d. and multivitamin therapy. On the day of the delivery she received CsA at 10 A.M. and the baby was born at 5:45 P.M. Maternal blood was obtained at 8.5 hr after CsA administration while cord blood was obtained at 7.8 hr after CsA administration. Maternal and cord blood along with placenta and umbilical cord were analyzed for CsA and several of its metabolites using a gradient high-pressure liquid chromatographic method developed in our laboratory (5). The second patient was a 25-year-old woman who received an orthotopic liver transplant in November 1985 for cirrhosis of unknown cause. Immunosuppression was achieved with CsA and steroids. Four weeks following the transplant, the patient developed cytomegalovirus hepatitis from which she recovered with reduction in immunosuppression. She did well for 10 months and then developed biliary obstruction that was corrected surgically. At this time she became pregnant. Pregnancy was complicated by anemia requiring blood transfusions and preeclampsia. At gestational age 36 weeks, she had a caesarean section because of fetal distress, and a live baby boy (weight 1690 g) was delivered at 8 A.M. At the time of delivery her medications included Riopan 30 ml p.o. every 4 hr, ranitidine 150 mg orally b.i.d., ferrous sulfate 300 mg orally t.i.d., prednisone 15 mg orally every day and CsA 125 mg orally every 12 hr. Maternal and fetal cord blood were drawn simultaneously at the time of delivery 10 hr after the previous oral cyclosporine dose. The baby had intrauterine growth retardation, as the weight and head circumference were below the fifth percentile. The blood samples, umbilical cord, and placenta were refrigerated at 4°C until analyzed by HPLC. Table 1 lists the concentrations of CsA and its metabolites in blood and in different tissues. The highest concentration of CsA was seen in the umbilical cord of patient 1. The placenta contained CsA concentrations nearly five to ten times greater thon the maternal and the fetal blood, and had the highest concentrations of all the metabolites measured. While small concentrations of M 21 were observed in the placenta and the maternal blood of patient 1, M 18 concentrations were below measurable levels in most of the specimens. Table 1 Cyclosporine and its metabolites in mother and childa Cyclosporine is very lipid-soluble, extensively distributed in the body, and highly metabolized. Previous studies have reported the presence of CsA in cord blood, placenta, amniotic fluid, and breast milk (4). In addition to CsA, we have observed high concentrations of CsA metabolites in the placenta, indicating the presence of CsA metabolizing enzymes in this tissue and/or accumulation of these metabolites in the placenta. Very high concentrations of CsA (nearly 30 times that of the maternal blood) were also observed in the umbilical cord of one patient. Some of the metabolites, particularly M 17, appear in very high concentrations in the blood and also possess significant immunosuppressive effect (6, 7). Whether the metabolites of CsA also contribute to the toxicity is not known. In this study we report for the first time the concentrations of CsA metabolites in cord blood, placenta, and umbilical cord. Of interest is the relatively high concentration of all the metabolites in the placenta. While no specific harmful effects attributable to CsA were observed in the baby, it is clear that the fetus is exposed not only to CsA but also to its metabolites. According to the tests conducted by Sandoz Inc. (Basel, Switzerland) CsA is not mutagenic in the Ames test and did not produce any chromosomal abnormalities in animals. However, since the fetus is exposed to chronic CsA and its metabolites, the immediate septic complications and the possible long-term effects on gestationally immunosuppressed children should be investigated.

Transfer of thyroxine from the mother to the rat fetus near term: effects on brain 3,5,3'-triiodothyronine deficiency.

Abstract: It has recently been shown that thyroid hormones are transferred from the mother to the developing rat embryo early in gestation, before the onset of fetal thyroid function We have now studied whether there is transfer of T4 from the mother to the fetus late in gestation when the fetal thyroid is impaired Normal and thyroidectomized females were mated, given a goitrogen [methimazole (MMI)], starting before the onset of fetal thyroid function and until term, alone or together with a constant infusion of T4 (18 micrograms/100 g BWday) T4 and T3 were determined by RIA in several maternal samples and in tissues from 21-day-old fetuses The administration of MMI blocked the fetal thyroid, as assessed from the decreased thyroid concentrations of T4 and T3 The concentrations of both iodothyronines also decreased in placenta, thyroid, plasma, brain, liver, lung, and carcass of fetuses from MMI-treated dams Infusion of T4 into such MMI-treated mothers partly avoided this decrease, and T4 levels increased in all fetal tissues to 41-57% of those in normal fetuses In contrast to this, T4 infusion affected the concentration of T3 to varying degrees in different tissues The T3 concentration in plasma and lung increased very little when the MMI-treated mother was infused with T4, but in the brain T3 reached concentrations comparable to those in normal fetuses Results not only show transfer of T4 from the mother to the fetus near term, at least when the fetal thyroid is impaired, but also suggest that it might mitigate, or avoid, the adverse effects of such failure on the developing brain

Vitamin D supply to the rat fetus and neonate.

Abstract: The prevention of neonatal rickets by oral supplementation with vitamin D2 (ergocalciferol) has tended to obscure our ignorance of the natural mechanism by which young mammals receive an adequate supply of vitamin D. To investigate the possibility of specific intrauterine transfer and storage of vitamin D in fetal tissues, vitamin D-deficient female rats were given depot injections of 3H- or 14C-labeled vitamin D3 (cholecalciferol) before mating and the 3H-labeled animals were killed at stages during the last third of gestation. Analysis of lipid extracts from whole fetuses revealed a linear increase in the concentration of 25-hydroxyvitamin D3, 24,25-dihydroxyvitamin D3, and D3 itself between days 14 and 19 of gestation. During this period the elimination half-time of 3H-labeled molecules in maternal plasma fell from 27.1 to 4.4 d, suggesting that a specific mechanism was transferring vitamin D molecules into the fetuses. The vitamin was stored predominantly as 25-hydroxyvitamin D3 and 24,25-dihydroxyvitamin D3, with the highest concentrations in fetal muscle. Immediately after birth, pups from 3H- and 14C-labeled mothers were exchanged and later killed after 1-3 wk of suckling. Analysis of total lipid extracts for 3H and 14C content determined the relative contributions of vitamin D supplied before birth via the placenta and after birth in the maternal milk. The vitamin D content of the rat milk was relatively high, between 1.0 and 3.5 micrograms/liter. Nevertheless, the supply of vitamin D in utero, rather than from milk, was the main determinant of vitamin D status in early neonatal life. This is the first indication in a mammal of a specific transfer mechanism that allows the fetus to accumulate vitamin D from the mother during the last third of gestation.

Effects of maternal stress during different gestational periods on the serotonergic system in adult rat offspring.

Abstract: Pregnant Sprague-Dawley rats were exposed to mild stress treatments during different gestational periods and the offspring were investigated at 60 days of age. In the first study, stress from embryonic day (ED) 11 to ED 20 produced effects similar to those reported following stress throughout pregnancy; increased numbers of 5-HT 2 binding sites in cerebral cortex and a reduced intensity of the behavioral syndrome produced by injections of the 5-HT agonist 5-methoxy-N, N-dimethyltryptamine (5-MeODMT). In the second study, stress from ED 3 to ED 14 had no significant effect on the intensity of the 5-MeODMT-elicited 5-HT syndrome while stress from ED 15 to ED 20 had a similar effect as stress throughout pregnancy. These data provide evidence that the critical period for prenatal stress-induced changes in brain 5-HT neurons is between ED 15 and birth. This suggests that the mechanism involves an interaction with developmental events occuring within this time span such as the growth of nerve axons and the formation of synaptic contacts. Our findings also provide further evidence that stress during the final trimester of pregnancy may have serious adverse effects on fetal brain development.

The epidemiology of repeated abortion

Abstract: It is generally accepted that about 15% of all recognised pregnancies are miscarried, or aborted before the 28th week, most before the 12th week, and if we were able to measure embryonic death rates immediately after fertilisation this proportion would be considerably higher. There is a large number of causes for such losses, including anomalies of the embryonic or fetal karyotype; major fetal malformations; fetal infections; the presence of chronic maternal illness; maternal uterine anomalies and hormonal or immunological problems.