The Influence of Polyploidy and Genome Composition on Genomic Imprinting in Mice

Genomic imprinting is an epigenetic mechanism that switches the expression of imprinted genes involved in normal embryonic growth and development in a parent-of-origin-specific manner. Changes inDNAmethylation statuses from polyploidization are a well characterized epigenetic modification in plants. However, how changes in ploidy affect both imprinted gene expression and methylation status in mammals remains unclear. To address this, we used quantitative real time PCR to analyze expression levels of imprinted genes in mouse tetraploid fetuses. We used bisulfite sequencing to assess the methylation statuses of differentially methylated regions (DMRs) that regulate imprinted gene expression in triploid and tetraploid fetuses. The nine imprinted genes H19, Gtl2, Dlk1, Igf2r, Grb10, Zim1, Peg3, Ndn, and Ipw were all unregulated; in particular, the expression of Zim1 was more than 10-fold higher, and the expression of Ipw was repressed in tetraploid fetuses. The methylation statuses of four DMRs H19, intergenic (IG), Igf2r, and Snrpn in tetraploid and triploid fetuses were similar to those in diploid fetuses. We also performed allele-specific RT-PCR sequencing to determine the alleles expressing the three imprinted genes Igf2, Gtl2, and Dlk1 in tetraploid fetuses. These three imprinted genes showed monoallelic expression in a parent-of-origin-specific manner. Expression of non-imprinted genes regulating neural cell development significantly decreased in tetraploid fetuses, which might have been associated with unregulated imprinted gene expression. This study provides the first detailed analysis of genomic imprinting in tetraploid fetuses, suggesting that imprinted gene expression is disrupted, but DNA methylation statuses of DMRs are stable following changes in ploidy in mammals

Study of embryotoxicity of mentha piperita l. during organogenesis in balb/c mice

Mentha piperita (Labiatae), commonly known as peppermint is a native Iranian herb which is used in folk medicine for various purposes. This study was carried out to reveal the teratogenic effect of Mentha piperita on mice fetuses. In this experimental study, pregnant Balb/c mice divided to four groups. Case group received 600 (treatment I) and 1200 (treatment II) mg/kg/day the hydroalcoholic extract of Mentha piperita during 6-15 of gestational days and one control group received normal saline during GD6-GD15 by gavages and other control group did not receive any matter during 6-15 of gestational days. Mice sacrificed at GD18 and embryos were collected. Macroscopic observation was done by stereomicroscope. 20 fetuses of each group were stained by Alizarin red-S and Alcian blue staining method. The Mean weight of fetuses decreased in treatment groups rather than control (P<0.05) but CRL there was no significant difference between treatments and controls groups. In the treatment I (600 mg/kg/day) and treatment II (1200 mg/kg/day), normal saline and control group, no gross congenital malformations were observed in fetuses. Treated fetuses also had no delayed bone ossification as determined by Alizarin red-S and Alcian blue staining method. This study showed that the hydroalcoholic extract of Mentha piperita (600 and 1200 mg/ kg/day) has no teratogenic effect in mice fetuses if used continuously during embryonic period

Three-dimensional cephalometric evaluation of maxillary growth following in utero repair of cleft lip and alveolar-like defects in the mid-gestational sheep model

Objective: To evaluate maxillary growth following in utero repair of surgically created cleft lip and alveolar (CLA)-like defects by means of three-dimensional (3D) computer tomographic (CT) cephalometric analysis in the mid-gestational sheep model. Methods: In 12 sheep fetuses a unilateral CLA-like defect was created in utero (untreated control group: 4 fetuses). Four different bone grafts were used for the alveolar defect closure. After euthanasia, CT scans of the skulls of the fetuses, 3D re-constructions, and a 3D-CT cephalometric analysis were performed. Results: The comparisons between the operated and nonoperated skull sides as well as of the maxillary asymmetry among the experimental groups revealed no statistically significant differences of the 12 variables used. Conclusions: None of the surgical approaches used for the in utero correction of CLA-like defects seem to affect significantly postsurgical maxillary growth; however, when bone graft healing takes place, a tendency for almost normal maxillary growth can be observed. Copyright (c) 2006 S. Karger AG, Basel

Early and Later Abortions: Ethics and Law

Most abortions occur early in pregnancy. I argue that these abortions, and so most abortions, are not morally wrong and that the best arguments given to think that these abortions are wrong are weak. I also argue that these abortions, and probably all abortions, should be legal. I begin by observing that people sometimes respond to the issue by describing the circumstances of abortion, not offering reasons for their views about those circumstances; I then dismiss “question-begging” arguments about abortion that merely assume the conclusions they are given to support; most importantly, I evaluate many arguments: both common, often-heard arguments and arguments developed by philosophers. My defense of abortion is based on facts about early fetuses’ not yet possessing consciousness or any mental life, awareness or feeling, as well as concerns about rights to one’s own body

Teratogenic effects of gabapentin on the skeletal system of Balb/C mice fetuses

Objectives: To evaluate the effects of gabapentin )GBP( administration on mice fetuses. Methods: This study was carried out in Birjand University of Medical Sciences during 2008. Thirty Balb/c pregnant mice were divided randomly into 3 groups: 2 experimental groups that received 25 mg/kg )I( and 50 mg/kg )II( of GBP intraperitoneally for the first 15 days of pregnancy, and a control group that received normal saline. External observations of day 18 fetuses and skeleton double staining were performed. Results: Both experimental groups showed similar disorders that can be categorized as the following: 1( decrease of fetal body weight and increase of fetal resorption, 2( macroscopic malformations, and 3( skeletal malformations. Fetal body weights were significantly lower, and fetus resorptions were significantly higher in both treated groups compared to the control group. Macroscopic malformations included exencephaly, limbs defects, brachygnathia, vertebral column deformity, and fetuses with severe retarded growth. Skeletal malformations included delayed ossification, scoliosis, calvaria deformity, and mandibular hypoplasia. Conclusion: This study revealed that GBP can induce previously unreported severe malformations if it is used continuously during the implantation, neurulation, and organogenesis stages of pregnancy. Therefore, it is suggested that great caution should be exercised in using GBP during the early stages of pregnancy until further studies are performed to better understand these effects

Defending the Distinction Between Pregnancy and Parenthood

In this paper, I respond to criticisms toward my account of the difference in moral status between fetuses and newborns. I show my critics have not adequately argued for their view that pregnant women participate in a parent-child relationship. While an important counterexample is raised against my account, this counterexample had already been dealt with in my original paper. Because the criticisms against my account lack argumentative support, they do not pose a problem for my account. I conclude the raised criticisms do not amount to a strong philosophical case against my account

Developmental toxic effects of ethylbenzene or toluene alone and in combination with butyl acetate in rats after inhalation exposure

First, the developmental toxic potential of n-butyl acetate (BA) was examined in Sprague-Dawley rats following whole body inhalation exposure, 6 h day-1, from day 6 to 20 of gestation, at concentrations of 0, 500, 1000, 2000 and 3000 ppm. Maternal toxicity was evidenced by significant decreases in body weight gain at 2000 and 3000 ppm, and by reduced food consumption at 1000 ppm and higher concentrations. The effects on prenatal development were limited to a significant decrease in fetal weight at 3000 ppm. Thus, inhaled BA was not a selective developmental toxicant. In the second part of this study, the developmental toxic effects of simultaneous exposures to ethylbenzene (EB) and BA, or to toluene (TOL) and BA were evaluated. Pregnant rats were administered EB (0, 250 or 1000 ppm) and BA (0, 500 or 1500 ppm), or TOL (0, 500 or 1500 ppm) and BA (0, 500, 1500 ppm), separately and in combinations, using a 2 × 2 factorial design. The maternal weight gain was reduced after exposure to 1000 ppm EB, to 1500 ppm BA, or to 1500 ppm TOL, either alone or in binary combinations. A significant reduction of fetal weight was associated with exposure to 1000 ppm EB alone, to either mixtures of EB with BA, or to 1500 ppm TOL alone or combined with BA at either concentration. No embryolethal or teratogenic effects were observed whatever the exposure. There was no evidence of interaction between EB and BA or between TOL and BA in causing maternal or developmental effects. Copyright © 2006 John Wiley & Sons, Ltd

Teratogenic effects of gabapentin on neural tube and limb development in mice

[No abstract available

An Ethical Evaluation of Federal Norms for Fetal Experimentation

Father O\u27Rourke is Director of the Medical-Moral Department of the Catholic Hospital Association in St. Louis. In this article, he raises some questions regarding the work which was done by the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research