Iron and copper concentrations in the maternal and fetal serum, placenta and amniotic fluid during the reproductive stadium as well as in the milk of rabbits

Serum concentrations of iron and copper from rabbits (New Zealand White hybrids; N = 12) were determined during the reproductive stadium (gestation and four weeks of lactation). Samples of serum from fetuses, placental tissue and amniotic fluid were also examined. Iron: a decrease of iron in the maternal serum during the second half of gestation was observed, whilst a significant rise occurred in the first week of lactation. The content of iron in the fetal serum dropped from day 21 to day 28 of gestation. The iron concentration in the placental tissue decreased during this time. A rise of the iron level in the amniotic fluid was determined from day 21 to day 28 of gestation. The iron content in the milk was about 33 mumol/l (first and second day of lactation). Copper: in the first half of pregnancy the copper level diminished slightly compared with the content of non-pregnant, non-lactating rabbits, while a rise was observed in the fourth week of this period. The copper concentration decreased in the first week of lactation and then reached the peak level in the second week of this phase. The copper level in the fetal serum declined from day 21 to day 28 of gestation, while the copper content in the amniotic fluid increased significantly on day 28, in comparison with day 21 of gestation. In contrast, a decline of the copper concentration in the placental tissue was noticed from day 21 to day 28 of this period. The copper content in the milk was nearly 25 mumol/l (first and second day of lactation).     

Diagnosis and monitoring of pregnancy in mice: correlations between maternal weight, fetal and placental mass and the maternal serum levels of progesterone, pregnancy-associated murine protein-2 and alpha-fetoprotein

Outbred Bom:NMRI mice were weighed daily for 18 days from observation of a vaginal plug. In a separate experiment, fetuses and placentae were weighed on each day of pregnancy. Pregnancy can be determined with 99% certainty on day 12 of gestation by the maternal body weight increase from day 1. The pregnancy-specific proteins alpha-fetoprotein (m-AFP) and pregnancy-associated murine protein-2 (PAMP-2), of fetal and placental origin respectively, were detectable on days 8 and 10 in the maternal circulation. Significant correlations were observed between m-AFP and fetal weight and PAMP-2 and placental weight. These markers may therefore be useful in the monitoring of fetal growth and placental growth respectively.     

Metabolic response to starvation in late pregnant rats. II. Fetal response

Effect of prolonged maternal fasting on the fetal liver and heart glycogen and triglyceride content and on concentration of glucose, urea, uric acid and alpha amino-nitrogen in the amniotic fluid has been studied in rats. The animals were divided into four groups: fed (control), fasted for one day (from 20 to 21 day of pregnancy), fasted for two days (from 19 to 21 day) and fasted for three days (from 18 to 21 day). Maternal fasting for two and three days resulted in reduction in fetal growth. The fetal liver glycogen content was reduced already after one day of fasting, stabilized after two days and then further decreased after three days. The fetal heart glycogen content was reduced only after three days of fasting. The fetal liver triglyceride content increased gradually during the first two days of fasting and then stabilized. The content of triglycerides in the heart was elevated after two and three days of food deprivation. The amniotic fluid glucose concentration decreased after one day of fasting and then stabilized. Fasting did not effect the concentration of the nitrogenous compounds in the amniotic fluid. It is concluded that maternal fasting affects markedly metabolism of energy substrates stored in the fetal liver and the heart and the composition of the amniotic fluid.     

Early treatment of the pregnant guinea pig with IGFs promotes placental transport and nutrient partitioning near term

Appropriate partitioning of nutrients between the mother and conceptus is a major determinant of pregnancy success, with placental transfer playing a key role. Insulin-like growth factors (IGFs) increase in the maternal circulation during early pregnancy and are predictive of fetal and placental growth. We have previously shown in the guinea pig that increasing maternal IGF abundance in early to midpregnancy enhances fetal growth and viability near term. We now show that this treatment promotes placental transport to the fetus, fetal substrate utilization, and nutrient partitioning near term. Pregnant guinea pigs were infused with IGF-I, IGF-II (both 1 mg.kg-1.day-1) or vehicle subcutaneously from days 20-38 of pregnancy (term=69 days). Tissue uptake and placental transfer of the nonmetabolizable radio analogs [3H]methyl-D-glucose (MG) and [14C]aminoisobutyric acid (AIB) in vivo was measured on day 62. Early pregnancy exposure to elevated maternal IGF-I increased placental MG uptake by>70% (P=0.004), whereas each IGF increased fetal plasma MG concentrations by 40-50% (P<0.012). Both IGFs increased fetal tissue MG uptake (P<0.048), whereas IGF-I also increased AIB uptake by visceral organs (P=0.046). In the mother, earlier exposure to either IGF increased AIB uptake by visceral organs (P<0.014), whereas IGF-I also enhanced uptake of AIB by muscle (P=0.044) and MG uptake by visceral organs (P=0.016) and muscle (P=0.046). In conclusion, exogenous maternal IGFs in early pregnancy sustainedly increase maternal substrate utilization, placental transport of MG to the fetus, and fetal utilization of substrates near term. This was consistent with the previously observed increase in fetal growth and survival following IGF treatment.     

Arginine nutrition and fetal brown adipose tissue development in diet-induced obese sheep

The global incidence of human obesity has more than doubled over the past three decades. An ovine model of obesity was developed to determine effects of maternal obesity and arginine supplementation on maternal, placental, and fetal parameters of growth, health, and well being. One-hundred-twenty days prior to embryo transfer, ewes were fed either ad libitum (n?=?10) to induce obesity or 100% National Research Council-recommended nutrient requirements (n?=?10) as controls. Embryos from superovulated ewes with normal body condition were transferred to the uterus of control-fed and obese ewes on day 5.5 post-estrus to generate genetically similar singleton pregnancies. Beginning on day 100 of gestation, obese ewes received intravenous administration of saline or L-arginine-HCl three times daily (81?mg arginine/kg?body?weight/day) to day 125, whereas control-fed ewes received saline. Fetal growth was assessed at necropsy on day 125. Maternal obesity increased (1) percentages of maternal and fetal carcass lipids and (2) concentrations of leptin, insulin, glucose, glutamate, leucine, lysine and threonine in maternal plasma while reducing (1) concentrations of progesterone, glycine and serine in maternal plasma and (2) amniotic and allantoic fluid volumes. Administration of L-arginine to obese ewes increased arginine and ornithine concentrations in maternal and fetal plasma, amniotic fluid volume, protein content in maternal carcass, and fetal brown adipose tissue (+60%), while reducing maternal lipid content and circulating leptin levels. Fetal or placental weight did not differ among treatments. Results indicate that arginine treatment beneficially reduces maternal adiposity and enhances fetal brown adipose tissue development in obese ewes.     

Pregnancy-specific protein B (PSPB), progesterone and some biochemical attributes concentrations in the fetal fluids and serum and its relationship with fetal and placental characteristics of Iraqi riverine buffalo (Bubalus bubalis)

This study was carried out to demonstrate the pregnancy-specific protein B (PSPB), progesterone and some biochemical parameters concentrations in amniotic fluid, allantoic fluid and fetal serum collected from slaughtered Iraqi riverine pregnant buffaloes at three different months of gestation (6th, 7th and 8th). Ten out of 22 adult buffaloes of 4.6 ± 0.97 years old were used in this study. The buffaloes were mated naturally by monitoring the estrus cycles via appearance of vaginal fluids and mounting by bulls. Pregnancy was checked for these buffaloes by non-returning to estrus for three estrus cycles and assured by rectal palpation on day 61 post-mating (PM). Buffaloes were slaughtered at three different periods of gestation (three at 6th month, four at 7th month and three at 8th month of gestation) to verify the progesterone and PSPB as well as some blood attributes levels (glucose, cholesterol, total protein, albumin, globulins and albumin: globulins ratio) in amniotic fluid (AF), allantoic fluid (LF) and fetal serum (FS). Progesterone was higher (P<0.01) in LF at the 8th month of gestation and lower in FS during the 7th and 8th months of pregnancy. PSPB concentrations were greater in FS (6th and 8th months in particular) than in both AF and LF. The overall mean of cholesterol concentration was higher in FS (P<0.05) followed by AF and LF that had the lowest concentration. The FS exhibited higher total protein during the three gestation periods. Most of fetal and placental measurements increased as the pregnancy advanced. In conclusion, these results described, for the first time, the PSPB and progesterone concentrations and blood characteristics in fetal fluids and serum in water riverine buffaloes during different stages of pregnancy. Progesterone concentrations were greater in allantoic fluid than in other fluids. In contrast, PSPB and other blood attributes were higher in fetal serum than other fluids of Iraqi riverine buffaloes. These findings reflect the changes in hormones, proteins and other metabolites during different gestation periods.     

alpha-Fetoprotein values in monkey (Macaca mulatta) pregnancy.

The pregnant rhesus monkey's (Macaca mulatta) potential as a model for understanding the dynamics of alpha-fetoprotein (AFP) metabolism in human pregnancy was evaluated. AFP levels in maternal and fetal serum and amniotic fluid were determined by radioimmunoassay. Significant correlations were found between decreasing maternal serum, fetal serum and amniotic fluid AFP concentrations and increasing gestational age. However, these data are not consistent with the AFP changes reported in human pregnancy. It appears that this animal has limited applicability as a model in this aspect of human pregnancy.     

Chronic alterations in ovine maternal corticosteroid levels influence uterine blood flow and placental and fetal growth

Previous work from this laboratory demonstrated that the elevation of maternal plasma corticosteroid concentrations during pregnancy is important for the support of fetal development. Reducing ovine maternal plasma cortisol concentrations to nonpregnant levels stimulates homeostatic responses that defend fetal blood volume. The present study was designed to test the hypothesis that chronic decreases or increases in maternal plasma cortisol concentration alter uterine and placental blood flow and morphology. Three groups of pregnant ewes and their fetuses were chronically catheterized and studied: ewes infused with cortisol (1 mg.kg(-1).day(-1); high cortisol), ewes adrenalectomized and underreplaced with cortisol (0.5 mg.kg(-1).day(-1); low cortisol), and control ewes. The normal increment in uterine blood flow between 120 and 130 days was eliminated in the low-cortisol ewes; conversely, uterine blood flow was increased in the high-cortisol group compared with the control group. Fetal arterial blood pressure was increased in the high-cortisol group compared with controls, but there was no increase in fetal arterial pressure from 120 to 130 days of gestation in the low-cortisol group. The fetuses of both low-cortisol and high-cortisol groups had altered placental morphology, with increased proportions of type B placentomes, and overall reduced fetal placental blood flow. The rate of fetal somatic growth was impaired in both low-cortisol and high-cortisol groups compared with the fetuses in the intact group. The results of this study demonstrate that maternal plasma cortisol during pregnancy is an important contributor to the maternal environment supporting optimal conditions for fetal homeostasis and somatic growth.     

Reduced fetal, placental, and amniotic fluid PTHrP in the growth-restricted spontaneously hypertensive rat

Evidence implicates pivotal roles for parathyroid hormone-related protein (PTHrP) in stimulating cell growth and differentiation, placental calcium transport, and placental vasodilatation. As spontaneously hypertensive rat (SHR) fetuses are growth restricted compared with those of its normotensive control, the Wistar Kyoto (WKY) rat, we examined intrauterine PTHrP and total and ionic calcium concentrations in these rats. Fetal plasma PTHrP concentrations, but not total calcium concentrations, were lower in the SHR compared with WKY (P < 0.05). SHR placental concentrations of PTHrP were lower than in WKY (P < 0.03) and failed to show the increase observed in WKY near term (P < 0.05). PTHrP concentrations in amniotic fluid from SHR were not raised near term and were lower compared with WKY (P < 0.0005). The increased ionic calcium concentrations in amniotic fluid in the WKY near term (P < 0.05) were not detected in the SHR. Thus SHR fetal plasma, placental, and amniotic fluid PTHrP concentrations were reduced and associated with fetal growth restriction. We suggest that PTHrP may play a role in the etiology of both growth restriction during pregnancy and hypertension later in life.     

Fetomaternal adrenomedullin levels in diabetic pregnancy.

We investigated whether maternal and fetoplacental adrenomedullin, a newly discovered hypotensive peptide involved in the insulin regulatory system, is modified in diabetic pregnancy. We studied its correlation with pregnancy complications associated with this disease. Thirty-six pregnant women with diabetes (13 with type I and 23 with gestational diabetes mellitus) and in 40 uncomplicated pregnancies were included. 10 out of 36 diabetic pregnancies were complicated by gestational hypertension. In each woman, adrenomedullin concentration in maternal and fetal plasma and in amniotic fluid was assessed by specific radioimmunoassay. We found that overall mean amniotic fluid adrenomedullin concentration was higher (p < 0.05) in diabetic (14.7 +/- 1.6 fmol/ml) than in uncomplicated pregnancies (10.8 +/- 0.9 fmol/ml), whereas no differences were present in maternal and fetal plasma adrenomedullin levels between diabetic and uncomplicated pregnant women. High levels of amniotic fluid adrenomedullin were found in both type I and gestational diabetes mellitus pregnancies (13.7 +/- 1.4 and 15.6 +/- 2.2 fmol/ml, respectively). Diabetic pregnancies complicated by gestational hypertension showed lower (p < 0.05) amniotic fluid adrenomedullin concentrations than normotensive diabetic patients. These findings suggest that placental adrenomedullin production is upregulated in diabetic pregnancy, and it may be important to prevent excessive vasoconstriction of placental vessels.     

Arachidonic acid metabolism by bovine placental tissue during the last month of pregnancy

Conversion of tritiated arachidonic acid (AA) into metabolites of the cyclo- and lipoxygenase pathways by bovine fetal placental tissue (200 mg) and fetal plus maternal placental tissue (400 mg) of Days 255, 265, 275 of gestation and at parturition (n = 5) during a 30 min incubation was measured using reverse-phase high pressure liquid chromatography. Fetal placental tissue produced 13,14-dihydro-15-keto-prostaglandin E2 (PGEM) as the major metabolite, the synthesis of which increased from Day 265 to Day 275 and parturition by 150% and 475%, respectively. In tissues collected at parturition, PGE2 synthesis was also detected. On Day 275 and at parturition fetal placental tissue synthesized the metabolite 12-hydroxyheptadecatrienoic acid (HHT), and throughout the experimental period the lipoxygenase product 15-HETE was detected with synthesis rates increasing over time of gestation. In addition, an unidentified metabolite was regularly found in the radiochromatograms which eluted at 1 h and 1 min (U101), between HHT and 15-HETE. The synthesis of this metabolite decreased as pregnancy progressed. Furthermore, various other polar and nonpolar metabolites pooled under the heading UNID were eluted, the production of which increased over time of gestation. The presence of maternal placental tissue did not influence the synthesis of PGEM, 15-HETE and U101, but the production of HHT was decreased when maternal tissue was present. Also, as pregnancy progressed, maternal placental tissue seemed to contribute to the pool of unidentified metabolites. In conclusion, fetal placental tissue seems to be the major source of the AA metabolites when compared with maternal placental tissue, and AA metabolism by bovine placental tissue is markedly increased throughout the last month of pregnancy, suggesting a role for AA metabolites in mechanisms controlling parturition.     

Iron metabolism and placental iron transfer in the guinea pig

The interrelationship between fetal iron uptake and maternal iron metabolism has been studied in the guinea pig in the course of pregnancy. The rapid increase of the maternal need for iron during the period of fast increasing rates of placental iron transfer is largely compensated for by increased intestinal absorption. No enhanced mobilisation of iron from the liver and spleen iron stores could be demonstrated. The plasma iron turnover, corrected for the transplacental iron transfer rate, remained constant during pregnancy. This means that not only the mobilisation of iron from the stores remains principally unchanged, but also the supply of iron to the maternal organs and tissues. The haemoglobin concentration decreased by about 15% during the period of rapid fetal growth and iron uptake. The maternal blood volume increased during this very period and explained most of the observed reduction. Intestinal iron absorption increases. At day 55 of pregnancy placental iron transfer is maximal. It could be shown that a day 55 the rate of intestinal iron uptake equals the rate of iron transfer across the placentas. It is evident that pregnancy effects a direct influence on intestinal iron absorption, independent of the magnitude of the maternal iron stores. How this influence is realized without changing the iron kinetics of the maternal stores, cannot be explained with the prevailing theory.     

THE NATURE AND ORIGIN OF THE SOLUBLE PROTEIN IN HUMAN AMNIOTIC FLUID

1. Amniotic fluid surrounds the human fetus and is separated from the uterus by the amnion, chorion and placenta. The ability to obtain samples of amniotic fluid from women by a simple procedure has encouraged studies on the nature and origin of the fluid, and on its use for the diagnosis of a variety of clinical conditions. The fluid contains cells, which are of fetal origin, and can be grown in a tissue culture. Cyto-genetic and biochemical analyses can therefore be used to detect chromosomal aberrations and inborn errors of metabolism in the fetus. 2. The supernatant of amniotic fluid contains many of the solutes typical of extracellular fluid. In particular, it contains a wide range of proteins and those which are of fetal origin are likely to be of use in the prenatal diagnosis of fetal disease. This review examines the nature and origin of the soluble protein in amniotic fluid, and discusses the diagnostic uses of the proteins which are of fetal origin. 3. In other mammals, the arrangement of the fetal membranes is different from that in man, and these differences are reflected by changes in the nature of the amniotic fluid. Thus data from other animals have little applicability to man. 4. Electrophoresis and immunoelectrophoresis have established that the major proteins in amniotic fluid are also present in maternal and fetal sera. Their concentrations in the fluid are influenced by their molecular weight and proteins larger than about 2.5 times 10⁶ may be excluded. Towards term, phenotyping studies show that a number of serum proteins in amniotic fluid are of maternal origin. In the case of group-specific component (Gc) this has been shown to be so throughout pregnancy. Such proteins must enter the fluid by diffusing across either the chorion or the chorionic plate and then the amnion. 5. It has been previously claimed that various serum proteins in amniotic fluid are of fetal origin. For albumin and IgG there are data that strongly support a maternal origin. The evidence on the origin of insulin is inconclusive. The concentration of β₂-microglobulin in amniotic fluid exceeds that in maternal serum and is probably too high also for fetal serum to be its major source. It has a wide tissue distribution and probably enters the fluid from surrounding structures. 6. Alpha-fetoprotein in amniotic fluid is of fetal origin as it is present in maternal serum at far lower concentrations. It is found in fetal serum, urine and yolk sac, but it is not clear how it enters the amniotic fluid of normal fetuses. The concentrations of Gc and alpha-fetoprotein have been measured in amniotic fluid and in their sera of origin. The relative concentration of Gc in amniotic fluid was found to be much greater than that of alpha-fetoprotein and the concentration gradients of these marker proteins can be compared with data for other proteins. In this way further evidence has been obtained that the albumin, α₁,-antitrypsin and transferrin in amniotic fluid are mainly of maternal origin throughout pregnancy. 7. Immunological studies have shown that at least three proteins of non-serum origin are present in amniotic fluid and they have also been located in the amnion and uterine decidua. 8. The enzymes present in amniotic fluid are summarized. Many lysosomal enzymes are clearly of fetal origin since they show altered specific activities in the appropriate cases where the fetus is affected with an inborn error of metabolism. For other enzymes, analysis of specific activity gradients can help to decide the extent to which an enzyme is of serum origin, although this will not exclude the possibility of a maternal (uterine) contribution. The results of such analyses suggest that, relative to the serum protein in amniotic fluid, the greatest concentrations of the minor non-serum proteins in the fluid occurs between thirteen and eighteen weeks of pregnancy and also towards term. 9. Some inborn errors of metabolism may be diagnosed prenatally by measuring the specific activity of the respective enzyme in amniotic fluid. However, the presence of different enzymes with similar substrate specificities has prevented this in Pompe's disease. 10. In cases where the fetus is affected with anencephaly or spina bifida there is an increase in the concentration of alpha-fetoprotein in the amniotic fluid. This has provided a way of detecting these diseases early enough to allow termination of pregnancy. 11. The discovery of new proteins in fetal serum and in the tissues surrounding the amniotic cavity would seem to provide the best chance of extending the uses of amniotic fluid into the other areas of prenatal medicine.     

Protein restriction in early pregnancy alters fetal and placental growth and allantoic fluid proteins in swine

This study was designed to determine the impact of protein malnutrition during early pregnancy on fetal and placental growth and on the protein synthesis capacity of placental and endometrial tissues. Twelve crossbred sows received 1.8 kg/d of a control (13% protein) or protein-restricted (0.5% protein) diet from the day of breeding to Day 63 of pregnancy, when dissections were performed on each conceptus unit. The de novo protein synthetic rate of placental and endometrial explants was measured using (35)S-methionine. These proteins and the proteins from amniotic and allantoic fluids were separated by polyacrylamide gel electrophoresis. Placental weight was significantly reduced in the sows fed the restricted diet, with a tendency for decreased fetal weight as well. No differences were found due to dietary treatment in de novo protein synthesis or in the electrophoretic patterns of secreted proteins of the placenta or endometrium. The apparent quantity of 3 proteins in the allantoic fluid of the restricted diet fetuses decreased, while 1 protein increased in comparison with that of the control fetuses. These data suggest that protein malnutrition in early pregnancy decreases placental growth, thereby decreasing both fetal growth and the opportunity for compensatory growth upon nutritional rehabilitation.     

Hormonal and physical changes associated with bovine conceptus development.

Conceptus (placental membranes, fetal fluids and fetus) development was characterized between Days 27 and 111 of gestation. Progestagens, oestrone, oestradiol, oestrone sulphate and prostaglandins (PG) F were measured in maternal plasma and allantoic and amniotic fluids. Protein concentrations are described for fetal fluids. The early increase in placental membrane weight from 1.12 g (27 days) to 58.45 g (50 days) was associated with oestrogen production presumably of conceptus origin. Oestrogens increased significantly in allantoic and amniotic fluids throughout the period studied with oestrone being the primary free oestrogen, rising from 2 pg/ml (Day 33) to 144 ng/ml by 111 days in allantoic fluid. Changes in plasma oestrogens of the maternal circulation were not detected until after Day 70 at which time oestrone concentration was greater than that of oestradiol. Fetal fluid concentrations of progestagens, oestrone sulphate and PGF were not related to maternal plasma levels and a sequestration of these hormones by the allantois is postulated.     

Uteroplacental restriction in the rat impairs fetal growth in association with alterations in placental growth factors including PTHrP

During pregnancy, parathyroid hormone-related protein (PTHrP) is one of many growth factors that play important roles to promote fetal growth and development, including stimulation of placental calcium transport. Angiotensin II, acting through the AT(1a) receptor, is also known to promote placental growth. We examined the effects of bilateral uterine artery and vein ligation (restriction), which mimics placental insufficiency in humans, on growth, intrauterine PTHrP, placental AT(1a), and pup calcium. Growth restriction was surgically induced on day 18 of pregnancy in Wistar-Kyoto female rats by uterine vessel ligation. Uteroplacental insufficiency reduced fetal body weight by 15% and litter size (P < 0.001) compared with the control rats with no effect on placental weight or amniotic fluid volume. Uteroplacental insufficiency reduced placental PTHrP content by 46%, with increases in PTHrP (by 2.6-fold), parathyroid hormone (PTH)/PTHrP receptor (by 11.6-fold), and AT(1a) (by 1.7-fold) relative mRNA in placenta following restriction compared with results in control (P < 0.05). There were no alterations in uterine PTHrP and PTH/PTHrP receptor mRNA expression. Maternal and fetal plasma PTHrP and calcium concentrations were unchanged. Although fetal total body calcium was not altered, placental restriction altered perinatal calcium homeostasis, as evidenced by lower pup total body calcium after birth (P < 0.05). The increased uterine and amniotic fluid PTHrP (P < 0.05) may be an attempt to compensate for the induced impaired placental function. The present study demonstrates that uteroplacental insufficiency alters intrauterine PTHrP, placental AT(1a) expression, and perinatal calcium in association with a reduction in fetal growth. Uteroplacental insufficiency may provide an important model for exploring the early origins of adult diseases.     

Normal concentrations of essential and toxic elements in pregnant baboons and fetuses (Papio species)

Heavy metals are essential for the normal progression of maternal and fetal tissue growth and metabolism in pregnancy. Considerable data have been collected for concentrations of various elements in pregnant women, but no comprehensive evaluation of element concentrations in any non-human primate model has been performed. Baboons were studied at the second half of pregnancy. Forty essential and toxic element concentrations were analyzed by absorption spectrophotometry in paired maternal and fetal blood samples; hair and nail samples in pregnant baboons; in placenta, amniotic fluid; and fetal femur, lymph nodes, and liver. Concentrations demonstrated an excellent correlation with concentrations reported in late human pregnancy. Twenty-four elements were below detectable limits in various specimens. We conclude that the pregnant baboon offers unique opportunities to study both normal maternal, fetal, and placental physiology as well as the environmental toxicology of these elements. This information and the ability to use the pregnant baboon as a model is important because essential and toxic elements are key components of the diet as well as major products of manufacturing processes within our industrialized society.     

Expression of the corticotropin-releasing hormone (CRH) gene in human placenta and amniotic membrane

Immunoreactive corticotropin-releasing hormone (IR-CRH) in maternal plasma increases progressively during pregnancy and decreases rapidly after delivery, suggesting that IR-CRH is produced in the placenta. We studied the expression of the CRH gene in developing human chorionic tissue, the amniotic membrane, the uterine myometrium and a fresh surgical specimen of hydatidiform mole by Northern blot analysis. Our results were as follows: (1) CRH mRNA was demonstrated in the placenta in the third trimester and at term, but under detectable level in the first and second trimesters. (2) CRH mRNA expression was observed in the amniotic membrane, but its expression in the myometrium in normal pregnancy was under detectable level at term. (3) CRH mRNA was also under detectable level in trophoblasts of a hydatidiform mole. These results suggest that the sources of the increased level of IR-CRH in human plasma and amniotic fluid during pregnancy are the placenta and amniotic membrane, and that gene expression of placental CRH increases during pregnancy.     

Spatial and developmental regulation of leptin in fetal sheep

To better understand the biology of leptin during prenatal life, the developmental and spatial regulation of leptin was studied in ovine fetuses. Fetal plasma leptin increased steadily between days 40 and 143 postcoitus (PC), but it was unrelated to fetal weight or placental weight at day 135 PC. Leptin gene expression was detected in fetal brain and liver during most of gestation and in fetal adipose tissue after day 100 PC. At day 130 PC, expression in fetal perirenal adipose tissue was approximately 10% of maternal expression. In contrast, leptin gene expression was never detected in the placenta and other uteroplacental tissues. When ewes were fed 55% of requirements between days 122 and 135 PC, fetal plasma leptin remained constant despite acute reduction in maternal concentration. We conclude that fetal plasma leptin originates mostly from nonadipose tissue in early pregnancy and, in addition, from fetal adipose tissue near term. The role of fetal plasma leptin remains uncertain given the lack of nutritional regulation and association with fetal growth.     

Fetal growth and placental diffusing capacity in guinea pigs following long-term maternal exercise

To determine the critical level of maternal exercise which produces effects on fetal weight and placental diffusing capacity, we measured the relationship between increasing levels of exercise and its effect on the fetus. Hartley guinea pigs with dated pregnancies were exercised on a treadmill (9.7 m/min at a 6.5% gradient) at one of five exercise levels (0, 15, 30, 45, and 60 min/day). We measured placental diffusing capacity for carbon monoxide (DPCO) fetal body and organ weights, placental weight, and maternal body and heart weights near term (63-64 days). Fetal body weight, kidney weight, and placental weight decreased as a function of increasing exercise level, decreasing 13, 13, and 21% respectively at 60 min/day exercise. DPCO1 decreased from a control value of 2.92 +/- 0.23 to 2.33 +/- 0.10 ml. min-1 torr-1 kg fetal wt in the 15 min/day exercise group, 2.17 +/- 0.08 in the 30 min/day group 2.16 +/- 0.11 in the 45 min/day group, and 2.65 +/- 0.31 in the 60 min/day exercise group. The decrease in placental weight along with the decrease in DPCO per kg of fetal weight suggests that with progressive maternal exercise the fetus is compromised by a smaller than normal placenta with less diffusing capacity.