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Applications of minisatellite variant repeat (MVR) mapping for maternal identification from remains of an infant and placenta.

Minisatellite variant repeat (MVR) mapping using the polymerase chain reaction (PCR) at D1S8 (MS32) was applied to a practical forensic case of an infant and placenta found in an incinerator. They were thought to be left for a few days postmortem, and the infant was severely burnt when found. DNA was extracted from the infantile muscle and maternal placental hematoma. MVR-PCR analysis as well as other common DNA typing (D1S80, HLA-DQA1) were performed on both DNA samples. Both MVR diploid codes were matched although some extra faint bands in the ladder were observed from the maternal placental sample, which probably indicated superimposing of an allele derived only from the mother, and not the infant. In order to detect the original maternal alleles, three flanking polymorphic sites were typed and allele-specific MVR-PCR was performed. Finally, one maternal allele not inherited by the infant and two alleles from the infant were typed. Two alleles suggested the infant and/or mother was Japanese. The two diploid codes including one possibly from the mother were deduced and compared with other codes in the databases for evaluating the discriminating power.

Base Sequence↗

Determinants of polycyclic aromatic hydrocarbon-DNA adducts in human placenta.

To determine the relative contributions of tobacco smoking and P-450 metabolism (cytochrome P-450IAI) in the formation of benzo(a)pyrenediol-epoxide and other polycyclic aromatic hydrocarbon-DNA adducts in vivo, 16 human placentas were assayed for aryl hydrocarbon hydroxylase activity and (+/-)r-7,t-8-dihydroxy-c-9,10-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene-DN A adduct levels. Immunoaffinity chromatography columns, conjugated with monoclonal antibodies raised against benzo(a)-pyrene-diol-epoxide-deoxyguanosine, were used to concentrate polycyclic aromatic hydrocarbon-DNA adducted nucleotides, and synchronous fluorescence spectroscopy was used specifically to detect r-7,t-8,t-9,c-10-tetrahydroxy-7,8,9,10-tetrahydrobenzo(a)pyrene (BP-tetrol) extracted from acid hydrolysates of immunoconcentrated materials. Data were analyzed for associations with maternal dietary and smoking habits, umbilical cord blood cotinine levels, and placental aryl hydrocarbon hydroxylase levels. Complex mixtures of fluorescent materials were present in organic solvent extracts of acid hydrolysates of immunoconcentrated nucleotide-adducts from all placentas with patterns of fluorescence that may be associated with tobacco smoking determined by generation of spectral fluorescence excitation-emission matrices. BP-tetrols were detected in extracts from 8 placentas: 5 of 7 from smokers and 3 of 9 from nonsmokers. Placental aryl hydrocarbon hydroxylase activity was significantly higher in placentas from which BP-tetrols were extracted [3.9 +/- 2.4 [corrected] (mean +/- SE) pmol 3-hydroxybenzo(a)pyrene mg protein-1 min-1], than among placentas from which BP-tetrols were not extracted (0.4 +/- 0.2 [corrected] pmol 3-hydroxybenzo(a)pyrene mg protein-1 min-1) (P = 0.03, Student's t test). This association was independent of maternal smoking or umbilical cord blood cotinine levels. These results indicate that while maternal tobacco smoking is associated with the accumulation of putative, but as yet unidentified, polycyclic aromatic hydrocarbon-DNA adducts in placenta, metabolic capacity appears to be the principal determinant for the (+/-)r-7,t-8-dihydroxy-c-9,10 epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene-DNA adduct levels detected.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗

Synthesis of human placental lactogen and human chorionic gonadotropin by polyribosomes and messenger RNA's from early and full term placentas.

Synthesis of human placental lactogen (hPL) and of human chorionic gonadotropin (hCG) by membrane-bound and free polyribosomes from early and from full term human placentas was investigated by in vitro release of the nascent hormone peptides, followed by immunoprecipitation and electrophoresis in sodium dodecyl sulfate gels, and by specific binding of 125I-labeled hPL antibody to nascent peptide chains. In addition, messenger RNA'S Were extracted from total, free, and membrane-bound placental polyribosomes and their capacities for hPL and hCG synthesis were measured in a heterologous cell-free system prepared from wheat germ. Membrane-bound polyribosomes from full term placentas were several times more active in the synthesis of both peptide hormones than were free polyribosomes. By binding 125I-labeled hPL antibody to nascent chains on the polyribosomes, it was determined that hPL is made by clusters of seven to nine ribosomes. About 8% of the nascent peptide chains released by incubation of polyribosomes from full term placentas was accounted for by hPL, and 2% by hCG. In contrast, no chains of hPL were released by polyribosomes from 10-week placentas, whereas 11% of the total released chains were accounted for by hCG. When messenger RNAs prepared from the polyribosomes of 20- and 40-week placentas were used to stimulate protein synthesis in a wheat germ system, hPL accounted for 0.4 and 2%, respectively, of total protein synthesis, while hCG was 8 and 2%, respectively. This confirmed the relative proportions observed for nascent chains on the polyribosomes of early and late placentas. Unexpectedly, translation of mRNA from free polyribosomes yielded as much hPL and two-thirds as much hCG as did translation of mRNA from bound polyribosomes. We conclude, that the decreased blood levels of hCG and increased blood levels of hPL with advancing gestational age reflect the relative in vitro rates of synthesis of these hormones by placental polyribosomes, the abundance of which is determined by availability of their respective messenger RNAs at different times in gestation.

Animals↗

Isolation and characterization of membrane-associated placental proteins.

Membrane-associated proteins (MPs) of the human term placenta (afterbirth) were obtained by extracting the insoluble part of the tissue with solubilizing agents, after the soluble material had been removed by washing with saline. The insoluble residue was subsequently exhaustively extracted first with the nonionic detergent Triton X-100 and then with 6 M urea. In the Triton extract eleven new different membrane-associated antigens could be detected by immunochemical methods; they were designated as MP2A to MP2L. One of these proteins (MP2C) was found to be immunochemically identical with the already described soluble placental protein PP21 [3]. MP1 another antigen detected in the Triton extract later was identified as heart stable alkaline phosphatase. In the urea extract eight different membrane-associated antigens could be identified by immunochemical methods; they were designated as MP3 to MP10. MP3 later was found to be immunochemically identical with laminin. All these membrane-associated proteins have now been isolated to purity and characterized by their physico-chemical properties. Specific antisera to the new proteins were obtained by immunizing animals with the corresponding purified proteins. They were used to detect and quantitate the new proteins in extracts of placentas and other human tissues by immunochemical methods such as gel diffusion tests. The immunocytochemical localization of the new proteins as well as measurement of their concentrations in body fluids by sensitive radioimmunoassays or enzyme immunoassays are presently under investigation.

Adult↗

Localisation and temporal changes in prostaglandin G/H synthase-1 and -2 content in ovine intrauterine tissues in relation to glucocorticoid-induced and spontaneous labour.

Parturition in the ewe is preceded by an increase in the synthesis of prostaglandins (PGs) by gestational tissues. To establish the uterine source of these PGs, placental cotyledons, fetal membranes and maternal uterine tissues were collected from ewes (n=6) at spontaneous parturition. Solubilised tissue extracts were prepared and analysed by Western blots using polyclonal antibodies to PG G/H synthase-1 and -2 (PGHS-1 and PGHS-2). PGHS-1 was expressed by all intrauterine tissues at term labour. Densitometric analysis of Western blot autoradiographs showed that the fetal membranes and maternal cervix contained the largest amounts of PGHS-1. PGHS-1 enzyme content of ovine amnion was significantly greater than that of either chorion or allantois (P<0.05). PGHS-1 protein content of myometrial, endometrial and cotyledonary tissue extracts was minimal. Formation of the PGHS-2 isozyme was confined to placental tissue at term labour. PGHS-2 protein levels in sheep placenta were significantly higher than those of PGHS-1 in all intrauterine tissues examined. This result supports the hypothesis that PGHS-2 is a major contributor to PG formation at term labour. To elucidate the developmental changes in PGHS-1 and PGHS-2 relative to labour onset, an experimental paradigm of glucocorticoid-induced delivery was used. Previous characterisation and validation of this labour model demonstrated that direct, transabdominal, intrafetal injection of the synthetic glucocorticoid betamethasone (5.7 mg in 1 ml aqueous vehicle) on day 131 of gestation induced labour onset in 56.6+/-0.8 h (mean+/-s.e.m.). As the latent period to induced-labour was known, the time course of enzyme formation could be ascertained. Sheep (n=20) were killed by barbiturate injection at various time intervals post-injection (0, 14, 28, 42 and 56 h). Tissue extracts collected at post-mortem examination were prepared and analysed by Western blots. PGHS-2 was induced in ovine cotyledon in a time-dependent fashion following glucocorticoid injection (P<0.05). There was a 12-fold increase in abundance between the time of betamethasone administration (0 h) and established labour (56 h). The PGHS-2 isozyme was not detected in any of the other tissues examined. In contrast, formation of the PGHS-1 isozyme did not change in relation to induced-labour in any of the intrauterine tissues. This finding is consistent with constitutive formation of PGHS-1. Previous studies have demonstrated a rise in PG production in association with glucocorticoid-induced labour and spontaneous delivery. The results of the present study indicate that this rise in PG production is due to increased formation of the PGHS-2 isozyme in ovine cotyledon. PGHS-2 appears to be induced by exogenous glucocorticoid administration and/or the mechanisms controlling ovine parturition. The role of PG formation by the fetal membranes is yet to be elucidated.

Analysis of Variance↗

Anticoagulant dermatan sulfate proteoglycan (decorin) in the term human placenta.

Normal pregnancy is characterized by increased in vivo thrombin generation. A greater proportion of endogenously generated thrombin is complexed to heparin cofactor II in plasma from pregnant women compared to plasma from nonpregnant ones. The increase in thrombin-heparin cofactor II complexes suggests that the site of the additional thrombin generation is relatively rich in dermatan sulfate. We postulated that the site of thrombin generation may be the placenta since endogenous thrombin generation returns rapidly to normal after delivery. This report describes the isolation and characterization of placental dermatan sulfate proteoglycan from villous tissue of the term human placenta. Placental dermatan sulfate was isolated by guanidine HCI extraction and anion exchange chromatography. The isolated material was found to have anticoagulant activity with a relative activity of approximately 40% of that of a porcine mucosal dermatan sulfate which is undergoing clinical trial as an antithrombotic agent. The dermatan sulfate was present as a proteoglycan with a molecular mass of 90-150 kD. Upon degradation with chondroitin ABC lyase, the core protein was demonstrated to be a doublet with molecular masses of 42 and 44 kD. This core protein reacted with antiserum against the core protein of decorin on Western analysis. The role of this placental dermatan sulfate in local regulation of thrombin in the placenta warrants further study.

Alcian Blue↗

Immunocytochemical localization and messenger ribonucleic acid concentrations for human placental lactogen in amnion, chorion, decidua, and placenta.

Human placental lactogen is one of the major hormones secreted by the placental syncytiotrophoblast and detected in the maternal circulation. Other sources of this hormone in intrauterine tissues at term have been sought by means of immunohistochemistry and northern analysis. Avidin-biotin immunoperoxidase staining with a specific polyclonal antibody to human placental lactogen showed this hormone to be present in groups of cells at the interface between chorionic cytotrophoblast and decidua parietalis and in some cells of the basal plate in addition to the classic source, the syncytiotrophoblast. Hybridization of polyadenylic-(+)ribonucleic acid extracted from amnion, chorion, decidua parietalis, basal plate, and placental trophoblast with a radiolabeled 48 mer oligonucleotide and a 540 base pair complementary deoxyribonucleic acid probe to human placental lactogen showed the placental trophoblast to be the major source of human placental lactogen and the extravillous chorion and basal plate to be additional minor sources.

Amnion↗

Liquid chromatography--tandem mass spectrometry analysis of cocaine and its metabolites from blood, amniotic fluid, placental and fetal tissues: study of the metabolism and distribution of cocaine in pregnant rats.

The ability to simultaneously quantitate cocaine and its 12 metabolites from pregnant rat blood, amniotic fluid, placental and fetal tissue homogenates aids in elucidating the metabolism and distribution of cocaine. An efficient extraction method was developed to simultaneously recover these 13 components using underivatized silica solid-phase extraction (SPE) cartridges. The overall recoveries for cocaine and its metabolites were studied from pregnant rat blood (47-100%), amniotic fluid (61-100%), placental homogenate (31-83%), and fetal homogenate (39-87%). Extraction of the samples using silica is not classical SPE, but rather allows for the concentration of the sample into a small volume prior to injection and the removal of the proteins due to their strong interaction with the active silica surface. A positive ion mode electrospray ionization liquid chromatography-tandem mass spectrometry (LC-MS-MS) method was used and validated to simultaneously quantitate cocaine and 12 metabolites from these four biological matrices. A gradient elution method with a Zorbax XDB C8 reversed-phase column was used to separate the components. Multiple reaction monitoring (MRM) of a product ion arising from the corresponding precursor ion was used in order to enhance the selectivity and sensitivity of the method. Low background noise was observed from the complex biological matrices due to efficient SPE and the selectivity of the MRM mode. Linear calibration curves were generated from 0.01 to 2.50 ppm. The method also showed high intra-day (n =3) and inter-day (n=9) precision (% RSD) and accuracy (% error) for all components. The limits of detection (LODs) for the method ranged from 0.15 to 10 ppb. The LODs of cocaine and its major metabolites were less than 1 ppb from all four biological matrices. This method was applied to the study of the metabolism and distribution of cocaine in pregnant rats following intravenous infusion to a steady state plasma drug concentration. The following results were observed in the pregnant rat study: (1) the observations correlated strongly with the previous literature data on cocaine metabolism and distribution, (2) cocaine and norcocaine accumulated in the placenta, (3) arylhydroxylation of cocaine was a major metabolic pathway, (4) para-arylhydroxylation of cocaine was favored over meta-arylhydroxylation in rats and (5) accumulation of cocaine and its major metabolites was observed in the amniotic fluid.

Amniotic Fluid↗

Atrial natriuretic hormone: a paracrine or endocrine role within the human placenta?

There is evidence to suggest that the human placenta may synthesize atrial natriuretic hormone (ANH). To test this hypothesis we examined specimens of normal term placenta obtained at elective caesarean section for evidence of either storage or synthesis of this peptide. No immunocytochemical or ultrastructural evidence of ANH storage was found. RNA extracted from cultured cytotrophoblast cells, the chorionic or decidual plates, or from placental villi contained no ANH-encoding messenger RNA by Northern blot analysis. Polymerase chain reaction amplification of these RNA extracts using primers directed to the midportion of the ANH gene failed to demonstrate any evidence of ANH-encoding RNA. We conclude that ANH is neither stored nor synthesized within the normal term placenta, and thus a purely endocrine role for this peptide within the fetoplacental compartment is proposed.

Atrial Natriuretic Factor↗

Cellular factor affecting the stability of beta-globin mRNA.

Messenger RNAs in eukaryotic cells exhibit a broad range of stabilities in vivo. Globin mRNA has a half life in excess of 50 h, but the half life of the c-myc oncogene mRNA is less than 20 min. Regulation of gene expression may be accomplished by a variety of mechanisms, including altering mRNA stability. We have examined the nuclear and cytoplasmic fractions of cells for factors affecting the metabolism of mRNA. Here we report that a HeLa whole-cell extract contains a factor that protects beta-globin mRNA from attack by RNases in a mouse erythroleukemia cell cytoplasmic extract. The factor is non-dialysable, inactivated by proteinase K and heat treatment, and resistant to RNase and DNase digestion. The HeLa cell factor resembles placental RNase inhibitor in that the mRNA-protecting activity is effective against RNase A and that treatment of the extract with N-ethylmaleimide completely destroys the protective activity. However, purified placental RNase inhibitor was unable to inhibit the RNase activity in the MELC cytoplasmic extract. These results suggest that the HeLa cell extract contains an RNase inhibitor (or inhibitors) with an activity or specificity that is distinct from that of placental RNase inhibitor.

Cell Line↗

Purification of decidual prolactin-releasing factor, a placental protein that stimulates prolactin release from human decidual tissue.

Decidual prolactin-releasing factor (PRL-RF), a placental protein that stimulates the release of prolactin from human decidual tissue, has been purified from conditioned medium of human placental explants. The purification scheme consisted of ethanol extraction, anion exchange chromatography on DEAE-cellulose, size exclusion chromatography on Spherogel TSK-3000, and either a) immunoaffinity chromatography using an antiserum to a partially purified PRL-RF preparation or b) acetic acid-urea/SDS 2-dimensional PAGE. The apparent molecular weight of the purified releasing factor, estimated by SDS-PAGE, was 23,500 Da; and the half-maximal dose for the acute stimulation of prolactin release from human decidual cells was 0.05-0.1 ug/ml (2.2-4.4 nM).

Biological Assay↗

The use of needle biopsy for assessment of placental gene expression.

OBJECTIVE: The purpose of this study was to test the hypothesis that placental samples that are obtained by needle aspiration ex vivo are useful for the determination of villus gene expression. STUDY DESIGN: Placental biopsy was performed with a spinal needle after uncomplicated deliveries. Villi were inspected microscopically, and RNA was extracted and analyzed with capillary electrophoresis. Gene expression was determined with quantitative polymerase chain reaction. RESULTS: We obtained more placental villous fragments per aspiration using a 20-gauge needle (5.2 +/- 1.8 fragments) than with a 22-gauge needle (3.3 +/- 1.6 fragments; P < .01). RNA quality was adequate, based on the 28S and 18S recombinant RNA bands, with a mean 260/280 ratio of 1.88. The amount of extracted RNA correlated with the number of villous fragments per aspirate. Importantly, the expression of NDRG1 and hPL, both markedly altered in hypoxia, was consistent between villi that were obtained by either needle or standard biopsy. CONCLUSION: Placental samples that are obtained by ex vivo needle aspiration are useful for the extraction of RNA and for the determination of villous gene expression.

Biopsy, Needle↗

Distribution of lactate dehydrogenase isoenzymes in coelomic fluid and fetal adnexae.

The objective of this study was to evaluate the distribution of lactate dehydrogenase isoenzymes in the human gestational sac. Total lactate dehydrogenase and its isoenzymes were measured in matched coelomic fluid and samples of villous and decidual tissues collected at the time of pregnancy termination in a group of 16 healthy women who were between 7 and 12 weeks of gestation. In addition intact secondary yolk sacs (n = 2) and fragments of fetal liver (n = 3) were collected. For comparison, samples of placental tissue, amniotic membrane and chorion obtained at term, were also investigated. In early pregnancy, H-type lactate dehydrogenase isoenzymes predominate in placental villous tissue and coelomic fluid, whereas M-type lactate dehydrogenase isoenzymes predominate in extracts of decidua, secondary yolk sac and fetal liver. These results highlight the important contribution of placental bioproducts to the constitution of the coelomic fluid. We observed also that placental patterns of lactate dehydrogenase isoenzymes change between the first and the third trimester of gestation, from the H-type to the M-type lactate dehydrogenase isoenzymes. We suggest that the lactate dehydrogenase pattern might be an indicator of proliferative or differentiative potential of the trophoblastic cells throughout pregnancy.

Adnexa Uteri↗

Effects of nitric oxide donors and inhibitors of nitric oxide signalling on endothelin- and serotonin-induced contractions in human placental arteries.

In order to explore the role of nitric oxide (NO) in the control of fetoplacental vascular tone in normal pregnancy we have examined the effects of NO donors on uteroplacental arteries pre-contracted with the vasoconstrictor endothelin-1 (ET-1) or serotonin (5-HT). We have furthermore examined the effects of guanylate cyclase inhibitors on the NO-induced relaxation. Segments of placental arteries (n=102) obtained from 39 placentas immediately after delivery were mounted in organ baths and superfused with Krebs-Ringer solution at 37 degrees C. The vessel segments were exposed to drugs for various intervals and the tension was recorded isometrically and registered on a polygraph. Cyclic guanosine monophosphate (cGMP) analysis was performed after extraction of vessel segments using a specific radioimmunoassay. The placental artery segments responded to ET-1 and 5-HT with a dose-dependent vasoconstriction. After pre-contraction with ET-1 (10(-7) M) or 5-HT (10(-6) M), the vessels relaxed in response to the NO donors glyceryltrinitrate (GTN) (10(-6) M) and S-nitroso-N-acetyl-penicillamine (SNAP) (10(-5) M). In the presence of the non-specific guanylate cyclase inhibitor LY 83583 (10(-6) M), the vessels responded with a small contraction. In the presence of the soluble guanylate cyclase (sGC) inhibitor 1H[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) the non-treated vessels responded with a relaxation. 1H[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one gave no obvious relaxation in pre-contracted vessels. Addition of 8-Br-cGMP, the cell-permeant analogue of cGMP, with or without pre-contraction had no effect on the vessels. Cyclic guanosine monophosphate analysis showed that GTN treatment caused an increase in cGMP after 12 min. Our results indicate that NO acts as a vasodilator in placental vessels. The cGMP-dependent mechanisms may be involved in NO-induced relaxation but cGMP-independent mechanisms appear also to be involved.

Adult↗

Demonstration of intracellular and secreted forms of large human chorionic gonadotrophin alpha subunit in cultures of normal placental tissue.

Free human chorionic gonadotrophin (hCG) alpha-subunit in tissue extracts and incubation media of normal placentae before and after four days of culture was investigated by Sephadex G-100 chromatography. Prior to incubation, tissue extracts of first-trimester and term placentae contained a large form and a small form of alpha-subunit relative to a reference urinary hCG alpha-subunit preparation. The large alpha-subunit comprised 30.6 +/- 1.4 per cent s.e.m. and the small alpha-subunit, 66.9 +/- 4.1 per cent of total intracellular alpha-subunit. After 96 h of incubation, the large alpha-subunit comprised 77.6 +/- 9.8 per cent of the total intracellular alpha-subunit, and the small 21.0 +/- 8.1 per cent. The incubation medium contained a single form of alpha-subunit which eluted with a larger apparent molecular weight than the urinary hCG alpha-subunit. Following neuraminidase treatment, the large alpha-subunit from tissue extracts eluted as a smaller molecule in the position of the urinary hCG alpha reference. A change in Ve/Vo of the small alpha-subunit was not detected. Identical neuraminidase treatment of the large alpha-subunit from incubation medium resulted in an increase in the Ve/Vo, but the large alpha-subunit continued to elute from Sephadex G-100 before the urinary hCG alpha-subunit. However, large alpha-subunit from culture medium did elute in the position of urinary hCG alpha following mild acid hydrolysis. These studies demonstrate that a large form of alpha-subunit is present in first-trimester and term placental tissue both before and after incubation in vitro and that the large form of alpha-subunit is secreted by the normal placenta. The differential effects of neuraminidase treatment on the intra- and extracellular forms of large alpha-subunit coupled with our findings from acid hydrolysis of the extracellular form suggest that alpha-subunit secreted into the culture medium may contain additional carbohydrate residues not present on the intracellular form.

Choriocarcinoma↗

LHRH-like immunoreactivity in the human placenta is not identical to LHRH.

LHRH-like immunoreactive material was separated from human placental homogenates by chromatography and tested against two antibodies directed respectively against the C- or the N-terminus (N- and C-antibodies) of the synthetic peptide. Extraction yield was 94 per cent as assessed by the recovery of the radiolabelled LHRH added to the homogenates. Placental LHRH-like immunoreactivity in crude extracts appeared largely overestimated, due to interference of endogenous substances non-related to LHRH. After elimination of this contamination, a higher residual activity was detected with the C- than with the N-antibodies. Eluates tested under these conditions contained only 550 pg of LHRH-like material per kg of placenta. This concentration was comparable whether placental tissue had been sampled at 12 weeks of pregnancy or at the end of gestation. The corresponding peptides however neither co-eluted with synthetic LHRH nor with catabolite fragments of the peptide. It is concluded that the human placenta contains a lesser amount of LHRH-like material than anticipated on the basis of earlier results and that this material does not correspond to the native decapeptide.

Antibody Specificity↗

Effect of restriction of placental growth on oxygen delivery to and consumption by the pregnant uterus and fetus.

Endometrial caruncles were excised from 13 sheep (caruncle sheep) before pregnancy to restrict placental growth. In subsequent pregnancies, half the caruncle fetuses were growth retarded or small (weight more than 2 SD below mean weight for control fetuses) with the remainder, normal-sized (weight within 2 SD of mean weight for control fetuses). The caruncle and 16 control sheep, each with indwelling vascular catheters, were studied between 121 and 130 days of pregnancy. Oxygen delivery to and consumption by the pregnant uterus in caruncle sheep with small fetuses was significantly reduced compared to controls while oxygen extraction was significantly increased. Oxygen tension (P02) and content in the common umbilical vein and in the descending aorta were significantly lower in small caruncle fetuses compared to controls but only P02 was lower in normal-sized caruncle fetuses. Oxygen delivery to, and consumption by, the fetus was significantly reduced in normal-sized and in small caruncle sheep compared to controls while oxygen extraction was increased in small caruncle sheep. Utero-placental oxygen consumption was significantly lower in caruncle sheep with small fetuses compared to that in controls. Despite these changes, oxygen consumption by the gravid uterus and fetus, per kg of tissue mass, was similar in both groups of caruncle and in control sheep. Utero-placental oxygen consumption per kg of utero-placental mass in caruncle sheep with small fetuses was not significantly different to that in sheep with normal-sized caruncle or control fetuses, although it averaged only 25% of that in controls. It is concluded that intrauterine growth retardation following restriction of placental growth is associated with a reduced supply of oxygen to both the pregnant uterus and fetus and a redistribution of oxygen to the fetus. This is due to the disproportionate maintenance of fetal growth relative to that of the placenta, since oxygen consumption by either, in terms of tissue mass, was not altered. Further, the greater uterine and fetal extraction of oxygen suggests that a smaller margin of safety may exist between supply and demand in intrauterine growth retardation.

Animals↗