Birth Defects Research Part B: Developmental and Reproductive Toxicology This is an RSS file. You can use it to subscribe to this data in your favourite RSS reader or to display this data on your own website or blog.

Embryo‐Fetal Developmental Toxicity Studies with Pregabalin in Mice and Rabbits
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. Pregabalin administration to mice did not induce maternal or developmental toxicity at doses up to 2500 mg/kg, which was associated with a maternal plasma exposure (AUC0–24) of 3790 μg•hr/ml, ≥30 times the expected human...
Source: Birth Defects Research Part B: Developmental and Reproductive Toxicology - January 31, 2016 Category: Perinatology & Neonatology Authors: Dennis C. Morse Tags: Original Article Source Type: research

A Probability Analysis of Historical Pregnancy and Fetal Data from Dutch Belted and New Zealand White Rabbit Strains from Embryo–Fetal Development Studies
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. A probability analysis was conducted on 2014 HCD col...
Source: Birth Defects Research Part B: Developmental and Reproductive Toxicology - January 31, 2016 Category: Perinatology & Neonatology Authors: Lorraine M. Posobiec, Estella M. Cox, Howard M. Solomon, Elise M. Lewis, Kai‐fen Wang, Dinesh Stanislaus Tags: Research Article Source Type: research

A Developmental Toxicology Assay Platform for Screening Teratogenic Liability of Pharmaceutical Compounds
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. Individually, the assays presented good (73–82%) predictivity. However, it remains to be determined whether combining or tiering the assays co...
Source: Birth Defects Research Part B: Developmental and Reproductive Toxicology - January 5, 2016 Category: Perinatology & Neonatology Authors: Karen Augustine‐Rauch, Cindy X. Zhang, Julieta M. Panzica‐Kelly Tags: Research Article Source Type: research

Advanced Paternal Age and Risk of Musculoskeletal Congenital Anomalies in Offspring
CONCLUSIONSA slightly higher risk for overall musculoskeletal CAs in offspring was found with increasing paternal age, mainly due to an excess risk of syndromic musculoskeletal CAs for fathers aged 40+ years. While associations between paternal age 50+ years and increased risk of all subtypes of musculoskeletal CAs were indicated, advanced paternal age likely plays a minor role in the etiology of these anomalies (Source: Birth Defects Research Part B: Developmental and Reproductive Toxicology)
Source: Birth Defects Research Part B: Developmental and Reproductive Toxicology - December 10, 2015 Category: Perinatology & Neonatology Authors: Stine Kjaer Urhoj, Laust Hvas Mortensen, Anne‐Marie Nybo Andersen Tags: Research Article Source Type: research

Mechanism of Developmental Effects in Rats Caused by an N‐Phenylimide Herbicide: Transient Fetal Anemia and Sequelae during Mid‐to‐Late Gestation
ConclusionWe propose that developmental toxicity results from PPO inhibition in primitive erythroblasts, causing transient fetal anemia followed by death. Compensatory enlargement of the fetal heart results in failure of interventricular foramen closure and VSD. Reduced serum protein leads to delayed ossification and wavy ribs (Source: Birth Defects Research Part B: Developmental and Reproductive Toxicology)
Source: Birth Defects Research Part B: Developmental and Reproductive Toxicology - December 1, 2015 Category: Perinatology & Neonatology Authors: Satoshi Kawamura, Takafumi Yoshioka, Nobuaki Mito, Noriyuki Kishimoto, Masanao Nakaoka, Alan G. Fantel Tags: Research Article Source Type: research

Numeric Estimates of Teratogenic Severity from Embryo–Fetal Developmental Toxicity Studies
A developing organism exposed to a toxicant will have a response that ranges from none to severe (i.e., death or malformation). The response at a given dosage may be termed teratogenic (or developmental toxic) severity and is dependent on exposure conditions. Prenatal/embryo–fetal developmental (EFD) toxicity studies in rodents and rabbits are the most consistent and definitive assessments of teratogenic severity, and teratogenesis screening assays are best validated against their results. A formula is presented that estimates teratogenic severity for each group, including control, within an EFD study. The developmental ...
Source: Birth Defects Research Part B: Developmental and Reproductive Toxicology - December 1, 2015 Category: Perinatology & Neonatology Authors: L. David Wise Tags: Original Article Source Type: research

Investigation on Toxicity and Teratogenicity in Rats of a Retinoid‐Polyamine Conjugate with Potent Anti‐Inflammatory Properties
Previous studies have shown that N1,N12‐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 induc...
Source: Birth Defects Research Part B: Developmental and Reproductive Toxicology - December 1, 2015 Category: Perinatology & Neonatology Authors: Theodoros Petridis, Dimitra Giannakopoulou, Vassiliki Stamatopoulou, Katerina Grafanaki, Christos G. Kostopoulos, Helen Papadaki, Christina J. Malavaki, Nikos K. Karamanos, Stathianna Douroumi, Dionysios Papachristou, George E. Magoulas, Dionissios Papaio Tags: Research Article Source Type: research

Diabetes in the Cohen Rat Intensifies the Fetal Pancreatic Damage Induced by the Diabetogenic High Sucrose Low Copper Diet
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. However, oxidative stress was observed in the placenta and term fetal liver of diabetic and nondiabetic controls. We now investigated whether the fetal pancreas is affected by this diet and whether the effects result from oxidative stress, maternal hyperglycemia,...
Source: Birth Defects Research Part B: Developmental and Reproductive Toxicology - December 1, 2015 Category: Perinatology & Neonatology Authors: Zivanit Ergaz, Meytal Neeman‐azulay, Liza Weinstein‐Fudim, Sarah Weksler‐Zangen, Dana Shoshani‐Dror, Moshe Szyf, Asher Ornoy Tags: Research 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 - December 1, 2015 Category: Perinatology & Neonatology Tags: Issue Information Source Type: research

Visualizing Compound Distribution during Zebrafish Embryo Development: The Effects of Lipophilicity and DMSO
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 –4.63), Giemsa stain (logP –0.77), Van Gierson stain (logP 1.64), Cresyl fast violet (logP 3.5), Eosine Y (logP 4.8...
Source: Birth Defects Research Part B: Developmental and Reproductive Toxicology - October 1, 2015 Category: Perinatology & Neonatology Authors: Coco Koning, Manon Beekhuijzen, Marysia Tobor‐Kapłon, Selinda Vries‐Buitenweg, Dick Schoutsen, Nico Leeijen, Beppy Waart, Harry Emmen Tags: Research Article Source Type: research

Early Vaginal Opening in Juvenile Female Rats Given BRAF‐Inhibitor Dabrafenib Is Not Associated with Early Physiologic Sexual Maturation
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. An investigative study was conducted that mimicked the definitive study design, with rats given DAB or vehicle orally from Postnatal Day (PND) 7 to 35 and with necropsy subsets just before VO, at the first and second estrus, along with ...
Source: Birth Defects Research Part B: Developmental and Reproductive Toxicology - October 1, 2015 Category: Perinatology & Neonatology Authors: Lorraine M. Posobiec, Justin D. Vidal, Angela Hughes‐Earle, Susan B. Laffan, Timothy Hart Tags: Research Article Source Type: research

Exposure Duration‐Dependent Ovarian Recovery in Methoxychlor‐Treated Mice
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. The current study was undertaken to determine whether MXC treatment for 20 days results in reduced antral follicle numbers and fertility at 30 and 60 days after dosing. To test this hypothesis, adult CD‐1 female mice were dosed wi...
Source: Birth Defects Research Part B: Developmental and Reproductive Toxicology - October 1, 2015 Category: Perinatology & Neonatology Authors: Lawrence V. Tannenbaum, Jodi A. Flaws 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 - August 25, 2015 Category: Perinatology & Neonatology Tags: Issue Information Source Type: research

Effect of Age, Duration of Exposure, and Dose of Atrazine on Sexual Maturation and the Luteinizing Hormone Surge in the Female Sprague–Dawley Rat
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. Slight reductions in fertility and the percentage of F1 generation pups surviving to PND 21 in the gestationally e...
Source: Birth Defects Research Part B: Developmental and Reproductive Toxicology - August 1, 2015 Category: Perinatology & Neonatology Authors: Charles B. Breckenridge, Pragati Sawhney Coder, Merrill O. Tisdel, James W. Simpkins, Kun Don Yi, Chad D. Foradori, Robert J. Handa Tags: Original Article Source Type: research