Radium - 226 retention in placenta and whole body of rat

The 226Ra retention in the placenta of rat during 3 successive pregnancies (92-213 days after injection) was about 4-5 x 10(-3)% of the injected dose (ID) constituting nearly 0.009% of the whole body 226Ra content (45-55% ID) in each pregnancy. Thus a uniform relationship was being displayed between the two contents to a reasonable extent. The implication of this observation is discussed vis-a-vis the determination of Ra body burden.     

Vertical transmission and pathological findings in the mother,the placenta and the offspring,during first and last thirds of gestation in a mouse model of congenital toxoplasmosis

We performed a study of congenital toxoplasmosis of the first and third gestation periods in mice, and determined its effects on the embryos/fetuses, the placentae and the maternal organs. We infected pregnant BALB/c mice by i.v. injection of 2.5‐–10.0 × 10⁶ tachyzoites of the ME49 T. gondii strain and euthanized them 72 h later. The tissues were analyzed by histopathology, immunohistochemistry and parasite-specific qPCR. Infections with the lowest dose induced remarkably different changes in the two thirds: a) all doses diminished the number of products/litter, the lowest dose only by 14%; but most embryos still visible were degenerated in the case of the first period, while the fetuses of the last third were perfectly preserved; b) the transmission rate in the first third was relatively high, but with a very low parasite burden; c) with the lowest dose, strong vascular changes (congestion, thrombosis and hemorrhage) predominated in the placentas of the first period, while they were absent in the last third; d) necrosis caused by T. gondii to maternal organs was much stronger during the last gestation period than in the first. Our results suggest that the vascular alterations at the placenta of the first third of pregnancy prevent embryo from large parasite burden, but provoke its death by starvation. In the last gestation period, there was poor control of parasite dissemination to the placenta and the fetus, but there was greater capacity of the product to defend itself from T. gondii.     

Study of trans-placental transport of methylamphotericin B in albino rats after intravenous administration]

Transplacental penetration of amphotericin B, an methyl derivative, was studied on rats after its intravenous administration. Microbiological and radioisotopic methods were used. When the microbiological method was applied the drug was administered on days 16 to 20 or on day 20 of pregnancy in a dose of 4 mg/kg. For extraction of the antibiotic dimethylformamide was added to the substrates. The labeled antibiotic was administered in a dose of 3.3 mg/kg on days 6 to 16 and on day 20 of pregnancy. It was noted that the antibiotic accumulated in the placenta. The accumulation was more pronounced after antibiotic use in the course doses. A significant part of the antibiotic was in the placenta in the bound state. The methyl derivative amphotericin B was not detected microbiologically in the umbilical cord serum, fetal organs and amniotic fluid. Neither was it detected by extraction with ++dimethylformamide. The labeled antibiotic was neither detected in the amniotic fluid and fetal organs during the whole observation period. Therefore, the methyl derivative amphotericin B did not penetrate through the placental barrier either in the free or bound state. The direct teratogenic action of amphotericin B, a methyl derivative, after its intravenous administration to female rats is likely possible.     

Penetration of beryllium through the placenta and its distribution in the mouse

Penetration of beryllium through the placenta and its distribution in the organs after intravenous administration of BeCl2 in a dose of 0.1 mg/kg was studied in a series of experiments on ICR SPF mice. To trace the fate of beryllium, an isotope in the form of 7BeCl2 in an amount of 111kBq per animal was used. This dose was administered to a group of females before fertilization, on the 7th and 14th day of pregnancy, and to control animals. The animals were killed on the 18th to 19th day of pregnancy and the content of beryllium in the foetuses and its distribution in the organs of the mothers were determined by measuring activity. It has been found that beryllium penetrates through the placenta with difficulty, however, part of the dose administered circulated in the blood long enough for Be to penetrate the foetuses. Of interest is the finding that beryllium in the dose administered influenced the number of foetuses of the exposed females. This finding deserves detailed evaluation in the test of dominant lethal mutations.     

Progesterone and the initiation of parturition in the goat

The corpora lutea were surgically removed from 6 goats between 134 and 136 days of pregnancy and progesterone was administered daily. Pregnancy was prolonged past normal term in 4 goats receiving 25 mgs. of progesterone daily as a split dose. However, eventual delivery following progesterone withdrawal was abnormal and foetal mortality high.The progesterone therapy regime maintained maternal jugular plasma concentrations of progesterone in excess of 3 ng/ml. In normal untreated goats, maternal plasma concentrations of progesterone declined over the last 6 days of gestation. In treated goats, plasma concentrations of progesterone fell only after the cessation of therapy. Maternal plasma concentrations of estrogen rose within 24 hours of parturition in normal untreated goats. In the 4 goats in which pregnancy was prolonged, by progesterone administration, maternal plasma concentrations of estrogen were elevated for several days in the period before eventual foetal delivery.     

Excretion of fetal biliverdin by the rat placenta-maternal liver tandem

Fetal liver immaturity is accompanied by active heme catabolism. Thus fetal biliary pigments must be excreted toward the mother by the placenta. To investigate biliverdin handling by the placenta-maternal liver tandem, biliverdin-IXalpha was administered to 21-day pregnant rats through the jugular vein or the umbilical artery of an in situ perfused placenta. Jugular administration resulted in the secretion into maternal bile of both bilirubin and biliverdin (3:1). However, when biliverdin was administered to the placenta, most of it was transformed into bilirubin before being transferred to the maternal blood. Injecting Xenopus laevis oocytes with mRNA from rat liver or placenta enhanced their ability to take up biliverdin, which was inhibited by estradiol 17beta-d-glucuronide. The expression of three OATP isoforms in this system revealed that they have a varying degrees of ability to transport biliverdin (Oatp1/1a1 > Oatp2/1a4 > Oatp4/1b2). The abundance of their mRNA in rat trophoblast was Oatp1/1a1 > Oatp4/1b2 > Oatp2/1a4. The expression of biliverdin-IXalpha reductase in rat placenta was detected by RT-PCR/sequencing and Western blot analysis. The relative abundance of biliverdin-IXalpha reductase mRNA (determined by real-time quantitative RT-PCR) was fetal liver > placenta > maternal liver. Common bile duct ligation in the last week of pregnancy induced an upregulation of biliverdin-IXalpha reductase in maternal liver but had no effect on fetal liver and placenta. In conclusion, several members of the OATP family may contribute to the uptake of fetal biliverdin by the rat placenta. Before being transferred to the mother, biliverdin is extensively converted into bilirubin by biliverdin-IXalpha reductase, whose expression is maintained even though bilirubin excretion into maternal bile is impaired.     

Relationship of physiological factors to placental retention in dairy cattle

Various physiological and environmental factors were examined for possible association with retention of the fetal membranes in a herd experiencing a high incidence of this problem. Data were collected on 116 multiparous and primiparous cows during the first lactation of the trial and 57 multiparous cows during the second lactation of the trial. No mineral or heavy metal deficiencies or toxicities were detected in the herd and injections of selenium and/or vitamins A, D and E during the prepartum period were not beneficial. Also, no common disease entity could be found in this herd. Placental retention rates observed were 28% and 42% in the first and second lactations, respectively, of this study. The incidence of retained placenta was higher in cows giving birth to twins or male calves, and following abortions, stillbirths or placental retention at the previous parturition. Seasonal effects varied, with a higher retention rate in the warm season in the first lactation and in the cold season in the second lactation. Factors examined that did not show a statistically significant relationship to the placental retention rate included: blood serum vitamin A and β-carotene concentrations; age or lactation number; calf birth weight; presence of serum antibodies to leucosis or chlamydia; incidence of milk fever or ketosis; and services per conception, days open and gestation length of the pregnancy prior to retention. Cows with retained placenta subsequently had longer postpartum intervals to first ovulation and more uterine infections, foot problems and mastitis than cows without retained placenta.     

Enzyme activities in the sheep placenta during the last three months of pregnancy

In order to assess the extent to which metabolism within the sheep placenta may influence the transfer of metabolites between mother and foetus at different stages of gestation the activities of enzymes concerned with some aspects of carbohydrate, amino acid and ketone body metabolism were determined in placental cotyledons resected from ewes during the last three months of pregnancy.The activities of pyruvate kinase (EC 2.7.1.40), lactate dehydrogenase (EC 1.1.1.27), malate dehydrogenase (EC 1.1.1.37), ATP citrate (pro-3S)-lyase (EC 4.1.3.8), citrate (si)-synthase (EC 4.1.3.7), acetyl-Co A synthetase (EC 6.2.1.1), acetyl-CoA acetyltransferase (EC 2.3.1.9) and 3-keto acid CoA-transferase (EC 2.8.3.5) per gram wet weight cotyledon do not change during the period studied. The activities of alanine aminotransferase (EC 2.6.1.2), aspartate aminotransferase (EC 2.6.1.1), isocitrate dehydrogenase (NADP⁺) (EC 1.1.1.42), ornithine-oxoacid aminotransferase (EC 2.6.1.13) and 3-hydroxybutyrate dehydrogenase (EC 1.1.1.30) show an increase in activity between the third and fourth months of pregnancy whilst the activities of arginase (EC 3.5.3.1) and possibly pyruvate carboxylase (EC 6.4.1.1) show an increase in activity between the fourth and final months of pregnancy. Ornithine decarboxylase (EC 4.1.1.17) activity declines to one tenth of its activity during this later period. The absence of detectable activities of phosphoenolpyruvate carboxykinase (EC 4.1.1.32) and ornithine carbamoyltransferase (EC 2.1.3.3) indicate that gluconeogenesis and urea synthesis from ammonia do no occur in the sheep placenta.It appears that the ability of the placenta to metabolise several substrates is achieved by the time the placenta reaches its maximum size at approximately 90 days.     

Two-drug combinations of memory enhancers: effect of dose ratio upon potency and therapeutic window, in mice

Two-drug combinations have been reported to enhance retention more effectively than when either drug was administered alone at the same dose. Some combinations of cholinergic drugs enhance retention even though the total drug dosage is reduced by as much as 97% compared to the dose needed to improve retention when the same drugs are administered singly. The choice of dose ratio is usually arbitrary or based on empirical results. The present study systematically varied the ratio of two drugs in a combination and at the same time varied the dosage of each drug. The drug combinations were administered to mice immediately after training on T-maze footshock avoidance task. Retention was tested one week later. Three two-drug combinations were selected for presentation because they differed considerably as to (a) the lowest effective total dose that improved memory-retention, (b) the optimal ratio that improved retention and (c) the width of the therapeutic window. The effect of a drug combination on retention was found to be dependent on the particular drugs in the combination, the ratio and the dose administered.     

Influence of the oral administration of micronized progesterone on plasma and tissue levels of steroids in human pregnancy

A single dose of micronized progesterone, orally administered to women at different stages of pregnancy, induced an immediate increase in the plasma levels of progesterone. Progesterone was administered to another group of women just before elective cesarean section. Levels of progesterone, oestradiol-17 beta and oestrone were determined in plasma, placenta and at different sites of the myometrium obtained during the surgical procedure. Results were compared to those observed in a control group of women who did not receive progesterone. Progesterone levels demonstrated a marked increase in plasma and in the whole myometrium 150 min after administration; the levels then decreased rapidly to control values within one hour. The concentrations of progesterone in the placenta did not show any change. Evident modifications of the oestrogen levels appeared in the myometrium and in the placenta after the administration of progesterone whereas no change occurred in the plasma. No difference was observed in estradiol-17 beta in the myometrium whereas an increase was seen in the placenta. Estrone levels decreased in the myometrium and in the placenta. This study demonstrates a prompt delivery of an orally administered natural progesterone to the myometrial target tissue and subsequent modifications in the estrogen pattern. This provides a theoretical mechanism for the clinical use of progesterone in the prevention of premature labor.     

Serum and placenta levels of ethynylestradiol in presence of ethynodiol diacetate after oral administration

The ethynylestradiol concentration--in the presence of ethynodiol diacetate--in serum after oral administration was measured by a rapid radioimmunoassay method developed by the authors. It was found that the peak level was reached 1 h after administration, and even after 12 h a significant amount of free ethynylestradiol was present in the serum. The transfer of ethynylestradiol into the placenta was also studied in subjects who were 10-12 weeks pregnant. Placenta/serum quotients were calculated for the ethynylestradiol, and were found to increase in parallel with the dose of the drug administered, proving that an ethynylestradiol enrichment of the placenta occurred as early as 10-12 weeks of pregnancy.     

Effect of xylazine,isoxsuprine, and lidocaine on Doppler sonographic uterine and umbilical blood flow measurements in cows during the last month of pregnancy

The maternal portion of the bovine placenta receives blood mainly from the uterine arteries (AUT) and the fetal portion from the umbilical arteries (AUM). Placental perfusion is crucial for fetal development and undergoes adaptive changes during pregnancy according to the fetal requirements. One goal of this study was to investigate changes in Doppler sonographic measurements of blood vessels that supply blood to the placenta in cows during the last 4 weeks of pregnancy. Another goal was to examine how these measurements are affected by three drugs commonly used in cows at the time of parturition. Nine cows underwent Doppler sonographic examination of the AUT ipsilateral and contralateral to the pregnant horn and one AUM three times per week during the last 4 weeks of gestation. This was followed by the randomized administration of one of the three following experimental drugs per day: isoxsuprine (200 mg/cow, iv), xylazine (2 mg/100 kg, iv), and lidocaine for epidural anesthesia (100 mg/cow). Doppler sonographic examination was repeated 30 minutes after medication. Maternal pulse rate increased during the study period (P < 0.001), and the diameter of the contralateral AUT was smaller in the last week before birth than in the two preceding weeks. The resistance index (RI) of the ipsilateral AUT was smaller in the last week than in the first 2 weeks of the study period. Uterine blood flow volume increased after isoxsuprine by 5% and after epidural anesthesia by 6% (both P ≤ 0.05) and decreased after xylazine by 10% (P < 0.001). Isoxsuprine was the only drug that elevated the blood flow volume in the AUM (P ≤ 0.05). Xylazine increased the RI of both AUT (both P < 0.001) and significantly reduced maternal and fetal pulse frequencies, whereas isoxsuprine significantly reduced the RI of both AUT and the AUM and increased maternal and fetal pulse frequencies. The results reported that Doppler sonographic measurements of uterine and AUM change little in the last month of pregnancy in the cow. Isoxsuprine and epidural anesthesia with lidocaine have the potential to improve uterine perfusion.     

Effect of sex hormone on the respiration and glycolysis processes in female rabbit placenta tissue

The respiratory and glycolytic activity of the female-rabbits placenta tissue on the 11th and 30th days of pregnancy was studied as affected by progesterone, estrone and chorionic gonadotrophin. The tissue respiration of the placenta at the end of pregnancy is established to be more sensitive to administration of the hormones under study than at the beginning of pregnancy. The glycolytic activity of the placenta tissue under the effect of hormones is decreased both at the beginning and at the end of pregnancy. Only anaerobic glycolysis is an exception when progesterone is administered at the beginning of pregnancy.     

Factors affecting the fertility of high producing dairy herds in northeastern Spain

Infertility has been often correlated to a rising milk yield in high producing dairy cattle. The aim of the present study was to evaluate, using logistic regression procedures, the effects of several management indicators on the fertility of four dairy herds in northeastern Spain. Data derived from 10,965 artificial insemination (AI). The factors examined were: herd, milking frequency (three versus two milkings per day), lactation number, previous twinning and disorders such as placenta retention and pyometra, milk production at AI, the inseminating bull, season (warm versus cool period) and year effects, AI technician and repeat breeding syndrome (cows undergoing four or more AI). Our findings indicated no effects on fertility of the herd, year of AI, previous twining, placenta retention and pyometra and milk production at AI. Based on the odds ratios, the likelihood of pregnancy decreased: in cows milked three times per day (by a factor of 0.62); for each one unit increase in lactation number (by a factor of 0.92); for inseminations performed during the warm period (by a factor of 0.67); in repeat breeder cows (by a factor of 0.73); and when 3 of the 45 inseminating bulls included in the study were used (by factors of 0.35, 0.43 and 0.44, respectively). Of the 13 AI technicians participating in the study, 3 were related to a fertility rate improved by odds ratios of 1.86, 1.84 and 1.30, respectively, whereas 2 technicians gave rise to fertility rates reduced by odds ratios of 0.64 and 0.49, respectively. Under our study conditions, management practices were able to compensate for the effects of previous twining and reproductive disorders such as placenta retention and pyometra. However, fertility was significantly affected by the factors milking frequency, AI technician, inseminating bull, repeat breeding syndrome, lactation number and AI season.     

TRPV5 and TRPV6 are expressed in placenta and bone tissues during pregnancy in mice

We investigated the dynamic expression of calcium transporters, TRPV5 and TRPV6, in placenta and bone to determine their role in maternal and fetal calcium balance during gestation. In placenta, TRPV5 was expressed predominantly in syncytiotrophoblasts of the labyrinthine zone, whereas TRPV6 was expressed in spongiotrophoblasts of the junction zone. In bone, the two transporters were found in osteoblasts, osteoclasts, cartilage and bone matrices. During the first half of gestation, TRPV5 and TRPV6 levels in bone were increased on pregnancy day (P) 0.5, then decreased on P3.5 followed by a slight increase on P6.5. During the second half of pregnancy, both the proteins and their mRNAs gradually increased from P9.5 to P15.5?P17.5 in both bone and placenta, followed at parturition by relatively high amounts in placenta, but markedly decreased amounts in bone. The expression pattern is likely related to the fetal and maternal calcium requirement during gestation, which may be regulated by estrogen and other hormones, because the fetal demand for calcium is greatest during the last few days of gestation for rats; maternal calcium metabolism is designed to meet the calcium needs of the fetus during this period. We found that TRPV5 and TRPV6 are involved in calcium transport in the placenta and bone, and therefore play a role in calcium homeostasis during embryonic and fetal development.     

Efficacy of Ginkgo biloba on Vaginal Estrous and Ovarian Histological Alterations for Evaluating Anti‐Implantation and Abortifacient Potentials in Albino Female Mice

Ginkgo extract, EGb 761 is known as a vasoregulatory variable for the conventional reproduction therapy. EGb 761 was orally administered in 0 (control), 3.7, 7.4, and 14.8 mg/kg bw/day for 28 days (thereafter mated with normal fertile male), from day 1 to day 7 of pregnancy or from the 10th to 18th day of pregnancy, respectively. Vaginal smears were performed daily. On 20th day of pregnancy, the females were killed by cervical dislocation and their kidneys, liver, brain, placenta, spleen and ovaries were removed and weighed. The ovaries were prepared for histological examinations, and then ovarian follicles were counted. Maternal toxicity, estrous cycle, reproductive hormones, ovarian follicle counts, resorption index, implantation index, fetal viability and fetuses, and placenta mean weights were evaluated. There was a dose‐dependent ovarian toxic effect of EGb 761. Ovarian follicle counts, resorption index, implantation index, fetal viability were significantly reduced in 14.8 mg/kg bw/day dose. Treatment with 14.8 mg/kg bw/day EGb 761 induced disruption of estrous cycle and caused maternal toxicity, in addition to fetal toxicity. Therefore, the data obtained indicate that Ginkgo biloba extract at 14.8 mg/kg bw/day dose level exhibit toxic effect on reproductive cyclicity and could have anti‐implantation and abotifacient properties in female mice.     

Effect of gavaged chemical form of 241Am on its retention in mice

The retention of 241Am in mice 48 h after administration by gavage is reported here. The 241Am was given to mice in the form of either 241Am nitrate or 241Am citrate. The 241Am was also injected into rats in the same form. The homogenized livers of those rats were subsequently administered by gavage to another group of mice. The retention of 241Am citrate was 1.5 X 10(-2)% of the original dose and was the highest among the compounds examined. The retention of biologically incorporated 241Am into the liver as 241Am nitrate and as 241Am citrate was 2.4 X 10(-3) and 2.6 X 10(-3)%, respectively, and was similar to the retention of 241Am nitrate, which was 2.8 X 10(-3)%. The ratio of the retention in the carcass to that in the liver for the 241Am citrate was lower than that of the 241Am nitrate and the biologically incorporated 241Am. This difference indicates that the distribution of 241Am in the animal body depends on the chemical form administered. The retention of liver-incorporated 241Am as citrate after autolysis of the liver is similar to that of fresh liver-incorporated 241Am citrate.     

妊娠兔胎盘细胞凋亡及凋亡相关基因Bcl-2和Bax表达的动态变化

以新西兰雌兔为动物模型,研究妊娠期间胎盘细胞凋亡及其凋亡调控蛋白Bcl-2和Bax表达的动态变化.基因组DNA凝胶电泳实验检测到妊娠中期和晚期胎盘基因组DNA中出现典型的凋亡特征——DNA梯带,而且DNA断裂值在妊娠早、中、晚期分别为：0.14、0.49和1.43,与妊娠早期相比,妊娠中、晚期胎盘基因组DNA断裂值有显著性增加.TUNEL实验和活化caspase-3的免疫定位实验表明,在妊娠早期胎盘中存在细胞凋亡,而且在各妊娠期中细胞凋亡主要发生于合体滋养层.免疫印迹法分析表明,Bcl-2和Bax随妊娠的进行其表达量明显增加,Bax∶Bcl-2比值在妊娠早、中、晚期分别为：0.89,0.91和1.25,呈增加趋势.实验结果说明,在兔正常妊娠中,胎盘合体滋养层细胞发生凋亡,且随妊娠的进行,凋亡细胞数量增多,胎盘细胞凋亡主要与细胞中Bax∶Bcl-2的比例相关.     

妊娠兔胎盘细胞凋亡及凋亡相关基因Bcl-2和Bax表达的动态变化

以新西兰雌兔为动物模型。研究妊娠期间胎盘细胞凋亡及其凋亡调控蛋白Bcl-2和Bax表达的动态变化,基因组DNA凝胶电泳实验检测到妊娠中期和晚期胎盘基因组DNA中出现典型的凋亡特征-DNA梯带,而且DNA断裂值在妊娠早、中、晚期分别为：0.14,0.49和1.43,与妊娠早期相比,妊娠中,晚期胎盘基因组DNA断裂值有显著性增加,TUNEL实验和活化caspase-3的免疫定位实验表明,在妊娠早期胎盘中存在细胞凋亡,而且在各妊娠期中细胞凋亡主要发生于合体滋养层,免疫印迹法分析表明,Bcl-2和Bax随妊娠的进行其表达量明显增加,Bax:Bcl-2比值在妊娠早、中、晚期分别为：0.89,0.91和1.25,呈增加趋势,实验结果说明,在兔正常妊娠中,胎盘合体滋养层细胞发生凋亡,且随妊娠的进行,凋亡细胞数量增多,胎盘细胞凋亡主要与细胞中Bax:Bcl-2的比例相关。     

Prevention of implantation by antiprogesterone

If progesterone (P) is indispensable in the protection of normal pregnancy during the pre-implantation period, then treatment with antiP (AP), should prevent implantation. The validity of this premise has been examined in the rat model, using the synthetic steroid: Isoxazol. This AP inhibits the conversion of pregnenolone to P, by inhibiting the enzyme 3β-HSDH. In an earlier study, a single oral dose of 2.5 mg Isoxazol invariably interrupted pregnancy shortly after implantation and 20 mg predictably provoked parturition preterm. In the present study, conducted between days 0 and 4 of the pre-implantation period, a single oral dose of 20 to 100 mg Isoxazol has been administered to spermpositive rats. The controls were treated with vehicle only. At day 4, when the blastocysts are already loosely attached to the endometrium, 40 mg Isoxazol compromised normal implantation, as a rule, and the conceptuses became resorbed. At day 3, when the morulas enter the uterus, this dose had a moderate effect only while 60 mg increased efficacy and 100 mg prevented the implantation of most blastocysts. As in the previous studies a single dose of AP provoked a drastic P withdrawal (Pw). The premise that it was Pw and not some side effect of Isoxazol which intercepted normal implantation was verified by the demonstration that the prevention of the AP-induced Pw, by P treatment, prevented the antifertility action of Isoxazol.