Search our Database of Scientific Publications and Authors

I’m looking for a

    548 results match your criteria Birth Defects Research Part B: Developmental and Reproductive Toxicology [Journal]

    1 OF 11

    Developmental toxicity studies of lumefantrine and artemether in rats and rabbits.
    Birth Defects Res B Dev Reprod Toxicol 2016 Dec;107(6):243-257
    Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA.
    The combination of artemether plus lumefantrine is a type of artemisinin-based combination therapy (ACT) recommended by the World Health Organization for uncomplicated falciparum malaria except in the first trimester of pregnancy. The first trimester restriction was based on the marked embryotoxicity in animals (including embryo death and cardiac and skeletal malformations) of artemisinins such as artesunate, dihydroartemisinin, and artemether. Before recommending ACTs for use in the first trimester, the World Health Organization has requested that all information relevant to the assessment of risk of ACTs to the embryo be made available to the public. Read More

    Lost in translation: The search for an in vitro screen for spermatogenic toxicity.
    Birth Defects Res B Dev Reprod Toxicol 2016 Dec 26;107(6):225-242. Epub 2016 Dec 26.
    Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden.
    The last two decades have seen an increasing search for in vitro models that can replace the use of animals for safety testing. We adapted the methods from a recent nonquantitative report of spermatogenesis occurring in ex vivo mouse testis explants and tried to develop them into a screening assay. The model consisted of small pieces of neonatal mouse testis (testis "chunks"), explanted and placed on pillars of agarose or chamber inserts, and cultured at the air-liquid interface. Read More

    Exposure to high-concentration oxygen in the neonatal period induces abnormal retinal vascular patterning in mice.
    Birth Defects Res B Dev Reprod Toxicol 2016 Dec 28;107(6):216-224. Epub 2016 Oct 28.
    Department of Molecular Pharmacology, Kitasato University School of Pharmaceutical Sciences, Minato-ku, Tokyo, Japan.
    The interruption of vascular development could cause structural and functional abnormalities in tissues. We have previously reported that short-term treatment of newborn mice with vascular endothelial growth factor (VEGF) receptor tyrosine kinase inhibitors induces abnormal retinal vascular growth and patterns. An exposure of neonatal mice to high-concentration oxygen disturbs normal retinal vascular development. Read More

    Effect of fructose on the phosphorylation of AMP-activated protein kinase and acetyl-CoA carboxylase in HepG2 cells stimulated with placental lactogen.
    Birth Defects Res B Dev Reprod Toxicol 2016 Aug 26;107(4-5):206-210. Epub 2016 Sep 26.
    Department of Nutrition, Aomori University of Health and Welfare, Aomori, Japan.
    Background: High fructose intake induces disruption of lipid metabolism via AMP-activated protein kinase (AMPK) signaling in the liver and peripheral tissues. Maternal lipid metabolism is physiologically altered by the activity of pregnancy hormones such as human placental lactogen (PL). To elucidate the influence of high fructose intake on hepatic lipid metabolism during pregnancy, we examined the effects of fructose on lipid metabolism via the AMPK pathway in hepatocytes stimulated with PL. Read More

    Reproductive and neurobehavioral effects of maternal exposure to piperonyl butoxide (PBO) in F -generation mice.
    Birth Defects Res B Dev Reprod Toxicol 2016 Aug 19;107(4-5):195-205. Epub 2016 Sep 19.
    Division of Toxicology, Department of Pharmaceutical and Environmental Sciences, Tokyo Metropolitan Institute of Public Health, Tokyo, Japan.
    Female mice were exposed maternally to piperonyl butoxide (PBO) through diet to provide levels of 0 (control), 0.015, 0.03, and 0. Read More

    Goldilocks' Determination of What New In Vivo Data are "Just Right" for Different Common Drug Development Scenarios, Part 1.
    Birth Defects Res B Dev Reprod Toxicol 2016 Aug 6;107(4-5):185-194. Epub 2016 Sep 6.
    Developmental and Reproductive Toxicology CoE, Pfizer, Inc, Groton, CT, USA.
    As alternative models and scientific advancements improve the ability to predict developmental toxicity, the challenge is how to best use this information to support safe use of pharmaceuticals in humans. While in vivo experimental data are often expected, there are other important considerations that drive the impact of developmental toxicity data to human risk assessment and product labeling. These considerations include three key elements: (1) the drug's likelihood of producing off-target toxicities, (2) risk tolerance of adverse effects based on indication and patient population, and (3) how much is known about the effects of modulating the target in pregnancy and developmental biology. Read More

    TGF-β1 monoclonal antibody: Assessment of embryo-fetal toxicity in rats and rabbits.
    Birth Defects Res B Dev Reprod Toxicol 2016 Aug 12;107(4-5):174-184. Epub 2016 Aug 12.
    Lilly Research Laboratories, Corporate Center, Indianapolis, IN, USA.
    A humanized monoclonal antibody targeting transforming growth factor β1 (TGF-β1 mab) has been used in development for the treatment of chronic kidney disease. Embryo-fetal development studies were conducted in rats and rabbits using 30 and 25 animals per group, respectively. The TGF-β1 mab was administered subcutaneously to rats at 0, 2, or 50 mg/kg/dose on gestation days (GDs) 6, 10, and 14 and intravenously to rabbits at 0 or 3 mg/kg/dose on GDs 7, 12 to 19, and at 30 mg/kg/dose on GDs 7, 12, 14, 16, and 18. Read More

    Ovarian Stimulators, Intrauterine Insemination, and Assisted Reproductive Technologies Use and the Risk of Major Congenital Malformations-The AtRISK Study.
    Birth Defects Res B Dev Reprod Toxicol 2016 Jun 13;107(3):136-47. Epub 2016 Jun 13.
    Research Center, CHU Ste-Justine, Montreal, Quebec, Canada.
    Objective: To quantify the risk of major congenital malformations (MCMs) associated with the use of ovarian stimulators alone, intrauterine insemination (IUI), and assisted reproductive technologies (ARTs).

    Methods: We conducted a case-control analysis using a birth cohort, built with the linkage of data obtained by a self-administered questionnaire, medical, pharmaceutic, and birth databases. Cases were pregnancies with at least one live birth with an MCM. Read More

    Gestational and Early Postnatal Exposure to an Environmentally Relevant Mixture of Brominated Flame Retardants: General Toxicity and Skeletal Variations.
    Birth Defects Res B Dev Reprod Toxicol 2016 Jun 10;107(3):157-68. Epub 2016 Jun 10.
    Environmental Health Science & Research Bureau, Health Canada, Ottawa, Ontario, Canada.
    Brominated flame retardants (BFRs) are stable environmental contaminants known to exert endocrine-disrupting effects. Developmental exposure to polybrominated diphenyl ethers (PBDEs) is correlated with impaired thyroid hormone signaling, as well as estrogenic and anti-androgenic effects. As previous studies have focused on a single congener or technical mixture, the purpose of the current study was to examine the effects of gestational and early postnatal exposure to an environmentally relevant mixture of BFRs designed to reflect house dust levels of PBDEs and hexabromocyclododecane on postnatal developmental outcomes. Read More

    Preclinical Reproductive and Developmental Toxicity Profile of a Glycine Transporter Type 1 (Glyt1) Inhibitor.
    Birth Defects Res B Dev Reprod Toxicol 2016 Jun 24;107(3):148-56. Epub 2016 May 24.
    Roche Pharmaceutical Research and Early Development, F. Hoffmann-La-Roche, Basel, Switzerland.
    Bitopertin is a glycine type 1 (GlyT1) inhibitor intended for the treatment of psychiatric disorders. The principle adverse effect in the regulatory reproductive toxicity studies was peri-natal pup death when rat dams were treated during parturition at a dose resulting in five-times the human therapeutic exposure (AUC). Cessation of dosing two days before parturition prevented the pup deaths. Read More

    Developmental Toxicity Studies with Pregabalin in Rats: Significance of Alterations in Skull Bone Morphology.
    Birth Defects Res B Dev Reprod Toxicol 2016 Apr 13;107(2):94-107. Epub 2016 Apr 13.
    Pfizer Worldwide Research and Development, Drug Safety Research and Development, Andover, Massachusetts.
    Pregabalin was administered to pregnant Wistar rats during organogenesis to evaluate potential developmental toxicity. In an embryo-fetal development study, compared with controls, fetuses from pregabalin-treated rats exhibited increased incidence of jugal fused to maxilla (pregabalin 1250 and 2500 mg/kg) and fusion of the nasal sutures (pregabalin 2500 mg/kg). The alterations in skull development occurred in the presence of maternal toxicity (reduced body weight gain) and developmental toxicity (reduced fetal body weight and increased skeletal variations), and were initially classified as malformations. Read More

    An Evaluation of the Impact of PD-1 Pathway Blockade on Reproductive Safety of Therapeutic PD-1 Inhibitors.
    Birth Defects Res B Dev Reprod Toxicol 2016 Apr 7;107(2):108-19. Epub 2016 Apr 7.
    Merck Research Laboratories, West Point, Pennsylvania.
    This report discusses the principles of reproductive toxicity risk assessment for biopharmaceuticals blocking the PD-1/programmed cell death ligand 1 (PD-L1) pathway, which have been developed for the treatment of patients with advanced malignancies. The PD-1/PD-L1 pathway is a T-cell co-inhibitory pathway that normally maintains immune tolerance to self. Its role in pregnancy is to maintain immune tolerance to the fetal allograft. Read More

    Embryo-Fetal Developmental Toxicity Studies with Pregabalin in Mice and Rabbits.
    Birth Defects Res B Dev Reprod Toxicol 2016 Apr 4;107(2):85-93. Epub 2016 Apr 4.
    Pfizer Worldwide Research and Development, Drug Safety Research and Development, Groton, Connecticut.
    Pregabalin was evaluated for potential developmental toxicity in mice and rabbits. Pregabalin was administered once daily by oral gavage to female albino mice (500, 1250, or 2500 mg/kg) and New Zealand White rabbits (250, 500, or 1250 mg/kg) during organogenesis (gestation day 6 through 15 [mice] or 6 through 20 [rabbits]). Fetuses were evaluated for viability, growth, and morphological development. Read More

    A Probability Analysis of Historical Pregnancy and Fetal Data from Dutch Belted and New Zealand White Rabbit Strains from Embryo-Fetal Development Studies.
    Birth Defects Res B Dev Reprod Toxicol 2016 Apr 31;107(2):76-84. Epub 2016 Mar 31.
    GlaxoSmithKline, King of Prussia, PA.
    Embryo-fetal development (EFD) studies, typically in pregnant rats and rabbits, are conducted prior to enrolling females of reproductive age in clinical trials. Common rabbit strains used are the New Zealand White (NZW) and Dutch Belted (DB). As fetal abnormalities can occur in all groups, including controls, Historical Control Data (HCD) is compiled using data from control groups of EFD studies, and is used along with each study's concurrent control group to help determine whether fetal abnormalities are caused by the test article or are part of background incidences. Read More

    Mechanism of Developmental Effects in Rats Caused by an N-Phenylimide Herbicide: Transient Fetal Anemia and Sequelae during Mid-to-Late Gestation.
    Birth Defects Res B Dev Reprod Toxicol 2016 Feb 10;107(1):45-59. Epub 2016 Feb 10.
    Department of Pediatrics, University of Washington, Seattle, Washington.
    Background: Rat developmental toxicity including embryolethality and teratogenicity (mainly ventricular septal defects [VSDs] and wavy ribs) was produced by an N-phenylimide herbicide that inhibits protoporphyrinogen oxidase (PPO) common to chlorophyll and heme biosynthesis. Major characteristics of the developmental toxicity included species difference between rats and rabbits, compound-specific difference among structurally similar herbicides, and sensitive period. Protoporphyrin accumulation in treated fetuses closely correlated with the major characteristics. Read More

    Investigation on Toxicity and Teratogenicity in Rats of a Retinoid-Polyamine Conjugate with Potent Anti-Inflammatory Properties.
    Birth Defects Res B Dev Reprod Toxicol 2016 Feb 13;107(1):32-44. Epub 2016 Jan 13.
    Department of Biochemistry, School of Medicine, University of Patras, Patras, Greece.
    Previous studies have shown that N(1),N(12)-bis(all-trans-retinoyl)spermine (RASP), a retinoid analog, inhibits RNase P activity and angiogenesis in the chicken embryo chorioallantoic membrane, demonstrates anti-tumor activity on prostate cancer cells, and acts as anti-inflammatory agent, being more effective and less toxic than all-trans retinoic acid. In an attempt to further characterize the biological profile of RASP, we tested its effects on organ toxicity and teratogenicity by daily oral gavage of RASP at a level of 50 mg/Kg of body weight in two generations of rats. We found that this compound does not induce changes to the body growth, the appearance of physical features, and the animal's reflexes. Read More

    Diabetes in the Cohen Rat Intensifies the Fetal Pancreatic Damage Induced by the Diabetogenic High Sucrose Low Copper Diet.
    Birth Defects Res B Dev Reprod Toxicol 2016 Feb 7;107(1):21-31. Epub 2016 Jan 7.
    Laboratory of Teratology, Department of Medical Neurobiology, Hadassah Medical School, Hebrew University of Jerusalem, Jerusalem, Israel.
    Intrauterine hyperglycemic environment could harm the fetus making it more susceptible to develop postnatal glucose intolerance. A possible mechanism is compromise of the fetal pancreatic development. We previously found that a high sucrose low copper diabetogenic diet induces type 2 diabetes in the Cohen diabetic sensitive rats, but not in the Sabra control rats. Read More

    A Developmental Toxicology Assay Platform for Screening Teratogenic Liability of Pharmaceutical Compounds.
    Birth Defects Res B Dev Reprod Toxicol 2016 Feb 5;107(1):4-20. Epub 2016 Jan 5.
    Discovery Toxicology Group, Bristol Myers-Squibb, Hopewell, New Jersey.
    Increasing need for proactive safety optimization of pharmaceutical compounds has led to generation and/or refinement of in vitro developmental toxicology assays. Our laboratory has developed three in vitro developmental toxicology assays to assess teratogenic liability of pharmaceutical compounds. These assays included a mouse molecular embryonic stem cell assay (MESCA), a dechorionated zebrafish embryo culture (ZEC) assay, and a streamlined rat whole embryo culture (rWEC) assay. Read More

    Advanced Paternal Age and Risk of Musculoskeletal Congenital Anomalies in Offspring.
    Birth Defects Res B Dev Reprod Toxicol 2015 Dec 10;104(6):273-80. Epub 2015 Dec 10.
    Section of Social Medicine, Department of Public Health, University of Copenhagen, Denmark.
    Objective: Previous research suggests that advanced paternal age increases the risk of musculoskeletal congenital anomalies (CAs) in offspring, but findings are inconsistent. This study aims to investigate the risk of musculoskeletal CAs according to paternal age at birth in an unselected population covering cohort of children.

    Study Design: A register-based prospective study of 1,605,885 children born in Denmark, 1978-2004, using information from record-linked health and administrative registers. Read More

    Visualizing Compound Distribution during Zebrafish Embryo Development: The Effects of Lipophilicity and DMSO.
    Birth Defects Res B Dev Reprod Toxicol 2015 Dec 11;104(6):253-72. Epub 2015 Dec 11.
    WIL Research Europe B.V, Hambakenwetering 7, 's-Hertogenbosch, The Netherlands.
    The predictability of the zebrafish embryo model is highly influenced by internal exposure of the embryo/larva. As compound uptake is likely to be influenced by factors such as lipophilicity, solvent use, and chorion presence, this article focuses on investigating their effects on compound distribution within the zebrafish embryo. To visualize compound uptake and distribution, zebrafish embryos were exposed for 96 hr, starting at 4 hr postfertilization, to water-soluble dyes: Schiff's reagent (logP -4. Read More

    Early Vaginal Opening in Juvenile Female Rats Given BRAF-Inhibitor Dabrafenib Is Not Associated with Early Physiologic Sexual Maturation.
    Birth Defects Res B Dev Reprod Toxicol 2015 Dec 1;104(6):244-52. Epub 2015 Dec 1.
    Safety Assessment, GlaxoSmithKline, King of Prussia, Pennsylvania.
    Dabrafenib (DAB), an inhibitor of BRAF kinase activity, is approved for metastatic melanoma with a BRAF V600E mutation. In support of pediatric cancer development, a nonclinical juvenile rat toxicity study was conducted in which females had early vaginal opening (VO). It was hypothesized that the early VO was not indicative of sexual maturation, but a result of a local effect on the vagina. Read More

    Exposure Duration-Dependent Ovarian Recovery in Methoxychlor-Treated Mice.
    Birth Defects Res B Dev Reprod Toxicol 2015 Dec 9;104(6):238-43. Epub 2015 Nov 9.
    Department of Comparative Biosciences, University of Illinois at Urbana-Champaign, Urbana, Illinois.
    The pesticide methoxychlor (MXC) is known to target ovarian antral follicles in the mouse. In previous in vivo studies, MXC administration for 20 days increased atresia, but did not affect female fertility immediately after dosing. Thus, we hypothesized that perhaps not enough time had elapsed between the onset of MXC-induced atresia and actual follicle loss to result in reduced fertility. Read More

    Effect of Age, Duration of Exposure, and Dose of Atrazine on Sexual Maturation and the Luteinizing Hormone Surge in the Female Sprague-Dawley Rat.
    Birth Defects Res B Dev Reprod Toxicol 2015 Oct 6;104(5):204-17. Epub 2015 Oct 6.
    Department of Basic Medical Sciences, University of Arizona College of Medicine, Phoenix, Arizona.
    Atrazine (ATZ) was administered daily by gavage to pregnant female Sprague Dawley rats at doses of 0, 6.25, 25 or 50 mg/kg/day, either during gestation, lactation and post-weaning (G/L/PW cohort) to F1 generation female offspring or only from postnatal day (PND 21) until five days after sexual maturation (vaginal opening) when the estrogen-primed, luteinizing hormone (LH) surge was evaluated (PW cohort). Additional subgroups of F1 females received the vehicle or ATZ from PND 21-133 or from PND 120-133. Read More

    Effects of Maternal Exposure to Piperonyl Butoxide (PBO) on Behavioral Development in F1-Generation Mice.
    Birth Defects Res B Dev Reprod Toxicol 2015 Dec 2;104(6):227-37. Epub 2015 Oct 2.
    Division of Toxicology, Tokyo Metropolitan Institute of Public Health, Shinjuku-ku, Tokyo, Japan.
    Female mice were exposed maternally to piperonyl butoxide (PBO) through diet to provide dietary levels of 0% (control), 0.01%, 0.03%, and 0. Read More

    The Effect of Dofetilide on the Heart Rate of GD11 and GD13 Rat Embryos, in vivo, Using Ultrasound.
    Birth Defects Res B Dev Reprod Toxicol 2015 Oct 24;104(5):196-203. Epub 2015 Sep 24.
    Department of Anatomy and Histology, The University of Sydney, New South Wales, Australia.
    Background: There are a wide range of drugs including antidepressants, anticonvulsants and antipsychotics that cause embryonic bradycardia in vitro but it is unknown if they have a similar effect in vivo. One way to verify whether these in vitro findings are replicated in vivo is by the use of ultrasound examination of dosed pregnant rats. We tested this by examining the effect of dofetilide on embryonic heart rate (HR) in vivo using ultrasound. Read More

    Impact of Early Postnatal NSAID Treatment on Nephrogenesis in Wistar Rats.
    Birth Defects Res B Dev Reprod Toxicol 2015 Oct 16;104(5):218-26. Epub 2015 Sep 16.
    Department of Pediatric Nephrology, Radboud University Medical Center, Nijmegen, the Netherlands.
    Background: Prematurely born children with patent ductus arteriosus are treated with ibuprofen or indomethacin, which may inhibit kidney development. We determined whether clinical doses affected kidney development and function, with or without extrauterine growth retardation.

    Methods: Wistar rats were cross-fostered in normal food (NF) or food restricted (FR) litters at postnatal day (PND) 2. Read More

    Effect of Himatanthus sucuuba in Maternal Reproductive Outcome and Fetal Anomaly Frequency in Rats.
    Birth Defects Res B Dev Reprod Toxicol 2015 Oct 4;104(5):190-5. Epub 2015 Sep 4.
    Laboratory of System Physiology and Reproductive Toxicology, Institute of Biological and Health Sciences, Federal University of Mato Grosso (UFMT), Barra do Garças, Mato Grosso State, Brazil.
    The aim of this study was to evaluate the effect of Himatanthus sucuuba on the maternal reproductive outcome and fetal anomaly incidence in rats. Pregnant rats were randomly divided into three experimental groups as follows: Control = treated with water (vehicle), treated 250 = treated with H. sucuuba at dose 250 mg/kg, and treated 500 = treated with H. Read More

    The Effect of Exposure to Atrazine on Dopaminergic Development in Pubertal Male SD Rats.
    Birth Defects Res B Dev Reprod Toxicol 2015 Oct 1;104(5):184-9. Epub 2015 Sep 1.
    Department of Toxicology, College of Public Health, Harbin Medical University, Harbin, Heilongjiang Province, PR China.
    Atrazine (ATR, 2-chloro-4-ethylamino-6-isopropylamino-s-triazine) is used worldwide as a herbicide, and its presence in the environment has resulted in documented human exposure. A lack of strong evidence for genetic heritability of idiopathic Parkinson's disease has focused attention on environmental toxicants in the disease etiology, particularly agrichemicals. Parkinson's disease is associated with advanced age and is characterized by the degeneration of dopaminergic neurons, but it is unclear whether specific neuronal damage could result from insults during development. Read More

    Valproic Acid Induces the Hyperacetylation of P53, Expression of P53 Target Genes, and Markers of the Intrinsic Apoptotic Pathway in Midorganogenesis Murine Limbs.
    Birth Defects Res B Dev Reprod Toxicol 2015 Oct 25;104(5):177-83. Epub 2015 Aug 25.
    Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada.
    In utero exposure to valproic acid (VPA), an anticonvulsant and histone deacetylase inhibitor (HDACi), increases the risk of congenital malformations. Although the mechanisms leading to the teratogenicity of VPA remain unsolved, several HDAC inhibitors increase cell death in cancer cell lines and embryonic tissues. Moreover, P53, the master regulator of apoptosis, is an established HDAC target. Read More

    Reproductive and Developmental Toxicity of Orally Administered Botanical Composition, UP446-Part I: Effects on Embryo-Fetal Development in New Zealand White Rabbits and Sprague Dawley Rats.
    Birth Defects Res B Dev Reprod Toxicol 2015 Aug 24;104(4):141-52. Epub 2015 Aug 24.
    Unigen Inc, Seattle, Washington.
    The pharmacotoxicology impacts of dietary supplements taken at the time of pregnancy have remained alarming since women are the frequent herbal medicine users in many countries as a complement to the conventional pregnancy management. The use of herbal medicines and diet supplements in expectant mothers linked closely to the health of the childbearing mothers and the fetuses where the lack of developmental safety data imposes a challenge to make the right choices. Here, we describe the potential adverse effects of UP446, a standardized bioflavonoid composition from the roots of Scutellaria baicalensis and the heartwoods of Acacia catechu, on embryo-fetal development following maternal exposure during the critical period of major organogenesis in rabbits and rats. Read More

    Developmental Toxicity and Fertility Assessment in Rabbits with Tabalumab: A Human IgG4 Monoclonal Antibody.
    Birth Defects Res B Dev Reprod Toxicol 2015 Jun 20;104(3):117-28. Epub 2015 Jul 20.
    WIL Research, Ashland, Ohio.
    Tabalumab is a human immunoglobulin G subclass 4 monoclonal antibody that has been under development for autoimmune disorders. Tabalumab has full neutralizing activity against both soluble and membrane B-cell activating factor, a B-cell survival factor. The objectives of these studies were to assess the effects of tabalumab on embryo-fetal development and on male (M) and female (F) fertility in rabbits, a pharmacologically relevant species. Read More

    An Enhanced Pre- and Postnatal Development Study in Cynomolgus Monkeys with Tabalumab: A Human IgG4 Monoclonal Antibody.
    Birth Defects Res B Dev Reprod Toxicol 2015 Jun 20;104(3):100-16. Epub 2015 Jul 20.
    Charles River Laboratories, Reno, Nevada.
    Tabalumab, a human IgG4 monoclonal antibody (mAb) with neutralizing activity against both soluble and membrane B-cell activating factor (BAFF), has been under development for the treatment of autoimmune diseases. The purpose of this study was to determine the potential adverse effects of maternal tabalumab exposure on pregnancy, parturition, and lactation of the mothers and on the growth, viability, and development of the offspring through postnatal day (PND) 204. Tabalumab was administered by subcutaneous injection to presumed pregnant cynomolgus monkeys (16-19 per group) every 2 weeks from gestation day (GD) 20 to 22 until parturition at doses of 0, 0. Read More

    Time Course for Onset and Recovery from Effects of a Novel Male Reproductive Toxicant: Implications for Apical Preclinical Study Designs.
    Birth Defects Res B Dev Reprod Toxicol 2015 Jun 20;104(3):91-9. Epub 2015 Jul 20.
    AstraZeneca, Mereside, Alderley Park, Alderley Edge, Macclesfield, Cheshire SK10 4TG.
    In the pharmaceutic ICH S5(R2) guidelines for reproductive toxicity testing, a premating dose duration of 14 days is considered sufficient for assessment of male fertility for compounds that are not testicular toxicants. A novel α7 subtype of nicotinic acetylcholine receptor (α7nAChR) agonist, originally intended for treatment of Alzheimer's disease, did not cause changes in sperm counts, motility, or testicular histopathology in rat toxicity studies of up to 6 months duration. However, profound decrements in male fertility (reduced pregnancy rates and litter sizes) occurred after 11 weeks of dosing in male rats. Read More

    Reproductive and Developmental Toxicity of Orally Administered Botanical Composition, UP446-Part III: Effects on Fertility and Early Embryonic Development to Implantation in Sprague Dawley Rats.
    Birth Defects Res B Dev Reprod Toxicol 2015 Aug 14;104(4):166-76. Epub 2015 Jul 14.
    Unigen, Inc, Cheonan-Si, Chungnam, Korea.
    In recent years, high prevalence of adverse effects associated to the use of traditional medicines during pregnancy is becoming alarming due to the self-medication of oral supplements by expecting mothers without supervision. Many expectant mothers use alternative and complementary medicines as a supplement to conventional pregnancy management with an inherent belief of considering herbal remedies as harmless. To the contrary, herbal remedies could incur a potential teratogenic risk both to the child bearing mother and the developing fetuses when consumed before or at the time of gestation. Read More

    Reproductive and Developmental Toxicity of Orally Administered Botanical Composition, UP446-Part II: Effects on Prenatal and Postnatal Development, Including Maternal Function in Sprague-Dawley Rats.
    Birth Defects Res B Dev Reprod Toxicol 2015 Aug 1;104(4):153-65. Epub 2015 Jun 1.
    Unigen, Inc, Seattle, Washington.
    Almost all herbal remedies could be therapeutic at one dose and toxic at another. These facts become more troubling and a double threat when uncharacterized medicinal herbs are blended together and used by expectant mothers as a supplement to conventional pregnancy management with an inherent belief of considering herbal remedies as harmless. Here we describe the potential adverse effects of UP446, a standardized bioflavonoid composition from the roots of Scutellaria baicalensis and the heartwoods of Acacia catechu, on the maternal and their first filial generation (F1) developmental and functional toxicity following exposure at doses of 250, 500, and 1000 mg/kg/day. Read More

    A Comparison of ToxCast Test Results with In Vivo and Other In Vitro Endpoints for Neuro, Endocrine, and Developmental Toxicities: A Case Study Using Endosulfan and Methidathion.
    Birth Defects Res B Dev Reprod Toxicol 2015 Apr 27;104(2):71-89. Epub 2015 May 27.
    CalEPA's Office of Environmental Health Hazard Assessment (OEHHA), Sacramento, California.
    Introduction: The U.S. Environmental Protection Agency's (EPA's) Toxicity Forecaster (ToxCast) is a potential tool for chemical prioritization, hazard identification, and risk assessment. Read More

    The Potential of Cr3 [Triaqua-μ3 -Oxo-Hexa-μ-Propionatotrichromium(III) Chloride] to Reduce Birth Defects in the Offspring of Diabetic CD-1 Mice.
    Birth Defects Res B Dev Reprod Toxicol 2015 Apr 19;104(2):65-70. Epub 2015 May 19.
    Department of Biological Sciences, The University of Alabama, Tuscaloosa, Alabama.
    Diabetes mellitus is a growing concern worldwide and leads to multiple complications during pregnancy. Pharmacologic doses of chromium (Cr) have been linked with improving insulin sensitivity and other positive benefits in the treatment of diabetes in animal models. By using streptozotocin induced hyperglycemia in female CD-1 mice, reproductive outcomes of diabetic and chromium-dosed diabetic females were examined. Read More

    Biomonitoring of the Genotoxic and Hepatotoxic Effects and Oxidative Stress Potentials of Itraconazole in Pregnant Rats.
    Birth Defects Res B Dev Reprod Toxicol 2015 Apr 27;104(2):55-64. Epub 2015 Apr 27.
    Zoology Department, Faculty of Science, Cairo University, Cairo, Egypt.
    Background: Pregnant women are more susceptible to both vaginal colonization and infection by yeast. One hundred million fungal infected patients have been treated worldwide with itraconazole (Caputo, 2003.

    Method: Itraconazole was administrated orally to pregnant rats at doses of 75, 100, or 150 mg/kg during gestational days (GD) 1 to 7 or GD 8 to 14 or GD 14 to 20. Read More

    Effects of maternal and lactational exposure to 2-hydroxy-4-methoxybenzone on development and reproductive organs in male and female rat offspring.
    Birth Defects Res B Dev Reprod Toxicol 2015 Feb;104(1):35-51
    Division of Systems Biology, National Center for Toxicological Research, Food and Drug Administration, Jefferson, Arkansas.
    Background: 2-Hydroxy-4-methoxybenzophenone (HMB) is an ultraviolet (UV) absorbing compound used in many cosmetic products as a UV-protecting agent and in plastics for preventing UV-induced photodecomposition. HMB has been detected in over 95% of randomly collected human urine samples from adults and from premature infants, and it may have estrogenic potential.

    Methods: To determine the effects of maternal and lactational exposure to HMB on development and reproductive organs of offspring, time-mated female Harlan Sprague-Dawley rats were dosed with 0, 1000, 3000, 10,000, 25,000, or 50,000 ppm HMB (seven to eight per group) added to chow from gestation day 6 until weaning on postnatal day (PND) 23. Read More

    Comparison of a modified mid-coronal sectioning technique and Wilson's technique when conducting eye and brain examinations in rabbit teratology studies.
    Birth Defects Res B Dev Reprod Toxicol 2015 Feb 21;104(1):23-34. Epub 2015 Feb 21.
    Department of Reproductive and Developmental Toxicology, GlaxoSmithKline Research & Development, King of Prussia, Pennsylvania.
    Background: There are two methods used when examining fetal rabbit eyes and brain in teratology studies. One method employs prior fixation before serial sectioning (Wilson's technique) and the other uses fresh tissue (mid-coronal sectioning).

    Methods: We modified the mid-coronal sectioning technique to include removal of eyes and brain for closer examination and to increase the number of structures that can be evaluated and compared it to the Wilson's technique. Read More

    Influence of intracellular zinc on cultures of rat cardiac neural crest cells.
    Birth Defects Res B Dev Reprod Toxicol 2015 Feb 16;104(1):11-22. Epub 2015 Feb 16.
    Department of Nutrition, University of California, Davis, California.
    Background: Developmental zinc (Zn) deficiency increases the incidence of heart anomalies in rat fetuses, in regions and structures derived from the outflow tract. Given that the development of the outflow tract requires the presence of cardiac neural crest cells (cNCC), we speculated that Zn deficiency selectively kills cNCC and could lead to heart malformations.

    Methods: Cardiac NCC were isolated from E10. Read More

    Comparative response of rat and rabbit conceptuses in vitro to inhibitors of histiotrophic nutrition.
    Birth Defects Res B Dev Reprod Toxicol 2015 Feb 4;104(1):1-10. Epub 2015 Feb 4.
    Toxicology and Environmental Research and Consulting, The Dow Chemical Company, Midland, Michigan.
    Histiotrophic nutrition via the visceral yolk sac is an essential nutritional pathway of the rodent conceptus, and inhibition of this pathway may cause growth retardation, malformations, and death in rodent embryos. Morphologic differences among species during early development indicate that the visceral yolk sac histiotrophic nutrition pathway may be of lesser importance in nonrodent species, including humans. Here, comparative studies were conducted with inhibitors of different steps in the visceral yolk sac histiotrophic nutrition pathway to determine whether the rabbit is similarly responsive to the rat. Read More

    Xenotransplantation models to study the effects of toxicants on human fetal tissues.
    Birth Defects Res B Dev Reprod Toxicol 2014 Dec 4;101(6):410-22. Epub 2014 Dec 4.
    Department of Pathology and Laboratory Medicine, Brown University, Providence, Rhode Island.
    Many diseases that manifest throughout the lifetime are influenced by factors affecting fetal development. Fetal exposure to xenobiotics, in particular, may influence the development of adult diseases. Established animal models provide systems for characterizing both developmental biology and developmental toxicology. Read More

    Negative interplay of retinoic acid and TGF-β signaling mediated by TG-interacting factor to modulate mouse embryonic palate mesenchymal-cell proliferation.
    Birth Defects Res B Dev Reprod Toxicol 2014 Dec 4;101(6):403-9. Epub 2014 Dec 4.
    Public Health College, Zhengzhou University, Zhengzhou, China; Medical College, Henan University of Science & Technology, Luoyang, China.
    Mesenchymal-cell proliferation is the main process in shelf outgrowth. Both all-trans-retinoic acid (atRA) and transforming growth factor-β3 (TGF-β3) play an important role in mouse embryonic palate mesenchymal (MEPM) cell proliferation. In the present study, we investigated the crosstalk between RA and TGF-β signaling in MEPM-cell proliferation. Read More

    Close link between protoporphyrin IX accumulation and developmental toxicity induced by N-phenylimide herbicides in rats.
    Birth Defects Res B Dev Reprod Toxicol 2014 Dec 4;101(6):429-37. Epub 2014 Dec 4.
    Environmental Health Science Laboratory, Sumitomo Chemical Co., Ltd, Konohana-ku, Osaka, Japan.
    Background: S-53482, 7-fluoro-6-[(3,4,5,6-tetrahydro)phthalimido]-4-(2-propynyl)-1,4-benzoxazin-3(2H)-one (flumioxazin), is an N-phenylimide herbicide and developmentally toxic to rats, but not to rabbits. The day of greatest sensitivity to S-53482 is gestational day (GD) 12 in rats. There is a compound-specific difference in developmental toxicity among structurally similar compounds including S-23121 (N-[4-chloro-2-fluoro-5-[(1-methyl-2-propynyl)oxy]phenyl]-3,4,5,6-tetrahydrophthalimide; teratogenic) and S-23031 (pentyl 2-chloro-4-fluoro-5-(3,4,5,6-tetrahydrophthalimido)phenoxyacetate (flumiclorac pentyl); nonteratogenic). Read More

    1 OF 11