Excessive Retinoic Acid Impaired Proliferation and Differentiation of Human Fetal Palatal Chondrocytes (hFPCs)
Chondrocyte proliferation and differentiation is a fundamental process during hard palatogenesis. Excessive retinoic acid (RA), the biologically most active metabolite of vitamin A, has been reported to adversely affect chondrogenesis. The aim of this study was to investigate the mechanisms underlying RA‐induced chondrocyte differentiation by using human fetal palatal chondrocytes (hFPCs) aging about 9 weeks of amenorrhea. RA treatment inhibited proliferation and induced apoptosis in hFPCs. Alkaline phosphatase activity assay, quantitative alcian blue staining, and real‐time PCR analysis revealed that RA treatment stim...
Source: Birth Defects Research Part B: Developmental and Reproductive Toxicology - May 2, 2014 Category: Perinatology & Neonatology Authors: Ning Li, Yusheng Xu, Huanhuan Zhang, Liyun Gao, Jue Li, Yongchao Wang, Zhan Gao, Xinjuan Pan, Xiaozhuan Liu, Xing Li, Zengli Yu Tags: Research Article Source Type: research

Effects of Ethylene Glycol Monomethyl Ether and Its Metabolite, 2‐Methoxyacetic Acid, on Organogenesis Stage Mouse Limbs In Vitro
Exposure to ethylene glycol monomethyl ether (EGME), a glycol ether compound found in numerous industrial products, or to its active metabolite, 2‐methoxyacetic acid (2‐MAA), increases the incidence of developmental defects. Using an in vitro limb bud culture system, we tested the hypothesis that the effects of EGME on limb development are mediated by 2‐MAA‐induced alterations in acetylation programming. Murine gestation day 12 embryonic forelimbs were exposed to 3, 10, or 30 mM EGME or 2‐MAA in culture for 6 days to examine effects on limb morphology; limbs were cultured for 1 to 24 hr to monitor effects on the ...
Source: Birth Defects Research Part B: Developmental and Reproductive Toxicology - May 2, 2014 Category: Perinatology & Neonatology Authors: Caroline Dayan, Barbara F. Hales Tags: Research Article Source Type: research

Atrazine and Pregnancy Outcomes: A Systematic Review of Epidemiologic Evidence
Atrazine (ATR) is a commonly used agricultural herbicide that has been the subject of epidemiologic studies assessing its relation to reproductive health problems. This review evaluates both the consistency and the quality of epidemiologic evidence testing the hypothesis that ATR exposure, at usually encountered levels, is a risk factor for birth defects, small for gestational age birth weight, prematurity, miscarriages, and problems of fetal growth and development. We followed the current methodological guidelines for systematic reviews by using two independent researchers to identify, retrieve, and evaluate the relevant ...
Source: Birth Defects Research Part B: Developmental and Reproductive Toxicology - May 2, 2014 Category: Perinatology & Neonatology Authors: Michael Goodman, Jack S. Mandel, John M. DeSesso, Anthony R. Scialli Tags: Review Article Source Type: research

Multigeneration Reproduction and Male Developmental Toxicity Studies on Atrazine in Rats
CONCLUSIONSDietary administration of ATR did not affect rat reproduction up to a parentally toxic dose of 38.7 mg/kg/day. Some effects on male reproductive system development occurred after high dose, bolus administration to dams, but doses were much higher than expected under normal use conditions. Thus, oral RfDs for ATR would be protective for reproductive effects (Source: Birth Defects Research Part B: Developmental and Reproductive Toxicology)
Source: Birth Defects Research Part B: Developmental and Reproductive Toxicology - May 2, 2014 Category: Perinatology & Neonatology Authors: John M. DeSesso, Anthony R. Scialli, Tacey E. K. White, Charles B. Breckenridge Tags: Research Article Source Type: research

Effects of Macrolide Antibiotics on Rat Embryonic Heart Function In Vitro
The Swedish Medical Product Agency (MPA) has listed erythromycin as a suggested human teratogen, causing cardiovascular malformations. It is further suggested that this may be a class effect of macrolide antibiotics. The proposed teratogenic mechanism is blockade of the human ether‐á‐go‐go‐related (hERG)/IKr current in the embryonic heart causing bradycardia and arrhythmia resulting in altered cardiac blood flow and/or embryonic hypoxia. To test this hypothesis, we examined the effect of three macrolide antibiotics on the function of the rat embryonic heart. Gestational day 13 rat embryos in vitro were exposed to ...
Source: Birth Defects Research Part B: Developmental and Reproductive Toxicology - April 17, 2014 Category: Perinatology & Neonatology Authors: Mats F. Nilsson, William S. Webster Tags: Research Article Source Type: research

Placental Transfer of a Fully Human IgG2 Monoclonal Antibody in the Cynomolgus Monkey, Rat, and Rabbit: A Comparative Assessment from during Organogenesis to Late Gestation
Understanding species differences in the placental transfer of monoclonal antibodies is important to inform species selection for nonclinical safety assessment, interpret embryo‐fetal changes observed in these studies, and extrapolate their human relevance. Data presented here for a fully human immunoglobulin G2 monoclonal antibody (IgG2X) revealed that, during organogenesis, in both the cynomolgus monkey (gestation day 35 [gd35]) and the rat (gd10) the extent of IgG2X placental transfer (approximately 0.5% maternal plasma concentration, MPC) was similar to the limited published human data for endogenous IgG. At this ear...
Source: Birth Defects Research Part B: Developmental and Reproductive Toxicology - April 17, 2014 Category: Perinatology & Neonatology Authors: Graeme J. Moffat, Marc W. Retter, Gayle Kwon, Mark Loomis, M. Benjamin Hock, Colin Hall, Jeanine Bussiere, Elise M. Lewis, Gary J. Chellman Tags: Research Article Source Type: research

Dose‐Dependent Effects and Reversibility of the Injuries Caused by Nandrolone Decanoate in Uterine Tissue and Fertility of Rats
This study is the first to investigate the effects of different doses of nandrolone decanoate (ND) upon uterine tissue and fertility, and if the reproductive alterations can be restored after cessation of the treatment. Wistar female rats were treated with ND at doses of 1.87, 3.75, 7.5, and 15 mg/kg body weight, diluted in vehicle (n = 30/group), or received only mineral oil (control group, n = 45). The animals were divided into three periods of study: ND‐treated receiving a daily subcutaneous injection for 15 consecutive days (1), and treatment with ND followed by 30‐day recovery (2), and 60‐day recovery (3). At t...
Source: Birth Defects Research Part B: Developmental and Reproductive Toxicology - April 17, 2014 Category: Perinatology & Neonatology Authors: Larissa Berloffa Belardin, Vinícius Augusto Simão, Gabriel Adan Araújo Leite, Luiz Gustavo de Almeida Chuffa, Isabel Cristina Cherici Camargo Tags: Original Article Source Type: research

Dermal Developmental Toxicity of N‐Phenylimide Herbicides in Rats
ConclusionsBased on the results, S‐53482 and S‐23121 were teratogenic when administered dermally to pregnant rats as were the compounds administered orally. Thus, investigation of the mechanism and its human relevancy become more important. (Source: Birth Defects Research Part B: Developmental and Reproductive Toxicology)
Source: Birth Defects Research Part B: Developmental and Reproductive Toxicology - April 17, 2014 Category: Perinatology & Neonatology Authors: Satoshi Kawamura, Terushige Kato, Masanao Nakaoka, Alan G. Fantel Tags: Original Article Source Type: research

The Novel Use of a Heterozygous Knockout Mouse for Embryofetal Development Assessment of a Glucokinase Activator
In this study, the gkdel/wt mouse was used as an alternative rodent strain for embryofetal development studies with AZD1656. Heterozygous global knockout gkdel/wt females were dosed with 20, 50, or 130 mg/kg/day of AZD1656 or vehicle for a minimum of 14 consecutive days before mating with wild‐type males and throughout organogenesis. Maternal effects were confined to slightly reduced food consumption, reduced body weight gain, and the pharmacologic effect of decreased plasma glucose. Fetuses were genotyped. Fetal weights at the high dose were slightly reduced but there was no effect on fetal survival. There were two spec...
Source: Birth Defects Research Part B: Developmental and Reproductive Toxicology - April 17, 2014 Category: Perinatology & Neonatology Authors: Terri Mitchard, Jane Stewart Tags: Research Article Source Type: research

Treatment of Mid‐Pregnant Mice with KRN633, an Inhibitor of Vascular Endothelial Growth Factor Receptor Tyrosine Kinase, Induces Abnormal Retinal Vascular Patterning in Their Newborn Pups
In this study, we examined how the treatment of mid‐pregnant mice with KRN633 affects the development and morphology of vascular components (endothelial cells, pericytes, and basement membrane) in the retinas of their newborn pups. Pregnant mice were treated with KRN633 (5 mg/kg) once daily from embryonic day 13.5 until the day of delivery. Vascular components were examined using immunohistochemistry with specific markers for each component. Radial vascular growth in the retina was slightly delayed until postnatal day 4 (P4) in the newborn pups of KRN633‐treated mothers. On P8, compared with the pups of control mothers...
Source: Birth Defects Research Part B: Developmental and Reproductive Toxicology - April 1, 2014 Category: Perinatology & Neonatology Authors: Akane Morita, Tsutomu Nakahara, Naomichi Abe, Yuki Kurauchi, Asami Mori, Kenji Sakamoto, Tohru Nagamitsu, Kunio Ishii Tags: Research Article Source Type: research

Developmental Toxicity Studies with Atrazine and its Major Metabolites in Rats and Rabbits
Atrazine (ATR), hydroxyatrazine (OH‐ATR), and the three chloro metabolites of ATR (deethylatrazine [DEA], deisopropylatrazine [DIA], diaminochlorotriazine [DACT]) were evaluated for developmental effects in rats and rabbits. Three developmental toxicity studies were conducted on ATR in rats (two studies) and rabbits and a developmental toxicity study was conducted in rats for each of the four ATR metabolites DEA, DIA, DACT, and OH‐ATZ. ATR administration by gavage to pregnant rats and rabbits from implantation (gestation day [GD] 6 in rat, GD 7 in rabbit) through closure of the palate (GD 15 in rat and GD 19 in rabbit)...
Source: Birth Defects Research Part B: Developmental and Reproductive Toxicology - April 1, 2014 Category: Perinatology & Neonatology Authors: Anthony R. Scialli, John M. DeSesso, Charles B. Breckenridge Tags: Original Article Source Type: research

Issue Information
(Source: Birth Defects Research Part B: Developmental and Reproductive Toxicology)
Source: Birth Defects Research Part B: Developmental and Reproductive Toxicology - April 1, 2014 Category: Perinatology & Neonatology Tags: Issue Information Source Type: research

4‐O‐methylhonokiol Inhibits Serious Embryo Anomalies Caused by Nicotine via Modulations of Oxidative Stress, Apoptosis, and Inflammation
CONCLUSIONSThese findings indicate that 4‐O‐methylhonokiol reduces serious embryo anomalies caused by nicotine in mouse embryos via the modulations of oxidative stress, apoptosis, and inflammation, suggesting that 4‐O‐methylhonokiol may be a preventive and therapeutic agent against the dysmorphology induced by maternal smoking during pregnancy. (Source: Birth Defects Research Part B: Developmental and Reproductive Toxicology)
Source: Birth Defects Research Part B: Developmental and Reproductive Toxicology - April 1, 2014 Category: Perinatology & Neonatology Authors: Chunmei Lin, Jung‐Min Yon, Jin Tae Hong, Jong Kwon Lee, Jayoung Jeong, In‐Jeoung Baek, Beom Jun Lee, Young Won Yun, Sang‐Yoon Nam Tags: Research Article Source Type: research

Embryofetal Development Study of Vismodegib, a Hedgehog Pathway Inhibitor, in Rats
Vismodegib (Erivedge) is a first‐in‐class small‐molecule hedgehog pathway inhibitor for the treatment of adults with advanced basal‐cell carcinoma. Because this pathway is known to play key roles in patterning and growth during vertebrate development, vismodegib was anticipated to be embryotoxic. To support marketing applications, an embryofetal development study was completed in which a limited number of pregnant rats (n = 6/group) was administered vismodegib by oral gavage on gestation days 6 to 17. When vismodegib was administered at ≥60 mg/kg/day, doses associated with evidence of pharmacologic activity in pr...
Source: Birth Defects Research Part B: Developmental and Reproductive Toxicology - April 1, 2014 Category: Perinatology & Neonatology Authors: Eric Morinello, Michael Pignatello, Loris Villabruna, Petra Goelzer, Heinrich Bürgin Tags: Research Article Source Type: research

Key Learnings from Performance of the U.S. EPA Endocrine Disruptor Screening Program (EDSP) Tier 1 In Vitro Assays
This article examines the procedures, results, and data interpretation for the five Tier 1 in vitro assays: estrogen receptor (ER) and androgen receptor binding assays, an ER transactivation assay, an aromatase assay, and a steroidogenesis assay. Data are presented from two laboratories that have evaluated approximately 11 compounds in the Tier 1 in vitro assays. Generally, the ER and androgen receptor binding assays and the aromatase assay showed good specificity and reproducibility. As described in the guideline for the ER transactivation assay, a result is considered positive when the test compound induces a reporter ge...
Source: Birth Defects Research Part B: Developmental and Reproductive Toxicology - February 10, 2014 Category: Perinatology & Neonatology Authors: Matthew J. LeBaron, Katie K. Coady, John C. O'Connor, Diane L. Nabb, Lauren K. Markell, Suzanne Snajdr, M. Sue Marty Tags: Research Article Source Type: research