The purpose of this journal is to publish original contributions describing the toxicity of chemicals to developing organisms and the process of reproduction. The scope of the journal will inlcude:    • toxicity of new chemical entities and biotechnology derived products to developing organismal systems;  • toxicity of these and other xenobiotic agents to reproductive function;  • multi-generation studies;  • endocrine-mediated toxicity, particularly for endpoints that are relevant to development and reproduction;  • novel protocols for evaluating developmental and reproductive toxicity;    Part B: Developmental and Reproductive Toxicology , formerly published as Teratogenesis, Carcinogenesis and Mutagenesis

The purpose of this journal is to publish original research contributions that describe the toxicity of chemicals to developing organisms and the reproductive process. The scope of the journal includes: • The toxicity of new chemical entities and biotechnology-derived products to developing organismal systems; • The toxicity of these and other xenobiotic agents to reproductive function; • Multi-generation studies; • Endocrine-mediated toxicity, particularly for endpoints relevant to development and reproduction; • Novel protocols for evaluating developmental and reproductive toxicity. Part B: Developmental and Reproductive Toxicology, formerly published as Teratogenesis, Carcinogenesis and Mutagenesis.

本期刊旨在发表关于化学物质对发育生物体毒性的原创研究。期刊的范围包括：• 新化学实体和生物技术衍生产品对发育生物系统的毒性；• 这些及其他外源性物质对生殖功能的毒性；• 多代研究；• 内分泌介导的毒性，特别是与发育和生殖相关的终点；• 评估发育和生殖毒性的创新协议。Part B: Developmental and Reproductive Toxicology，前身为《Teratogenesis, Carcinogenesis and Mutagenesis》。

Birth Defects Research Part B - Developmental and Reproductive Toxicology

BACKGROUND
Cu deficiency results in embryonic defects and yolk sac (YS) vasculature abnormalities. In diverse model systems, Cu treatment modulates angiogenesis, perhaps by influencing the activity of angiogenic mediators such as vascular endothelial growth factor (VEGF). Conversely, Cu chelators can suppress angiogenesis.


METHODS
Gestation day (GD) 8.5 embryos from mice fed Cu-adequate (Cu+) or Cu-deficient (Cu-) diets were cultured in Cu+ or Cu- medium for 48 hr. Growth and development were evaluated, and YS vessel diameters were measured. Using RT-PCR and immunohistochemistry, the mRNA and protein expressions of VEGF, Flt-1, Flk-1, Angiopoietin-1 (Ang-1), and Tie-2 were analyzed.


RESULTS
Cu+/Cu+ embryos developed normally, whereas Cu-/Cu- embryos showed a high incidence of developmental anomalies. Cu-/Cu- YS had a high proportion of vessels that were large in diameter compared to the Cu+/Cu+ YS. The mRNA expression of angiogenic mediators in Cu-/Cu- YS was similar to that in Cu+/Cu+ YS. The protein expression of VEGF in the Cu-/Cu- YS without any vessel defects, and Tie-2 in the Cu-/Cu- YS with both vessel defects and blood islands was significantly lower than that in the Cu+/Cu+ YS. The protein expression of Flt-1, Flk-1 and Ang-1 was similar among groups regardless of the presence, or type, of vessel defects.


CONCLUSIONS
Results from the current study support the concept that Cu is required for the normal development of YS vasculature. Our data suggest that the impaired vascularization of Cu-deficient YS cannot be explained fully by the altered protein expression of the angiogenic growth factors reported here.

Soo Jin Yang

Janet Y. Uriu-Adams

Carl L. Keen

Robert B. Rucker

Louise Lanoue

Birth Defects Research Part B: Developmental and Reproductive Toxicology

Birth Defect Res B

Effects of copper deficiency on mouse yolk sac vasculature and expression of angiogenic mediators

铜缺乏对小鼠卵黄囊血管及促血管生成介质表达的影响

Atrazine, a chlorotriazine herbicide, is used to control annual grasses and broadleaf weeds. In this review, we summarize our laboratory's work evaluating the neuroendocrine toxicity of atrazine (and related chlorotriazines) from an historic perspective. We provide the rationale for our work as we have endeavored to determine: 1) the underlying reproductive changes leading to the development of mammary gland tumors in the atrazine‐exposed female rat; 2) the cascade of physiological events that are responsible for these changes (i.e., the mode of action for mammary tumors); 3) the potential cellular mechanisms involving adverse effects of atrazine; and 4) the range of reproductive alterations associated with this pesticide.Birth Defects Res (Part B), 2007. Published 2007 Wiley‐Liss, Inc.

Ralph L. Cooper

Susan C. Laws

Parikshit C. Das

Michael G. Narotsky

Jerome M. Goldman

E. Lee Tyrey

Tammy E. Stoker

Birth Defects Research Pt B

Atrazine and reproductive function: mode and mechanism of action studies

阿特拉津与生殖功能：作用模式与机制研究

Congenital eye and craniofacial anomalies are associated with the dysregulation of retinoic acid (RA) levels during embryogenesis. In the present study, we observed that RA and pitx2a cooperatively regulate early cranial neural crest migration from the rhombencephalon to the pharyngeal arches and from the mesencephalon and prosencephalon to the periocular mesenchyme and frontonasal processes. The cranial neural crest tracked toward areas of high RA activity (i.e., developing eye) and circumvented areas of low RA activity (i.e., mesencephalon). Although previous studies have shown that RA increased pitx2a expression at later stages of cranial neural crest development, in these studies we found that RA inhibited pitx2a expression in the early migrating ventral cranial neural crest. Increased RA or decreased Pitx2a expression decreased cell survival and inhibited ventral neural crest migration. Decreased RA or increased pitx2a expression markedly disrupted both dorsal and ventral neural crest migration. The tight control of RA and subsequent regulation of pitx2 were required for precise cranial neural crest survival and migration. These alterations in the neural crest in the periocular mesenchyme and frontonasal processes may reflect the craniofacial dysmorphism and microphthalmia observed in cases of increased (i.e., as resulting from isoretinoin exposure) or decreased (i.e., as may occur in fetal alcohol syndrome) RA signaling during pregnancy

Bahaar Chawla

Elisa Schley

Antionette L. Williams

Brenda L. Bohnsack

Birth Defects Res B

Retinoic Acid and Pitx2 Regulate Early Neural Crest Survival and Migration in Craniofacial and Ocular Development

视黄酸和Pitx2调控早期神经嵴存活和迁移在颅面和眼发育中的作用

Hyperthermia has been known to induce malformations in numerous animal models as well being associated with human abnormalities. This was apparent particularly when the hyperthermia exposure was during the early stages of neural development. Although it was recognized relatively early that these exposures induced cell death, the specific molecular mechanism of how a brief heat exposure was translated in to specific cellular functions remains largely unknown. While our understanding of the events that govern how cells react to heat, or stresses in general, has increased, there is much that remains undiscovered. In this brief review, animal and clinical observations are outlined as are some of the scientific explorations that were undertaken to characterize, define, and better understand the morphological, biochemical, and molecular effects of hyperthermia on the developing embryo.

Gregory D. Bennett

Hyperthermia: malformations to chaperones

高温：从畸形到伴侣蛋白

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. The juvenile period is particularly vulnerable to environmental agent, therefore, we evaluated the effects of a 28-day exposure to ATR on the dopaminergic system in pubertal rats. Sprague-Dawley rats were treated orally with ATR at 50, 100, and 200 mg/kg bw, daily from postnatal days 27 to 54. In this study, we examined the hypothesis that pubertal exposure to ATR would disrupt the development of the nigrostriatal dopamine (DA) system. The content of DA and levodopa (L-DA) were examined in striatum samples by HPLC-FL, and the mRNA and protein expression of tyrosine hydroxylase, orphan nuclear hormone receptor (Nurr1), Nurr1 interacting protein (NuIP), and cyclin-dependent kinase inhibitors of the Cip̲Kip family (p57kip2) were examined in samples of the nigrostriatum by use of fluorescence Real-Time quantitative polymerase chain reaction (PCR). Exposure of juvenile rats to the high dose of ATR led to reduced levels of DA and L-DA, genes expression of NuIP, Nurr1, and p57kip2 in animals.

Yan-Shu Li

Xi He

Kun Ma

Yan-Ping Wu

Bai-Xiang Li

The Effect of Exposure to Atrazine on Dopaminergic Development in Pubertal Male SD Rats

暴露于莠去津对青春期雄性SD大鼠多巴胺能发育的影响

Publication Information	Publisher: Wiley-Liss Inc.，Publishing cycle: Bimonthly，Journal Type: journal，Open Access Journals: No
Basic data	Year of publication: 2003，Proportion of original research papers: 0.00%，Self Citation Rate:N.A.， Gold OA Rate: 0.00%
Average review cycle	网友分享经验：>12周，或约稿
Average recruitment ratio	网友分享经验：较易

Birth Defects Research Part B - Developmental and Reproductive Toxicology

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Effects of copper deficiency on mouse yolk sac vasculature and expression of angiogenic mediators

Atrazine and reproductive function: mode and mechanism of action studies

Retinoic Acid and Pitx2 Regulate Early Neural Crest Survival and Migration in Craniofacial and Ocular Development

Hyperthermia: malformations to chaperones

The Effect of Exposure to Atrazine on Dopaminergic Development in Pubertal Male SD Rats

Retinoic Acid and Pitx2 Regulate Early Neural Crest Survival and Migration in Craniofacial and Ocular Development

The Effect of Exposure to Atrazine on Dopaminergic Development in Pubertal Male SD Rats

Hyperthermia: malformations to chaperones

Atrazine and reproductive function: mode and mechanism of action studies

Effects of copper deficiency on mouse yolk sac vasculature and expression of angiogenic mediators