Elevations in the endogenous levels of the putative morphogen retinoic acid in embryonic mouse limb-buds associated with limb dysmorphogenesis

Retinoic acid, an endogenous metabolite of vitamin A (retinol), possesses striking biological activity akin to a morphogen in developing and regenerating vertebrate limbs. Systemic administration of retinoic acid (RA) to pregnant mammals during the period of limb organogenesis invariably results in dose-dependent dysmorphogenesis. In an attempt to uncover the mode of action of RA in the developing limb bud we analyzed, by HPLC methods, the levels of RA and its metabolic precursor, retinol, in embryonic mouse tissues prior to and following maternal exposure to a teratogenic dose of RA. Detectable levels of both RA and its isomer 13-cis-retinoic acid were found in the limb buds of Day 11 mouse embryos (40 +/- 2 somites). Although retinol was the major retinoid found in ethanolic extracts of either whole embryo or the limb buds, the latter is enriched in RA compared to the whole embryo. This indicated either a higher degree of retinol metabolism or a sequestration of RA in the limb bud compared to the rest of the embryo at this stage of development. A study of the time course of retinoid levels in treated embryos showed that changes occur rapidly, are stable for several hours, and then begin to return to pretreatment levels. After a maternal dose of 10 mg/kg RA, which resulted in a mild degree of limb anomalies, peak RA levels in the limb bud increased 50-fold over the endogenous level; a full 300-fold increase was found after a 100 mg/kg dose which results in 100% incidence of phocomelia. Interestingly, a dose-dependent depression in retinol levels was observed after RA treatment both in maternal plasma as well as the embryo. Studies are in progress to trace the intracellular disposition of both retinol and RA as well as any further active metabolite of RA in the limb buds and other embryonic tissues.     

Localization of artesunate and its derivatives in the pregnant rat and fetus following oral administration and relationship to developmental toxicity

BACKGROUND: The antimalarial drug artesunate affects erythroid cells leading to developmental toxicity and adult reticulocytopenia. We report on a kinetic study in rats and the tissue distribution of radioactivity following oral administration of [³H]‐artesunate to pregnant rats using quantitative whole‐body autoradiography (QWBA). METHODS: Rats were dosed orally with chlorproguanil/dapsone/artesunate (including 11.8 mg/kg artesunate) and plasma concentrations of artesunate and the active metabolite dihydroartemisinin (DHA) were determined. In the QWBA study, 6 rats received 13 mg/kg [³H]‐artesunate on day 18 of gestation. Groups of 2 rats were euthanized at 1, 6, and 24 hours after dosing, rapidly frozen, and sectioned in a cryostat. Sagittal sections were freeze‐dried and placed in contact with imaging plates. Tissue concentrations of radioactivity were quantified. RESULTS: Systemic exposure to DHA was up to 22‐fold higher than the parent compound and was higher in non‐pregnant females than males. In the QWBA study, high concentrations of radioactivity were seen in maternal tissues involved in absorption and excretion, the bone marrow and spleen. Fetal blood and liver levels were 3.8‐ to 8.8‐fold higher than maternal blood levels at all timepoints. CONCLUSIONS: Excluding tissues involved in absorption and excretion, the highest concentrations of radioactivity were observed in tissues involved in hemoglobin synthesis and/or destruction in both the mother and the fetus and likely account for the maternal reticulocytopenia and embryotoxicity. Radioactivity concentrations in the fetal blood were 2.1‐ to 2.8‐fold higher than maternal bone marrow at all timepoints and this difference could contribute to the lower dose threshold for embryotoxicity. Birth Defects Res (Part B) 89:364–375, 2010. © 2010 Wiley‐Liss, Inc.     

The fate of the hydrolysis products of thalidomide in the pregnant rabbit

1. The fate in the pregnant New Zealand White rabbit of oral doses of four ¹⁴C-labelled hydrolysis products of thalidomide, namely α-(o-carboxybenzamido)-glutarimide, 2-phthalimidoglutaramic acid, 2-phthalimidoglutaric acid and 2-(o-carboxybenzamido)glutaramic acid, administered on the 192nd hour of pregnancy has been studied. 2. About 60–95% of the administered ¹⁴C of each compound appears in the urine in 58hr. and the remainder is found in the faeces and in the gut and its contents. 3. Radioactivity is present in the plasma, liver, kidney, brain, muscle, fat and embryo. 4. The ¹⁴C-labelled substances in the plasma and embryo consist of the unchanged compounds and their further hydrolysis products. 5. Since the above four thalidomide hydrolysis products are found in the rabbit conceptus together with their further hydrolysis products after their oral administration to the pregnant rabbit, it appears that the teratogenic activity of thalidomide is due to the compound itself rather than to one or more of its hydrolysis products.     

Deposition of low dose benzo(a)pyrene into fetal tissue: influence of protein binding

The influence of maternal binding of benzo(a)pyrene (BaP) on its disposition into fetal tissue was investigated in pregnant Swiss-Webster mice. Low doses (10 ng/mouse) of radiolabeled BaP were administered by intravenous injection on day 15 of gestation. BaP was administered along with normal rabbit serum (NRS) (low binding paradigm) or anti-BaP antiserum (high binding paradigm) and animals killed at various time points. Total radioactivity in the fetus increased with time to peak concentrations in whole fetal homogenates at 12 hours. In contrast, maternal serum, liver, and lung showed a decrease in total radioactivity over the same time period. Total radioactivity/gram of fetal tissue was significantly higher in NRS-treated animals compared to anti-BaP-antiserum-treated animals. Since the levels of the parent compound, BaP, in fetal tissue fell over time similar to maternal liver and lung, the increase in total radioactivity in the fetus was due to an increased concentration of a BaP metabolite fraction in both the low binding and high binding groups. Significantly, a lower level of this metabolite fraction was found in fetal tissue from the anti-BaP-antiserum-treated animals. The present study shows that maternal exposure to this environmental pollutant, even at low doses, results in an accumulation of a metabolite-rich fraction in the fetal compartment, which may contribute to the teratogenic potential of BaP. The data also demonstrate that the amount of this accumulation can be diminished by increasing maternal binding proteins, such as by treatment with anti-BaP antiserum.     

Prostaglandin F and E levels in the conceptus, uterus and plasma during early pregnancy in the ewe

Concentrations of prostaglandins E and F (PGE and PGF) were measured in the embryo or fetus, extra embryonic or fetal membranes (membranes), intercaruncular and caruncular endometrium and plasma collected from uterine and ovarian arterial and venous vessels from separate groups of ewes laparotomized at 5 day intervals from day 10 to day 55 of pregnancy. Our purpose was to investigate the role of prostaglandins E and F in the maternal recognition of pregnancy, implantation and early placental function. Our data suggest that the initial maintenance of the corpus luteum in the pregnant ewe does not involve a reduction in PGF production, compared to pregnant ewes; but a change in the pattern of PGF secretion. This is accompanied by an elevation in PGE production of similar magnitude to that observed in non pregnant ewes. The extra embryonic/fetal membranes appear to be the major source of elevated PGF levels in the maternal circulation prior to day 30 of pregnancy. Between days 35 and 55 of gestation the rising PGF levels in maternal serum probably come from the fetus. Over the same period PGE levels rise in the fetus and intercaruncular endometrium, but PGE secretion into the maternal circulation is not enhanced. A role for PGF and PGE in fetal, placental and uterine growth is suggested; placental and uterine endocrine function may also be targets.     

Prostaglandin F and E levels in the conceptus, uterus and plasma during early pregnancy in the ewe

Concentrations of prostaglandins E and F (PGE and PGF) were measured in the embryo or fetus, extra embryonic or fetal membranes (membranes), intercaruncular and caruncular endometrium and plasma collected from uterine and ovarian arterial and venous vessels from separate groups of ewes laparotomized at 5 day intervals from day 10 to day 55 of pregnancy. Our purpose was to investigate the role of prostaglandins E and F in the maternal recognition of pregnancy, implantation and early placental function. Our data suggest that the initial maintenance of the corpus luteum in the pregnant ewe does not involve a reduction in PGF production, compared to pregnant ewes; but a change in the pattern of PGF secretion. This is accompanied by an elevation in PGE production of similar magnitude to that observed in non pregnant ewes. The extra embryonic/fetal membranes appear to be the major source of elevated PGF levels in the maternal circulation prior to day 30 of pregnancy. Between days 35 and 55 of gestation the rising PGF levels in maternal serum probably come from the fetus. Over the same period PGE levels rise in the fetus and intercaruncular endometrium, but PGE secretion into the maternal circulation is not enhanced. A role for PGF and PGE in fetal, placental and uterine growth is suggested; placental and uterine endocrine function may also be targets.     

Body fat in pregnant rats at mid- and late-gestation

Carcass fat content was estimated in fed 12- and 19-day pregnant rats and fed and 48 hour starved virgin females following both specific gravity determination and direct gravimetry of extracted lipids. No change in body fat accumulation was found in 12-day pregnant rats whereas in 19-day pregnant animals it increased significantly. A significant correlation was also found when the percentage of carcass fat was plotted against specific gravity considering values from all subjects. Results indicate that in spite of reported maternal anabolic changes in the rat at midgestation fat accumulation occurs later in pregnancy when the mother has the highest food intake, which makes available sufficient substrates to support both fetal growth and body lipidic deposition.     

PPAR-gamma,TNF-alpha messenger RNA levels and lipase activity in the pregnant and lactating rat

Dramatic alternations in maternal metabolism occur during gestation and lactation, especially glucose and fat metabolism. For example, in rats, the amount of body fat mass increases during gestation, then decreases just prior to delivery, and remains low after parturition. To investigate the factors involved in such changes in maternal fat mass, messenger ribonucleic acid (mRNA) levels of adipocytokines, peroxisome proliferator-activated receptor-gamma (PPAR-gamma) and tumor necrosis factor-alpha (TNF-alpha), were examined in the intraabdominal adipose tissue of non-pregnant rats, pregnant rats and postpartum rats. We also examined the issue of whether apoptosis, which could be promoted by PPAR-gamma and TNF-alpha, is involved in any of the changes in maternal fat mass The activity of lipoprotein lipase (LPL) and hormone sensitive lipase (HSL) in adipose tissue was also measured. PPAR-gamma and TNF-alpha mRNA levels remained constant during the gestational and postpartum periods. Apoptosis was not detected at any time as evidenced by DNA laddering and in situ staining. LPL activity was significantly increased at day 5 and remained elevated until day 14 of gestation. HSL activity was significantly increased at day 10 of gestation and then decreased after delivery, at day 10 of lactation. In conclusion, during the gestational and postpartum period of rats, changes in maternal fat mass did not directly correlate with the levels of expression of PPAR-gamma and TNF-alpha mRNA. Apoptosis also does not appear to influence on fat mass change. The changes in LPL and HSL activities during gestation suggest that these enzymes might be regulators of maternal adipose tissue level.     

Effects of retinoic acid and dimethylsulfoxide on the morphogenesis of the sea urchin embryo

Sea urchin embryos of the species Paracentrotus lividus were treated continuously with different concentrations of all-trans retinoic acid (RA) or dimethylsulfoxide (DMSO) at different developmental stages. A delay in embryonic development was observed when embryos were cultured in the presence of 2x10^?5 M RA, between 1 and 12 hours of development. Hence, at 48 hours of development, while control embryos had reached the pluteus stage, RA-treated embryos were at the prism stage. At 72 hours of development RA-treated embryos recovered and continued normal development reaching the pluteus stage. No effect was observed when treatment was performed before 1 hour or after 12 hours of developmet. DMSO treatment had no effect on normal sea urchin embryo development, although we observed that pigment cells, clearly visible at the pluteus stage, become visible earlier with respect to control embryos. This report confirms the advantages that the sea urchin embryo offers for the study of problems in cellular and developmental biology.     

Marked accumulation of valproic acid in embryonic neuroepithelium of the mouse during early organogenesis

Valproic acid, an antiepileptic drug, causes neural tube defects in mice and man. 14C-labeled valproic acid (sodium-salt) was administered to pregnant mice on days 8 and 9 of gestation (period of high sensitivity in regard to formation of neural tube defects in this species). Two dose levels of valproic acid (1 and 400 mg/kg) were used; in each case the total radioactivity administered was the same: 400 microCi/kg or 14.7 MBq/kg. Autoradiography combined with computerized densitometry revealed that in low-dose animals most of the radioactivity was confined to maternal liver and kidney, while at high doses more activity was observed in soft tissues and fluids, including amniotic fluid. In the embryo, the neuroepithelium showed the highest concentration, irrespective of dose and survival interval (30 min, 3 h, and 6 h). Upon administration of the high dose, up to five times more radioactivity (approximately 2,000 times more valproic acid) was recovered in embryonic tissues than after the low dose. It is concluded that high doses of VPA saturate the capacities of metabolism, excretion, and protein binding in the maternal organism, resulting in a higher proportion of the dose reaching the embryo, allowing more of the drug to be accumulated by the target organ, the neuroepithelium.     

Influence of acute heat stress on the development of GABAergic neurons in HPA-axies of mouse embryos

The damaging effects of acute heat stress in pregnant mice is well known, however, very little is known about the impact of heat on embryonic neurodevelopment and its dependence on the dam's physiological response to the stress. To study the changes in GABAergic neurons expression on the hypothalamo-pituitary-adrenocortical axis (HPA-axis), superoxide dismutase (SOD) activities and malondialdehyde (MDA) levels were measured in mouse embryos on E13-17 following acute, maternal heat stress. Blood samples and amniotic fluid from pregnant mice, and homogenates of whole embryos and embryo brains were collected for SOD and MDA analyses. SOD and MDA activities were measured in embryo and the sections by staining with anti-γ-aminobutyric acid-A- α1 receptor (GABAA receptor- α1), anti-γ-aminobutyric acid-B-1 receptor (GABAB receptor-R1) and anti-glutamate decarboxylase-65(GAD-65) antibodies. After the pregnant mice underwent acute heat stress on E13, the embryonic GABAergic neurons and GABA receptor expression were triggered immediately as a result of induction of the HPA-axis. This expression recovered to normal levels consistent with the control groups. However, the expression of the GABAA receptor in embryonic adrenal gland decreased continually. The SOD activity decreased in the embryonic brain and increased in the amniotic fluid after the heat stress, whereas the MDA levels increased in the maternal plasma only. Therefore, the GABAergic neurons in the developing HPA-axis of the embryos are susceptible to heat stress and the enhancement of SOD activities in the amniotic fluid might be a protective mechanism.     

Aminopeptidase N during the ontogeny of the chick

Little is known about the production and function of metallopeptidases in embryonic development. One such enzyme, aminopeptidase N (APN), is present in several epithelia, the brain and angiogenic vessels in adults. APN promotes vascular growth and endothelial cell proliferation in physiological and pathological models of angiogenesis. However, its possible role in embryonic angiogenesis or other developmental processes is unknown. Its expression profile in the early phase of embryonic development has not been reported. We report here the expression of this enzyme during the early development of the chick embryo, using complementary techniques for monitoring APN mRNA, protein, and enzymatic activity. We detected APN in the embryo as early as gastrulation. In addition to the known sites of APN production identified in both adults and rat fetuses toward the end of gestation, APN was found in unexpected sites, such as the primitive streak, the dorsal folds of the neural tube, the somites, and the primordia of several organs. APN was present mostly in the cardiovascular compartment during the first 13 days of incubation, and in the hematopoietic compartment (yolk sac and aorta-gonad-mesonephros region) early in development. This study provides clues as to the possible role of APN in embryonic development.     

Pharmacokinetic assessment of teratologically effective concentrations of an endogenous retinoic acid metabolite

Retinoic acid is a natural vitamin A derivative that undergoes oxidative metabolism in the body to yield several metabolites, which apparently represent the products of a detoxification pathway. To assess if such metabolic conversions diminished teratogenic potency, one of the major metabolites (4-oxo-all-trans-retinoic acid) was tested for its teratogenic activity in pregnant ICR mice and further investigated for its pharmacokinetic features to determine if it accumulated in the embryo in concentrations sufficient to elicit a teratogenic response. Administration of single oral doses (10, 25, 50, or 100 mg/kg) of the compound to ICR mice on day 11 of gestation (plug day = day 0) produced dose-dependent frequencies of serious fetal anomalies of the type usually associated with the use of retinoic acid and other retinoids. The metabolite was equivalent in teratogenic potency to retinoic acid, and, in the instance of cleft palate frequency, it was even more active. Concentrations of 4-oxo-all-trans-retinoic acid and its 13-cis isomer were measured in the maternal plasma and whole embryos at 30 min to 10 hr after administration of the lowest (10 mg/kg) and the highest (100 mg/kg) teratogenic dose of 4-oxo-all-trans-retinoic acid by means of high-performance liquid chromatography methodology. Distribution of the compound in the maternal system and transfer to the embryo occurred rapidly with either dose. Peak concentration in the maternal plasma and the embryo persisted for 3-4 hr after the higher dose but not with the lower dose; however, elimination kinetics for the two dose levels were similar.(ABSTRACT TRUNCATED AT 250 WORDS)     

禁食状态下MED1肝脏特异性敲除鼠呈现高脂血症

为研究MED1如何影响血浆脂质代谢,以MED1肝脏特异性敲除鼠 (MED1ΔLiv) 为动物模型,禁食0、24、48、72 h,通过H&E染色切片观察了MED1ΔLiv鼠肝脏的形态学变化,运用甘油三酯和胆固醇酶试剂盒及FPLC方法分析了MED1ΔLiv和对照鼠 (MED1fl/fl) 血浆甘油三酯和胆固醇的水平以及脂蛋白的分布情况。研究结果显示,禁食72 h,与MED1fl/fl和PPARα?/?对照鼠相比,MED1ΔLiv鼠肝脏无脂肪沉积。禁食24、48、72 h,与MED1fl/fl鼠相比,MED1Δ     

Transfer of cultured rabbit embryos

Embryo transfer experiments were carried out to study the developmental capacity of cultured rabbit embryos when transferred to recipients of variable postovulatory maturity. Rabbit embryos were flushed from the oviduct at 26 hours postcoitum (pc) and cultured in a modified Ham's F-10 medium supplemented with bovine serum albumin (BSA) for a period of 70 hours. At 96 hours pc the cultured embryos, which ranged from the early morula to the expanding blastocyst stage, were transferred to pseudopregnant recipients mated to vasectomized males 36 to 96 hours prior to the transfer procedure. Greatest embryo survival occurred when transfers were made to either the oviducts or uterine horns of recipients at 48 hours pc. Intermediate results for both implantation rates and number of young born were obtained with recipients at 36, 60, 72, and 84 hours pc. Transferred embryos consistently failed to survive the uterine environment of recipients 96 hours pc at transfer although this group was synchronous with embryonic chronological age. Oviductal transfers were generally more successful than uterine transfers. Markedly higher rates of embryo survival resulted from embryos that were collected 60 and 72 hours pc and transferred directly to synchronous recipients without an interim period of culture. Dissimilarity of development for in vivo grown rabbit embryos and those cultured in synthetic medium is demonstrated.     

Methylmercury distribution in the pregnant rat and embryo during early midbrain organogenesis

BACKGROUND: The period of neurogenesis represents a window of susceptibility for in utero methylmercury (MeHg) exposure. This study examined the toxicokinetics of potentially neurotoxic doses of MeHg during neurogenesis in the developing rat to provide additional information in the areas of mercury speciation and inter-study variability. METHODS: Pregnant Sprague-Dawley rats were dosed s.c. with 5-22 mg/kg MeHg on Day 11 of gestation to target rapidly dividing cells of the developing midbrain. Maternal liver, kidney, skin, blood, placenta, and the embryonic body and brain were evaluated for total and inorganic mercury content at 24, 48, and 72 hr after dosing. Tissue Hg partitioning ratios derived from our data were then compared to those derived from previous studies. RESULTS: Mercury was present in all tissues examined by 24 hr after dosing, and levels remained relatively stable over the subsequent 2 days in most tissues. The exceptions were the maternal blood and kidney, in which total mercury decreased significantly over the three days after dosing. Inorganic mercury concentrations were similarly stable over time. At maternal MeHg doses above 12 mg/kg, non-linearities were observed in mercury accumulation in the embryo, placenta and maternal liver. The mercury tissue partitioning coefficients ranged from 0.09 for maternal blood:embryo to 1.97 for maternal blood:kidney. CONCLUSIONS: Our observations at the 5 mg/kg dose were consistent with those of previous studies that involved evaluations at slightly later gestational times. The estimates of tissue partitioning coefficients we derived using multiple studies provide valuable insight into the effects of inter-study variability.     

The effect of starvation on tissue adenosine 3'-5' monophosphate levels

The effect of starvation on intracellular levels of 3′–5′, cAMP in liver, kidney, muscle, fat and isolated islets of Langerhans was studied. It was found that the concentration of cAMP increased in liver, kidney, muscle and fat, but decreased in the islets after 48–72 hours of starvation. Similar studies were conducted on liver, kidney, muscle and fat of hypophysectomized rats and identical results were obtained.     

Zinc-α2-Glycoprotein Is Unrelated to Gestational Diabetes: Anthropometric and Metabolic Determinants in Pregnant Women and Their Offspring

Context

Zinc-α2-Glycoprotein (ZAG) is an adipokine with lipolytic action and is positively associated with adiponectin in adipose tissue. We hypothesize that ZAG may be related with hydrocarbonate metabolism disturbances observed in gestational diabetes mellitus (GDM).

Objective

The aim of this study was to analyze serum ZAG concentration and its relationship with carbohydrate metabolism in pregnant women and its influence on fetal growth.

Design

207 pregnant women (130 with normal glucose tolerance (NGT) and 77 with GDM) recruited in the early third trimester and their offspring were studied. Cord blood was obtained at delivery and neonatal anthropometry was assessed in the first 48 hours. ZAG was determined in maternal serum and cord blood.

Results

ZAG concentration was lower in cord blood than in maternal serum, but similar concentration was observed in NGT and GDM pregnant women. Also similar levels were found between offspring of NGT and GDM women. In the bivariate analysis, maternal ZAG (mZAG) was positively correlated with adiponectin and HDL cholesterol, and negatively correlated with insulin and triglyceride concentrations, and HOMA index. On the other hand, cord blood ZAG (cbZAG) was positively correlated with fat-free mass, birth weight and gestational age at delivery. After adjusting for confounding variables, gestational age at delivery and HDL cholesterol emerged as the sole determinants of cord blood ZAG and maternal ZAG concentrations, respectively.

Conclusion

mZAG was not associated with glucose metabolism during pregnancy. ZAG concentration was lower in cord blood compared with maternal serum. cbZAG was independently correlated with gestational age at delivery, suggesting a role during the accelerated fetal growth during latter pregnancy.     

东太平洋浅海长尾鲨母体和胚胎间痕量元素的迁移规律

大洋中上层鲨鱼多为金枪鱼渔业的兼捕渔获,因其生长缓慢、繁殖力低等生活史特征,极易被过度捕捞,90%种类资源已近危。而作为长生命周期的顶级捕食者,鲨鱼体内某些过高的痕量元素含量不利于资源恢复。本研究选取10尾东太平洋雌性浅海长尾鲨(Alopias pelagicus)及对应的18尾胚胎,测定其肌肉和肝脏中锌(Zn)、铜(Cu)、铬(Cr)、镍(Ni)、锰(Mn)、硒(Se)、钴(Co)、汞(Hg)、镉(Cd)、铅(Pb)和砷(As) 11种痕量元素,探寻浅海长尾鲨繁殖过程中母体与胚胎间痕量元素的迁移规律。结果表明: 对于必需元素,胚胎两种组织的Cr、Cu、Se和Mn含量均高于母体对应组织,而Ni和Zn含量在胚胎肌肉中较高、肝脏中较低;对于非必需元素,胚胎两种组织的As、Cd和Hg含量均低于母体对应组织。虽然Hg在母体和胚胎组织中含量均较高,但胚胎组织的Se/Hg均大于1,且其在胚胎中的值均大于母体,表明Se在胚胎中具有显著抑制Hg毒性的作用。肝脏作为鲨鱼胚胎发育的主要能量来源,其元素含量在胚胎与母体之间无显著相关性。由此推测,浅海长尾鲨可能存在特定的元素调控机制,以维持胚胎组织中元素含量的稳定。     

Fetal monkey absorption of 55Fe from amniotic fluid.

A single dose of 0.5 mCi radioiron (55Fe) was injected directly into the amniotic cavity of each of four pregnant monkeys near term. At 6 or 24 hours after 55Fe adminstration, samples of fetal jejunum, ileum, blood, spleen, liver, lung and fetal membranes were taken for radioautography and scintillation counts. Counts were also made on corresponding maternal tissues. Intestinal radioiron levels and localization indicated that fetuses swallowed and absorbed 55Fe within 6 to 24 hours after injection. Silver grains over the meconium bodies of fetal ileum suggested that intestinal epithelium retained at least some of the absorbed radioiron. However, elevated 55Fe levels in fetal blood and hematopoietic organs indicated that transport of radioiron to the circulation had occurred, presumably through fetal intestine, extraembryonic membranes and/or fetal lungs. Transfer of 55Fe across the placenta from fetus to mother occurred at a slow rate, i.e., samples of maternal organs obtained at 24 hours gave low counts.