Tissues Of Pregnant Rats Research Articles

Impact of oxidative stress on pregnancy outcome in albino rats

Accumulative reports documented that oxidative stress is implicated in many human and animal diseases. However, the reports concerning the effect of oxidative stress on pregnancy outcome are limited and scarce. The objective of this study was to determine the impact of oxidative stress on pregnancy outcome and to assess the antioxidant effect of vitamin C and E on oxidative stress parameters in blood and placental tissue samples in experimental pregnant animals model exposed to oxidative stress. Wister Albino rats were used in this work to investigate the effects of oxidative stress exposure (addition of H2O2 to the drinking water) on pregnancy outcome. Rats were divided into 5 groups, as follows: Group I (included 7 normal pregnant rats which served as control group). Group II (exposed to 1 % H2O2) included 7 pregnant rats, the rats were allowed to become pregnant and received (1% H2O2) in drinking water from day 7 th till the day 19 th of pregnancy. Group III (exposed to 3% H2O2) included 8 pregnant rats. Same as group 2, but the rats were exposed to a higher concentration of H2O2 (3%) in drinking water. Group IV (included 8 pregnant rats). Pregnant rats received vitamins C and E without induction of oxidative stress. Group V (included 8 pregnant rats).induction of oxidative stress by 1% H2O2 with vitamins supplementation in the pregnant rats. Serum total antioxidants capacity (TAC), serum and placental tissue oxidative stress biomarker; 8-iso prostaglandin F2α (8Isoprostane) were measured using specific ELISA kits. Also placental tissues of pregnant rats were isolated and put directly in 10% formalin prepared for histopathological examination. Results revealed a significant decrease in the median values of the body weight and total serum antioxidants capacity (TAC) in groups II and III of rats compared with the control group. A significant higher median value of TAC obtained in the groups IV and V when compared with the control group. Significant higher levels of serum and tissue Isoprostane observed in both groups II and III compared with control group. Histopathological, oxidative stress induced macroscopically degenerative with microscopical appearance of vasculitis and hemorrhage within decidua. Data of the present study demonstrated that imbalance oxidative stress status in pregnant rats occurred due to exposure to oxidant, which played an important role in the pathogenesis of abnormal pregnancy outcome. In addition antioxidants supplementation (vitamins E and C) were valuable in reducing this stress.

Influence of Maternal Diet During Early Pregnancy on the Fatty Acid Profile in the Fetus at Late Pregnancy in Rats

The aim of the study was to determine the effects of different dietary fatty acids during the first half of pregnancy on the fatty acid composition of maternal adipose tissue and of maternal and fetal plasma at mid- and late-pregnancy. Pregnant rats received soybean-, olive-, fish-, linseed- or palm-oil diets from conception to day 12 of gestation. Virgin rats receiving the same treatments were studied in parallel. At day 12, some rats were sacrificed and others were returned to the standard diet and studied at day 20. At day 12, the concentrations of most fatty acids in plasma reflected the dietary composition and individual fatty acids in lumbar adipose tissue of pregnant rats correlated with those in the diet. At day 20, the plasma concentration of each fatty acid was higher in pregnant than in both virgin rats and day-12 pregnant rats. The composition in 20-day pregnant (but not in virgin) rats resembled the diet consumed during the first 12 days. Fatty acid concentration in fetal plasma was also influenced by the maternal diet during the first 12 days of pregnancy, and long-chain polyunsaturated fatty acid (LC-PUFA) concentrations correlated with those in the mothers. In conclusion, during the first half of pregnancy maternal adipose tissue stores dietary-derived fatty acids, which are released into blood during late pregnancy enabling LC-PUFA to become available to the fetus.

The changes of Inducible Nitric Oxide Synthase, Endothelial Nitric Oxide Synthase and Cyclooxygenase-2 mRNA expressions in intrauterine tissues of pregnant rats

Prostaglandinler (PG) gebelikte rahim içi dokularda üretilirler ve doğum sırasındaki tüm fizyolojik süreçlerde önemli rol oynarlar. PG’ler araşidonik asitten siklooksijenaz (COX) enziminin aktivitesi ile sentezlenirler. Nitrik oksit (NO) güçlü bir düz kas gevşetici ve uterus kasılmasını baskılayan önemli bir bölgesel ara bulucu olarak kabul edilir. Nitrik oksit sentaz (NOS) ve COX ifadelenmesinin düzenlenmesinde NO ve PG yolakları arasında bir etkileşim olabilir ve bu etkileşim servikal olgunlaşma ve doğumun kontrolünde kritik bir rol oynayabilir. Bu çalışmanın amacı, hamile rat uterusunda gebelikte, doğum sırasında ve doğum sonrasında siklooksijenaz-2 (COX-2), uyarılabilir NOS (iNOS) ve endotelyal NOS (eNOS) mRNA düzeylerini incelemektir. Kırk iki hamile Sprague Dawley rat rastgele olarak 7 gruba ayrıldı. Her iki uterin boynuzu ve yavrular ve plasenta çıkarıldı. Tamamlayıcı DNA (cDNA) dokulardan total RNA izole edildikten sonra sentezlendi. iNOS, eNOS ve COX-2 genlerinin göreceli ifadelenmesi kantitatif gerçek zamanlı polimeraz zincir reaksiyonu (QRT-PCR) ile ölçüldü. iNOS mRNA düzeyleri gebelik sırasında arttı, doğum sırasında en yüksek düzeye çıktı ve doğum sonrasında azaldı. eNOS mRNA düzeyleri tüm gruplarda gebelik boyunca genel olarak düşüktü ve doğum sonrasında belirgin bir şekilde yükseldi. COX-2 mRNA düzeyleri gebeliğin sonlarına doğru azaldı, gebeliğin 21. gününde en yüksek seviyeye ulaştı ve doğum sonrası dönemde en düşük düzeylerde kaldı. Sonuç olarak servikal genişleme ve doğum sırasında, NO ve PG yolakları arasında bir etkileşim olabilir. Bu sonuçlar eNOS, iNOS ve COX-2 genlerinin mRNA düzeylerindeki değişikliklerin gebelikte servikal olgunlaşma ve doğum sırasında etkili olabileceğini gösterebilir

Nonclinical Pharmacokinetics of a New Nonpeptide V2 Receptor Antagonist, Tolvaptan

To evaluate the pharmacokinetic profile of tolvaptan. The nonclinical pharmacokinetic profile of [(14)C]tolvaptan was evaluated in an absorption, distribution, and excretion study in rats after single oral administration. An in vitro protein binding study was also performed. The tolvaptan-derived radioactivity was rapidly absorbed and extensively distributed to all tissues in rats. The radioactivity levels were greatest in the gastrointestinal tract and liver, though the levels in the cerebrum, cerebellum and medulla oblongata were low. The serum and tissue concentrations of radioactivity, and serum concentration of tolvaptan in male and female rats showed a marked sex difference. The radioactivity was crossed the placenta and was distributed to the fetal tissues in pregnant rats. The milk showed 1.5-15.8-fold higher radioactivity than blood in lactating rats. The radioactivity mainly excreted into the feces via the biliary route. Tolvaptan binds extensively to plasma proteins (≥ 97.2%) in mouse, rat, rabbit, dog and human plasma.

Expression of tumor necrosis factor in placenta tissue of pregnant rats with chronic peridontitis

To examine the expression of tumor necrosis factor in placenta of pregnant rats with chronic periodontitis. Twenty Wistar female rats were randomly divided into two groups, control (n = 8) and experimental group (n = 12). The periodontitis model was established in the experimental group. The females and males in the two groups got together four weeks later. Nineteen days after pregnancy all rats were executed and placenta collected. The delivery time and neonatal birth weight were recorded and the pathological changes of periodontal tissue observed. Tumor necrosis factor (TNF) expression was examined in placenta by real-time quantitative polymerase chain reaction analysis. The animal model of chronic periodontitis was successfully established. Experimental group delivered 30 offspring and the control group 56 offspring. The average number of pups born alive per litter in experimental group (4.1 ± 2.2) was significantly lower than that in control group (9.2 ± 2.2), P < 0.05. The birth weight of pups in experimental group [(5.01 ± 0.43) g] was significantly lower than that in the control group [(5.79 ± 0.53) g], P < 0.05. The relative quantitative expression of TNF was (1.807 ± 0.265) in experimental group the and (1.003 ± 0.021) in the control group (P = 0.001). Chronic periodontitis may be related to preterm low birth weight.

Impact of Polyinosinic/Polycytidylic Acid on Placental and Hepatobiliary Drug Transporters in Pregnant Rats

Although inflammation is known to impose changes in the expression and activity of drug transporters, little is known about the impact of inflammatory stimuli on these transporters during pregnancy. Our objective was to study the effect of viral-induced inflammation on key maternal hepatic and placental drug transporters and their endogenous substrates. Acute inflammation was induced in pregnant Sprague-Dawley rats (gestation day 17-18, n = 5-6/group) by single intraperitoneal doses of polyinosinic/polycytidylic acid [poly(I:C)] (2.5 or 5.0 mg/kg) with saline as a control. Tissues were harvested 24 h later. Expression of transporters was measured via real-time polymerase chain reaction and Western blotting. Maternal plasma levels of cytokines, bile acids, and bilirubin and fetal levels of bile acids were examined. Plasma concentrations of interferon-γ, tumor necrosis factor-α, and interleukin-6 were significantly induced in poly(I:C)-treated rats, compared with controls (p < 0.001). Significant down-regulation of placental Abcb1a/b, Abcc1, Abcc3, Abcg2, Slco1a4, and Slco4a1 mRNA and of hepatic Abcc2, Abcg2, Slco1a4, Slc10a1, and Cyp3a2 mRNA was observed in poly(I:C)-treated rats. Hepatic Abcb1b and Abcc3 mRNA levels were significantly induced. Hepatic protein levels of P-glycoprotein, multidrug resistance-associated protein 2, and breast cancer resistance protein were significantly down-regulated relative to those for controls (p < 0.05). Total bile acids in maternal plasma were significantly increased at the higher dose of poly(I:C). In summary, the poly(I:C) model of viral infection imposes significant changes in the expression of key drug transporters in placental and hepatic tissues of pregnant rats. Because many clinically important endogenous and exogenous compounds are substrates of these transporters, inflammation-mediated changes in transporter expression could affect their maternal disposition and fetal exposure.

Cadmium Intoxication of Pregnant Rats and Fetuses: Interactions of Copper Supplementation

Cadmium (Cd) is an industrial and environmental pollutant that was shown to be involved in the development of some diseases. Due to high amounts of Cd in cigarettes, smokers and passive smokers are exposed to high amount of Cd. We aimed to determine whether Copper (Cu) supplementation would have a protective effect against Cd intoxication in pregnant rats and their fetuses. Experiments were performed on 27 adult female Wistar albino rats divided into three experimental groups. CdCl(2), CdCl(2) plus CuSO(4) and only drinking water was given to different groups for 21 days. We measured cadmium (Cd), malondialdehyde (MDA), reduced glutathione (GSH), myeloperoxidase (MPO), superoxide dismutase (SOD) and catalase (CAT) levels in dams' liver, dams' kidney, fetus liver, fetus kidney, and placenta of rats. In all tissues of Cd and Cd + Cu-treated groups, Cd levels were found to be increased significantly when compared to control group. MDA levels and MPO activities were significantly increased whereas GSH levels, activities of SOD and CAT were decreased in Cd groups when compared to control group. Cu supplementation significantly prevented the increment in MDA levels and brought MPO activities back to control levels or below. Cd-induced reductions in GSH levels and SOD activities were also prevented by Cu supplementation. An increase of CAT activity after Cu supplementation was enough to revert to the control levels in some tissues. Our findings suggest that Cu supplementation may have a protective effect against the Cd-induced oxidative stress in liver, kidney and placental tissues of pregnant rats and fetuses.

Changes in antioxidant status and biochemical parameters after orally cadmium administration in females rats

The research was conducted to investigate the toxic effects of cadmium chloride (CdCl2), administered during gestation period on female Wistar rats. Pregnant rats received CdCl2 (20 mg/l, orally) from Day 6 to Day 19 of pregnancy. Results showed that Cd treatment induced a decrease in body weight gain. The relative liver weight increased significantly, with a marked decrease of glycogen and total lipids content. The administration of Cd induced hepatotoxicity as indicated by elevations in plasma alanine aminotransferase (ALT), aspartate aminotransferase and lactate dehydrogenase (LDH) activities (p < 0.05). Treatment with CdCl2 caused a significant (p < 0.05) increase in glucose. A significant increase was observed in the level of MDA and 8-oxodGuo tissues in the cadmium-exposed group compared to the control group (p < 0.05). Results showed that cadmium given to dams led to an oxidative stress and DNA damage in tissues of pregnant rats.

Effects of Malathion in Fetal Kidney Tissues in Pregnant Rats: Teratogenic Effects Induced by Different Doses

Effects of Malathion in Fetal Kidney Tissues in Pregnant Rats: Teratogenic Effects Induced by Different Doses

Morphological, Biochemical and Ultrastructural Changes in the Pregnant Rat Placenta and the Liver of their Fetuses Treated with Folic Acid and / or Gamma Radiation

Backgrounds: The efficacy of antioxidant supplementation and oxidative stress of gamma irradiation for and during pregnancy is poorly established. The present study aimed to detect the toxic effects of high dose of folic acid and / or gamma radiation on the placenta of pregnant rat and the liver of their fetuses. Material and Methods: Pregnant albino rats were divided into four groups. The first group served as a control, the second group received oral intake of folic acid (5 mg/kg) from the 5th to 20th day of gestation, the third group was irradiated with gamma radiation (3Gy, as fractionated doses (1Gy/ 3 times) on each 5th, 10th and 15th days of gestation, the fourth group was imanaged with combined treatment. The pregnant rats were sacrified after 20 days of pregnancy and samples were taken from the blood, placenta and the fetal liver for the morphological, biochemical and electron microscopic studies. Results: The present results showed a significant elevation in serum gamma glutamyltransferase (GT), lactate dehydrogenase (LDH) in placental tissue of pregnant rats associated with an increase of phosphorus content in liver of fetuses. Fetal malformations including: protrusion, anotia, short neck dactylomegaly, subcutaneous haemorrhage, paralysis in the fore limbs and congested blood vessels. The ultrastructural changes revealed sever damage in the placenta following folic acid administration and / or exposure to whole body gamma radiation. Also the fetal liver showed an appearent signs of damage under the combined treatment. The obtained changes were represented by: dilatation of the blood sinsoids, swollen mitochondria, fragmented rough endoplasmic reticulum and necrosis. Conclusion: It could be concluded that administration of folic acid and/or exposure to gamma radiation during pregnancy induced morphological, biochemical and ultrastructural changes in both placenta of the pregnant rats and liver of their fetuses.

Morphological, Biochemical and Ultrastructural Changes in the Pregnant Rat Placenta and the Liver of their Fetuses Treated with Folic Acid and / or Gamma Radiation

Backgrounds: The efficacy of antioxidant supplementation and oxidative stress of gamma irradiation for and during pregnancy is poorly established. The present study aimed to detect the toxic effects of high dose of folic acid and / or gamma radiation on the placenta of pregnant rat and the liver of their fetuses. Material and Methods: Pregnant albino rats were divided into four groups. The first group served as a control, the second group received oral intake of folic acid (5 mg/kg) from the 5th to 20th day of gestation, the third group was irradiated with gamma radiation (3Gy, as fractionated doses (1Gy/ 3 times) on each 5th, 10th and 15th days of gestation, the fourth group was imanaged with combined treatment. The pregnant rats were sacrified after 20 days of pregnancy and samples were taken from the blood, placenta and the fetal liver for the morphological, biochemical and electron microscopic studies. Results: The present results showed a significant elevation in serum gamma glutamyltransferase (GT), lactate dehydrogenase (LDH) in placental tissue of pregnant rats associated with an increase of phosphorus content in liver of fetuses. Fetal malformations including: protrusion, anotia, short neck dactylomegaly, subcutaneous haemorrhage, paralysis in the fore limbs and congested blood vessels. The ultrastructural changes revealed sever damage in the placenta following folic acid administration and / or exposure to whole body gamma radiation. Also the fetal liver showed an appearent signs of damage under the combined treatment. The obtained changes were represented by: dilatation of the blood sinsoids, swollen mitochondria, fragmented rough endoplasmic reticulum and necrosis. Conclusion: It could be concluded that administration of folic acid and/or exposure to gamma radiation during pregnancy induced morphological, biochemical and ultrastructural changes in both placenta of the pregnant rats and liver of their fetuses.

Melatonin Concentration in Plasma, Pineal Gland and Duodenum of Pregnant Rats and their Fetuses after Melatonin and Phenytoin Administration

Melatonin (MEL) is involved in regulation of variety of physiological processes. Beside the pineal gland, the presence of MEL was confirmed in the gastrointestinal tract (GIT), where it may exert multiple actions. We investigated the effects of a single MEL administration of 0.4, 4.0 and 40.0 μg MEL/ml of tap water on MEL levels in rat plasma, pineal gland and duodenum. In addition, we studied the effect of a prolonged administration of MEL, an anticonvulsant drug phenytoin (PHT) and a combination of MEL+PHT, on MEL concentrations in pregnant rats and their fetuses. Single MEL administration of 4.0 and 40.0 μg MEL/ml resulted in a dose-related increase of MEL concentration in the rat plasma and duodenum but in a decrease of MEL in the pineal gland. After a prolonged MEL administration, MEL levels in duodenal tissues were significantly lower in control group and group treated with PHT as compared to animals, where MEL and PHT were administered simultaneously. A significant increase in MEL concentration was recorded in the intestine of fetuses taken from mothers treated with MEL and MEL + PHT. Our results indicate a dose-related absorption of MEL from tap water to GIT tissues of pregnant rats and their fetuses, where MEL may increase the protection of the intestinal mucose.

Development of a Physiologically Based Pharmacokinetic Model of 2-Methoxyethanol and 2-Methoxyacetic Acid Disposition in Pregnant Rats

An accurate description of developing embryos' exposure to a xenobiotic is a desirable component of mechanism-based risk assessments for humans exposed to potential developmental toxicants during pregnancy. 2-Methoxyethanol (2-ME), a solvent used in the manufacture of semiconductors, is embryotoxic and teratogenic in all species tested including nonhuman primates. 2-Methoxyacetic acid (2-MAA) is the primary metabolite of 2-ME and the proximate embryotoxic agent. The objective of the work described here was to adapt an existing physiologically based pharmacokinetic (PBPK) model for 2-ME and 2-MAA kinetics during midorganogenesis in mice to rats on gestation days (GD) 13 and 15. Blood and tissue data were analyzed using the extrapolated PBPK model that was modified to simulate 2-ME and 2-MAA kinetics in maternal plasma and total embryo tissues in pregnant rats. The original mouse model was simplified by combining the embryos and placenta with the richly perfused tissue compartment. The model includes a description of the growth of the developing embryo and changes in the physiology of the dam during pregnancy. Biotransformation pathways of 2-ME to either ethylene glycol (EG) or to 2-MAA were described as first-order processes based on the data collected from rats by Green et al., (Occup. Hyg. 2, 67–75, 1996). Tissue partition coefficients (PCs) for 2-ME and 2-MAA were determined for a variety of maternal tissues and the embryos. Model simulations closely reflected the biological measurement of 2-ME and 2-MAA concentrations in blood and embryo tissue following gavage or iv administration of 2-ME or 2-MAA. The PBPK model for rats as described here is well suited for extrapolation to pregnant women and for assessment of 2-MAA dosimetry under various conditions of possible human exposure to 2-ME.

Adrenomedullin attenuates the hypertension in hypertensive pregnant rats induced by NG-nitro- l-arginine methyl ester

We examined the effect of adrenomedullin on the cardiovascular system of an animal model for preeclampsia. An inhibitor of nitric oxide synthase, N G-nitro- l-arginine methyl ester ( l-NAME), was infused subcutaneously into rats at a constant rate from day 14 of pregnancy to make an animal model for preeclampsia. Adrenomedullin was continuously infused intravenously at a dose of 3 or 10 pmol/h from day 17 of pregnancy. The basal systolic blood pressure was significantly higher in the l-NAME treated rats than in the control rats. The adrenomedullin administration at day 19 of pregnancy showed a significant decrease in the blood pressure in the l-NAME treated rats than in vehicle rats during infusion. The blood pressure of normal pregnant rats did not significantly decrease by adrenomedullin infusion. The adrenomedullin decreased pup mortality of the l-NAME treated rats. Adrenomedullin attenuated the l-NAME induced hypertension and pup mortality. On the other hand, adrenomedullin administration in both pregnant rats in early gestation (5–11 days of pregnancy) and in non-pregnant rats did not show any significant effect on l-NAME-induced hypertension. The adrenomedullin mRNA level was predominantly expressed at high levels in the ovary, uterus and placenta, but at low levels in other tissues in pregnant rats in late gestation. The adrenomedullin mRNA level of the l-NAME treated rats in placenta decreased more than in the normal pregnant rats in late gestation ( P<0.05). These findings suggest that the adrenomedullin might play an important role in the regulation of the cardiovascular system of the mother and fetoplacental unit in rats.

Alpha-Tocopherol Concentration in Fetal and Maternal Tissues of Pregnant Rats Supplemented with Alpha-Tocopherol

We wanted to determine whether alpha-tocopherol supplementation to pregnant rats could increase the concentration of alpha-tocopherol in maternal and fetal plasma and tissues. Pregnant rats were treated with alpha-tocopherol on days 18 and 19 gestation and studied at day 20. A control group was studied in parallel. Treatment of pregnant rats with alpha-tocopherol increased its concentration in maternal and fetal plasma, in all maternal plasma lipoprotein fractions, in maternal and fetal liver and in the placenta. The fetal and maternal concentration of alpha-tocopherol were positively correlated.

Hexokinase II activity and messenger ribonucleic acid abundance in adipose tissue and skeletal muscle during pregnancy and lactation in rats

OBJECTIVE: Our purpose was to investigate the influence of pregnancy and lactation on hexokinase II activity and gene expression in adipose tissue and skeletal muscle of rats. STUDY DESIGN: Intraabdominal adipose tissue and femoral quadriceps muscle were removed from Sprague-Dawley rats at various times (6 to 10 animals per group) during pregnancy and lactation. Hexokinase II messenger ribonucleic acid was assayed by quantitative ribonuclease protection analysis, and hexokinase activity was measured with the glucose-6-phosphate–coupled assay. RESULTS: The amount of hexokinase II messenger ribonucleic acid in adipose tissue on day 20 of pregnancy was 55.4% ± 8.4% ( p < 0.01, unpaired Student t test) of the value for nonpregnant control rats; hexokinase II activity was also decreased in this tissue at this time (39.34 ± 3.05 vs 27.81 ± 3.61 mU · min –1 · mg protein –1, p < 0.05). Hexokinase II activity and messenger ribonucleic acid abundance in skeletal muscle were unaffected by pregnancy and lactation. CONCLUSION: Both hexokinase II messenger ribonucleic acid abundance and enzyme activity are reduced in adipose tissue of pregnant rats near term, possibly contributing to the insulin resistance associated with late pregnancy.(Am J Obstet Gynecol 1997;176:651-5.)

Differential expressions of collagen types IV, III, and I during the development of invasive trophoblasts in rats.

We examined the differential expressions of collagen types IV, III and I in the developing feto-maternal placental tissue of pregnant rats by a combination of in situ hybridization and immunohistochemistry. At day 9.5 of gestation, polygonal invasive cytotrophoblasts from the ectoplacental cone, which was modifying the maternal central artery, revealed intensely expressed alpha 1 (IV) and alpha 1 (III) collagen mRNAs. The localization patterns of these translated products, collagen type IV and procollagen type III, were slightly different in the invasive cytotrophoblasts. Collagen type IV densely deposited intracellularly and intercellularly in the maternal central artery and in the thickened basement membranes of the cytotrophoblasts. However, expression of alpha 1 (I) collagen mRnA and procollagen type I was hardly detectable in the cytotrophoblasts. At day 13 of gestation, a high level of alpha 1 (IV) collagen mRNA was expressed in the cytotrophoblastic cell layer (trophospongium) and in the invasive large cytotrophoblasts. A moderate level of alpha 1 (III) collagen mRNA was also expressed mainly in the cytotrophoblasts, while alpha 1 (I) collagen mRNA was expressed at very low levels. Interestingly, procollagen type III failed to show linear immunoreactivity in the subepithelial extracellular matrix beneath the maternal artery with the invasive cytotrophoblasts. Additional quantitative analyses of these type IV, III, and I collagen mRNA levels in in situ hybridization experiments between several cell types also revealed significant differences individually. Electron-microscopic study detected no cross-striated collagen fibers in the thickened basement membrane-like structures adjacent to the invasive cytotrophoblasts. Fibrillar and basement membrane collagen gene expressions, their protein syntheses, and the processing of these procollagens seems to be developmentally regulated in the invasive cytotrophoblasts during the organization of feto-maternal placental tissue. The remodeling of the maternal central artery by the invasive cytotrophoblasts is important for ensuring the adequate blood supply to the developing placenta and fetus.

Differential expressions of collagen types IV, III, and I during the development of invasive trophoblasts in rats

We examined the differential expressions of collagen types IV, III, and I in the developing feto-maternal placental tissue of pregnant rats by a combination of in situ hybridization and immunohistochemistry. At day 9.5 of gestation, polygonal invasive cytotrophoblasts from the ectoplacental cone, which was modifying the maternal central artery, revealed intensely expressed α1(IV) and α1(III) collagen mRNAs. The localization patterns of these translated products, collagen type IV and procollagen type III, were slightly different in the invasive cytotrophoblasts. Collagen type IV densely deposited intracellularly and intercellularly in the maternal central artery and in the thickened basement membranes of the cytotrophoblasts. However, expression of α1(I) collagen mRNA and procollagen type I was hardly detectable in the cytotrophoblasts. At day 13 of gestation, a high level of α1(IV) collagen mRNA was expressed in the cytotrophoblastic cell layer (trophospongium) and in the invasive large cytotrophoblasts. A moderate level of α1(III) collagen mRNA was also expressed mainly in the cytotrophoblasts, while α1(I) collagen mRNA was expressed at very low levels. Interestingly, procollagen type III failed to show linear immunoreactivity in the subepithelial extracellular matrix beneath the maternal artery with the invasive cytotrophoblasts. Additional quantitative analyses of these type IV, III, and I collagen mRNA levels in in situ hybridization experiments between several cell types also revealed significant differences individually. Electron microscopic study detected no cross-striated collagen fibers in the thickened basement membrane-like structures adjacent to the invasive cytotrophoblasts. Fibrillar and basement membrane collagen gene expressions, their protein syntheses, and the processing of these procollagens seem to be developmentally regulated in the invasive cytotrophoblasts during the organization of feto-maternal placental tissue. The remodeling of the maternal central artery by the invasive cytotrophoblasts is important for ensuring the adequate blood supply to the developing placenta and fetus. © 1996 Wiley-Liss, Inc.

Ethanol inhibits cadmium accumulation in brains of offspring of pregnant rats that consume cadmium

The present study was designed to test the effect of ethanol on cadmium accumulation in tissues of pregnant rats and their offspring. Starting 10 days before mating and continuing until parturition, ethanol (10% v/v) was present in the drinking water of half the rats. Cadmium chloride (CdCl 2; 50 ppm) was present in the water of half the rats (± ethanol) from the first day after mating until parturition. On the day of parturition cadmium accumulated to a moderate level in bone (7.3 μg/g tissue, wet weight; this and other values, P < 0.05 vs. control), liver (12.9 μg/g) and kidney (13.0 μg/g) of dams, while the brain had only a low level of cadmium (0.45 μg/g). In offspring at 6 weeks cadmium accumulated in high amounts in the brain (34.0 μg/g), bone (15.9 μg), kidney (78.2 μg/g) and particularly the liver (227.3 μg/g). Ethanol, given simultaneously with cadmium, inhibited cadmium accumulation in brain (1.8 μg/g), bone (3.28 μg/g) and kidney (61.3 μg/g), but enhanced cadmium accumulation in liver (408.7 μg/g). At 12 weeks there were only residual levels of cadmium in all tissues of offspring. These findings demonstrate an interaction between 2 known teratogenic agents, with ethanol conferring protection of the brain from cadmium accumulation. The nature of this interaction is not known, but is likely to be related to ethanol induction of metallothionein in the liver and placenta.

Mineral interactions in rats fed AIN-76A diets with excess calcium

The effects of moderate increases in dietary calcium on maternal and foetal mineral interactions were studied in Charles River CD/VAF Plus rats. Female rats were given 0.50, 0.75, 1.00 or 1.25% dietary calcium as calcium carbonate in AIN-76A diets for 6 wk before mating, during mating and for 20 days of gestation. Inductively coupled argon plasma-atomic emission spectrometry was used to determine mineral levels in the tissues of non-pregnant rats after 42 days on the diets, in the tissues of pregnant rats on day 20 of gestation and in the whole body of day-20 foetuses. The femurs of the non-pregnant and pregnant rats had a dose-related linear increase in calcium content. In livers of the non-pregnant rats, dose-related linear increases in the phosphorus, zinc and magnesium content were observed, but there was a dose-related decrease in the iron content. There were dose-related linear decreases in the iron and copper contents of the kidneys from the non-pregnant rats. In pregnant rats dose-related linear decreases were observed in the iron content of the liver and in the zinc, iron and magnesium contents of the kidney. The foetuses from rats given a moderate increase in dietary calcium had dose-related decreases in the whole-body contents of phosphorus, iron, copper and magnesium.