体外受精胚移植後のプロジェステロン投与が偽妊娠18日目マウスの生存着床胎仔数、胎仔重量、胎盤重量および胎盤組織構造に及ぼす影響

The prenatal toxic effects of contaminated vacuum pump oil (Sample A) and solid waste products (Samples B and C) originating from aluminum plasma etching processes in semiconductor manufacturing were investigated. Three strains of pregnant mice with different degrees of sensitivity during organogenesis (days 6-15 of gestation) were treated daily with 1000 mglkg b.w. (Sample A), 500 or 750 mg/kg b.w. (Sample B), and 250, 500, or 750 mg/kg b.w. (Sample C). On day 18 of pregnancy, the animals were killed and examined for gross changes, number and weight of live fetuses, as well as the number of postimplantation losses and malformations. Analytical data showed that the investigated wastes contained various halogenated hydrocarbons and inorganic compounds. Sample A revealed no signs of prenatal toxic action. In contrast, administration of Samples B and C caused strong prenatal toxic effects. The number of live fetuses declined in a dose--related manner, and evidence of intrauterine growth retardation was noted in fetuses that survived to day 18. The number of fetuses with malformations (only cleft palates) rose significantly in accordance with the doses and sensitivity of the strains (> 95 % of the fetuses of the most sensitive strain after 750 mg/kg; 85% after 500 mg/kg).

Little is known about the impact of high-normal range of 25-hydroxyvitamin D [25(OH)D] on reproductive function. The aim of this study was to investigate the effect of different dose vitamin D supplementation in female mice on the pregnancy outcomes. Three groups of female mice were fed with fodder containing different dose of vitamin D at both pre-gestational and gestational stages. Serum 25(OH)D and calcium concentrations were monitored. The expression levels of vitamin D receptor (VDR) mRNA and protein in placenta were determined by real-time RT-PCR and western blot. Pregnancy outcomes were evaluated and compared among the three groups. Compared with the medium and low dose groups, serum 25(OH)D concentration was significantly increased and approximated to high-normal range in the high dose group (pre-gestational: 81.3±5.75 vs 52.8±6.24 and 25.0±3.99 ng/mL; gestational: 86.8±5.99 vs 52.6±9.29 and 27.9±4.96 ng/mL, respectively; all p<0.001). Interestingly, the average number of live fetuses per litter was much larger in the high dose group than in other two groups (19.8±5.31 vs 13.8±1.30 and 12.8±3.55 respectively, both p<0.05). However, no significant differences of the expression levels of VDR mRNA and protein in placenta were identified among the three groups. Supplementation of high dose vitamin D can enhance the female mice reproductive function. Further study is warranted to explore the mechanism by which high level of 25(OH)D in female mice increases the number of fetuses.

Five groups of pregnant Wistar rats were injected intraperitoneally with a single dose of semicarbazide (SC) on day 5, 7, 10, 13, or 15 of gestation. The lots in each group received either 50, 75, 100 or 150 mg/kg SC. A sixth group received 17 mg/kg of the drug during the entire course of pregnancy. SC produced a significantly smaller number of live fetuses with respect to controls. This toxic effect after injection at days 7 and 10 of gestation was highest for all single doses. The mean of fetal weight decreased with respect to controls with almost all of the SC treatment studied. The number of implantations and live fetuses was significantly decreased in the rats receiving the continuous treatment. Most abnormalities in the 21-day-old fetuses were found in the brain, kidney, intestines and liver; skeletal anomalies were seen in the skull, sternum and ribs. SC also produced high postnatal mortality rates during the first month of life with the single doses as well as with the continuous treatment. Thus, SC produced signs of toxicity and/or teratogenic effects in rats with all doses administered.

Comparison of fetal toxicity of various multi-wall carbon nanotubes in mice

The developmental toxicity of uranium in mice

Exposure of pregnant outbred CD-1 mice to methanol during the period of gastrulation results in exencephaly, cleft palate, and cervical vertebra malformations [Rogers and Mole, Teratology 55: 364, 1997], while inbred C57BL/6J mice are sensitive to the teratogenicity of ethanol. C57BL/6J fetuses exhibit the holoprosencephaly spectrum of malformations after maternal exposure to ethanol during gastrulation, but the sensitivity of C57BL/6J mice to methanol-induced teratogenesis has not been previously described. Pregnant C57BL/6J mice were administered two i.p. injections totaling 3.4 or 4.9 g/kg methanol or distilled water four hrs apart on gestation day 'GD' 7. On GD 17, litters were examined for numbers of live, dead and resorbed conceptuses, fetuses were weighed as a litter and examined externally, and all fetuses were double stained for skeletal analysis. No maternal intoxication was apparent, but the high dosage level caused a transient deficit in maternal weight gain. The number of live fetuses per litter was reduced at both dosages of methanol, and fetal weight was lower in the high dosage group. Craniofacial defects were observed in 55.8% of fetuses in the low dosage group and 91.0% of fetuses in the high dosage group, including micro/anophthalmia, holoprosencephaly, facial clefts and gross facial angenesis. Skeletal malformations, particularly of the cervical vertebrae, were observed at both dosages of methanol, and were similar to those previously reported in the CD-1 mouse following methanol exposure. The types of craniofacial malformations induced in the C57BL/6J mouse by methanol indicate that methanol and ethanol have common targets and may have common modes of action.

Morinda citrifolia (noni) fruit juice use has increased greatly within the past decade, with more than 80,000,000 liters being consumed world wide. With increasing widespread use and the potential use among pregnant women, a prenatal developmental toxicity test was conducted to further evaluate the safety of noni juice. Freeze-dried noni fruit puree from French Polynesia was administered daily by gastric intubation to separate dose groups (n = 12) of pregnant Sprague Dawley rats at 1.72, 3.43, and 6.86 g/kg body weight, with a control group receiving water in place of noni. The dose schedule was followed from the first day of gestation until one day prior to expected delivery, 21 days. There were no symptoms of toxicity in the pregnant dams. There was no difference between the control and any noni group in the number of live fetuses, resorptions, fetal weight and length, or skeletal abnormalities. No dead fetuses, gross external malformations, or internal organ defects were observed in any group. These findings do not indicate that toxicity from noni juice to developing embryos and fetuses is expected.

Zona-free embryos at the 4-cell stage were classified into four types according to the total points of contact between the 4 blastomeres. Types A, B, C, and D had 3, 4, 5, and 6 points of contact, respectively. Embryos of these types were cultured individually in 20 microliters of Whitten's medium. Blastocysts derived from types A and D embryos at the 4-cell stage were transferred and observed on Day 17 of gestation. The number of live fetuses was significantly lower for type A than for type D embryos (p < 0.05). In spite of the removal of the zone pellucida, both types A and D blastocysts had cell numbers similar to those in zona-intact control embryos at 96 h after insemination. However, type A embryos had fewer (p < 0.05) inner cell mass (ICM) cells than did either the zona-intact control or type D embryos. Type D embryos did not have significantly fewer ICM than did the zona-intact control. Our data show that the cell association of zona-free embryos at the 4-cell stage influences differentiation of cells within the ICM and thus affects subsequent embryonic development. We suggest that one role of the zona pellucida after fertilization, in addition to protecting the preimplantation embryo, is to maintain the cell arrangement of 4-cell stage embryos to ensure subsequent successful cell lineage.

Characterization of pregnancy outcome following thiram-induced ovulatory delay in the female rat

Integrins regulate adhesion at the foeto-maternal interface by interacting with secreted phosphoprotein 1 (SPP1) and fibronectin (FN). It is hypothesised that impaired foetal growth of ‘runt’ piglets is linked to altered integrin signalling at the foeto-maternal interface. Placental and endometrial samples associated with the lightest and closest to mean litter weight (CTMLW) (gestational day (GD18, 30, 45, 60 and 90), of both sex (GD30, 45, 60 and 90) (n = 5–8 litters/GD), Large White × Landrace conceptuses or foetuses were obtained. The mRNA expression of the integrin subunits (ITG) ITGA2, ITGAV, ITGB1, ITGB3, ITGB5, ITGB6, ITGB8, SPP1 and FN was quantified by qPCR. Temporal changes in mRNA expression were observed, with different profiles in the two tissues. Endometrial ITGB1 (P ≤ 0.05, GD45) and SPP1 (P ≤ 0.05, all GD combined and GD60) expression was decreased in samples supplying the lightest compared to the CTMLW foetuses. Placentas supplying female foetuses had decreased expression of ITGB6 (GD45, P ≤ 0.05) and FN (GD90, P ≤ 0.05) compared to those supplying male foetuses. Endometrial samples supplying females had increased ITGB3 (P ≤ 0.05, GD60) and FN (P ≤ 0.05, GD30) expression and decreased SPP1 (P ≤ 0.05, GD60) expression compared to male foetuses. Correlations between mean within-gilt mRNA expression and percentage prenatal survival, number of live foetuses or conceptuses and percentage male foetuses were observed. This study has highlighted novel and dynamic associations between foetal size, sex and integrin subunit mRNA expression at the porcine foeto-maternal interface. Further studies should be performed to improve the understanding of the mechanisms behind these novel findings.

High Dietary Folate Supplementation Affects Gestational Development and Dietary Protein Utilization in Rats

&lt;p&gt;Pregnancy is associated with increased nutritional needs due to the physiologic changes of the female and the metabolic demands of the embryo/fetus. The use of chelating compounds with high biological activity increased the fertility of female rats by stimulation metabolism and functional activity of the reproductive system. Manganese is an essential element utilized by antioxidants, including superoxide dismutase (MnSOD), and others metalloenzymes that take part in reduction reactions, in multiple physiological processes including reproductive system. The aim of the research was to determine the effect of subcutaneous injections of Mn glutamate in liposomal forms on the reproductive system and the process of embryogenesis of experimental female rat.&lt;/p&gt; &lt;p&gt;The study was conducted on female rats aged 2.5-3 months with body weight of 180-200 g. Rats with dated gestation were divided into three groups: two experimental and control. Female rabbits of the 1&lt;sup&gt;th&lt;/sup&gt; experimental group were subcutaneous injected of 2 mg/ml for Mn glutamate in liposomal form one week before fertilization and the animals of the 2&lt;sup&gt;th&lt;/sup&gt; group were obtained the same preparation during fertilization. Rats were euthanized on the twentieth day, ovariens were singled out of fiber, visual inspection and counting the number of yellow bodies were performed, absolute and relative mass indexes were determined, Mn glutamate influence index was calculated.&lt;/p&gt; &lt;p&gt;Experimental results showed that the administration of Mn glutamate 7 days before fertilization and during fertilization significant increased the number of corpora lutea of pregnancy (p&amp;lt;0,001), number of live fetuses (p&amp;lt;0,001) due to the decrease in general and pre-implantation embryonic mortality compared with the control group. The experimental results showed improvement in key indicators of embryonic development. We observed significant increase in the number of implanted embryos on 1 female at 10,7±0,26 and 11,3±0,21 (p&amp;lt;0,001) (9,4±0,16 vs. control group) and decrease of the number of resorption in the female rats treated with Mn glutamate as compared with the control group. The results suggest a beneficial effect on the course of Mn glutamate embryogenesis of experimental animals.&lt;/p&gt; &lt;p&gt;&lt;em&gt;Key words: glutamate manganese, pregnancy, embryogenesis, liposomal preparation&lt;/em&gt;&lt;/p&gt;

During the past 9 years of reproductive and developmental toxicity studies in Sprague-Dawley rat, we noticed that the average fetal body weight on day 20 of gestation in 81 control groups fluctuated significantly from study to study. The other parameters such as number of implants, resorption rats and number of live fetuses were relatively stable. With information cooperatively given by the animal supplier, we could pin down the possibility of the fluctuation. The animal supplier introduced Sprague-Dawley rats into Japan from the U. S. twice in the past. The documents we analyzed indicated that the fluctuation in fetal body weight was caused by different two colonies which were introduced into Japan at the different times.

The exposure to nickel chloride (NiCl₂) can cause hematotoxicity and hepatotoxicity and canaffect development. The present study pertains to the protective effect of selenium (Se) against NiCl₂-induced toxicity in preimplanted Wistar albino rats. The subcutaneous (s.c.) administration of 25 or 50 mg/kg of NiCl₂ to Wistar albino rats on day 3 of gestation induced an immediate and significant decrease in maternal body weight and anemia 2 days after treatment. In addition, an increase in plasma aspartate aminotransferase (AST) was observed. These effects were maintained on day 20 of gestation. Moreover, a significant increase in plasma alanine aminotransferase (ALT) levels was observed with the administration of 25 mg/kg of NiCl₂. Conversely, administration of 50 mg/kg of NiCl₂ by s.c. injection increased erythropoiesis at day 20 of gestation and decreased platelets counts. In addition, administration of 100 mg/kg of NiCl₂ markedly reduced the maternal body weight and number of live fetuses and increased fetal loss, predominantly at the end of the experimental period. All dose levels of NiCl₂ caused an alteration in the hepatic histoarchitecture. When 0.3-mg/kg Se was injected s.c. with 100-mg/kg NiCl₂, the levels of plasma AST and ALT and the structure of the liver were restored. Administration of 20 mg/L/day of NiCl₂ in the drinking water significantly reduced the maternal body weight at day five of gestation as well as erythropoiesis during the exposure period. The present study suggests that Se can counteract the nocuous effect of nickel on the liver; however this antioxidant did not prevent alterations in development and erythropoiesis.

Secretion of proteins by the endometrium of pigs during pregnancy is reported to be influenced by progesterone and estrogen. The effect of estrone treatment from d 30 to 45 of pregnancy on endometrial protein secretion and uterine capacity was tested in unilaterally hysterectomized-ovariectomized (UHO) gilts. Ten intact and 16 UHO crossbred gilts were mated and assigned to the following treatments: 1) intact controls, n = 10; 2) UHO, n = 8; and 3) UHO + estrone (E; two 150-mg implants, 60-d release, implanted on d 30 of gestation), n = 8. Gilts were killed on d 45 of pregnancy. A sample of allantoic fluid was collected from each conceptus. Blood and endometrial tissue samples were collected to evaluate estrone concentrations, and placental and endometrial tissues were incubated to evaluate protein secretion. Estrone treatment increased (P < .01) plasma and endometrial tissue estrone concentrations. Unilateral hysterectomy-ovariectomy decreased (P < .01) fetal survival. No effect of estrone was detected on the number of live fetuses, protein secretion by endometrial tissue in culture, or allantoic fluid protein, acid phosphatase, retinol binding protein, or retinol. Estrone treatment decreased uterine weight (P = .05) and allantoic fluid fructose concentrations (P < .05). After correction for allantoic fluid volume, allantoic fluid protein, retinol, and acid phosphatase activity were decreased (P < .05) in UHO-treated pigs. The UHO treatment did not affect allantoic fluid fructose concentrations. These results indicate that 1) estrone treatment from d 30 to 45 of pregnancy and at the dosage used did not alter endometrial protein secretion or fetal survival, and 2) UHO decreased the amount of endometrial proteins available to conceptuses.