Birth defects research. Part B, Developmental and reproductive toxicology最新文献_第7页

Reproductive and developmental toxicity of solvents and gases 溶剂和气体的生殖和发育毒性

Birth defects research. Part B, Developmental and reproductive toxicology Pub Date : 2022-01-01 DOI: 10.1016/B978-0-12-804239-7.00021-4

S. Vulimiri, M. Pratt, Shaila Kulkarni, S. Beedanagari, B. Mahadevan

引用次数: 9

Alternative methods to animal experimentation for testing developmental toxicity 动物实验测试发育毒性的替代方法

Birth defects research. Part B, Developmental and reproductive toxicology Pub Date : 2022-01-01 DOI: 10.1016/b978-0-323-89773-0.00007-2

D. Pamies, Carmen Estevan, E. Vilanova, M. Sogorb

引用次数: 0

Embryonic and fetal toxic lesions and stem cell therapy 胚胎和胎儿毒性病变和干细胞治疗

Birth defects research. Part B, Developmental and reproductive toxicology Pub Date : 2022-01-01 DOI: 10.1016/b978-0-323-89773-0.00052-7

V. B. Popov, G. Protasova, L. V. Shabasheva, N. S. Khlebnikova

引用次数: 0

Endocrine disruption 内分泌干扰

Birth defects research. Part B, Developmental and reproductive toxicology Pub Date : 2022-01-01 DOI: 10.1016/b978-0-323-89773-0.00058-8

Timothy J. Evans

引用次数: 0

Developmental toxicity studies of lumefantrine and artemether in rats and rabbits 苯甲醚和甲醚对大鼠和家兔的发育毒性研究

Birth defects research. Part B, Developmental and reproductive toxicology Pub Date : 2016-12-29 DOI: 10.1002/bdrb.21189

Robert L. Clark, Maureen Youreneff, Anthony M. DeLise

{"title":"Developmental toxicity studies of lumefantrine and artemether in rats and rabbits","authors":"Robert L. Clark, Maureen Youreneff, Anthony M. DeLise","doi":"10.1002/bdrb.21189","DOIUrl":"10.1002/bdrb.21189","url":null,"abstract":"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. This report describes the results of embryo-fetal development studies of artemether alone, lumefantrine alone, and the combination in rats and rabbits as well as toxicokinetic studies of lumefantrine in pregnant rabbits. The developmental no-effect levels for lumefantrine were 300 mg/kg/day in rats (based on a 25% decrease in litter size at 1000 mg/kg/day) and 1000 mg/kg/day in rabbits. The calculated safety margins based on human equivalent dose and plasma Cmax and AUC values were in the range of 2.5- to 17-fold. The developmental no-effect levels for artemether were 3 mg/kg/day in rats and 25 mg/kg/day in rabbits. Lumefantrine caused no teratogenicity and was not a potent embryotoxin in rats and rabbits. Expected artemisinin-like findings were seen with artemether alone and with artemether/lumefantrine combined except that no malformations were observed. There were no findings in pregnant rats and rabbits that would cause increased concern for the use of artemether–lumefantrine in the first trimester compared to other ACTs.","PeriodicalId":9120,"journal":{"name":"Birth defects research. Part B, Developmental and reproductive toxicology","volume":"107 6","pages":"243-257"},"PeriodicalIF":0.0,"publicationDate":"2016-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/bdrb.21189","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81269597","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 8

Lost in translation: The search for an in vitro screen for spermatogenic toxicity 迷失在翻译中:寻找一种体外筛选精子毒性

Birth defects research. Part B, Developmental and reproductive toxicology Pub Date : 2016-12-26 DOI: 10.1002/bdrb.21188

Robert E. Chapin, Timothy Winton, William Nowland, Nichole Danis, Steven Kumpf, Kjell Johnson, Aleasha Coburn, Jan-Bernd Stukenborg

{"title":"Lost in translation: The search for an in vitro screen for spermatogenic toxicity","authors":"Robert E. Chapin, Timothy Winton, William Nowland, Nichole Danis, Steven Kumpf, Kjell Johnson, Aleasha Coburn, Jan-Bernd Stukenborg","doi":"10.1002/bdrb.21188","DOIUrl":"10.1002/bdrb.21188","url":null,"abstract":"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. A peripheral torus-shaped zone in these explants would often contain tubules showing spermatogenesis, while the middle of each chunk was often necrotic, depending on the thickness of the tissue. The endpoint was histology: what proportion of tubules in the “permissive torus” actually contained healthy pachytene spermatocytes or spermatids? Extensive statistical modeling revealed that a useful predictive model required more than 60% of these tubules to show spermatogenesis. Separately, the logistics of running this as a predictive assay require that the controls consistently produce ≥ 60% tubules with pachytenes and round spermatids, and achieving this level of spermatogenesis reliably and consistently every week proved ultimately not possible. Extensive trials with various media additions and amendments proved incapable of maintaining the frequency of spermatogenic tubules at consistently ≥ 60%. Congruent with Schooler's “decline effect”; generally, the more often we ran these cultures, the worse the performance became. We hope that future efforts in this area may use our experience as a starting point on the way to a fully productive in vitro model of spermatogenesis.","PeriodicalId":9120,"journal":{"name":"Birth defects research. Part B, Developmental and reproductive toxicology","volume":"107 6","pages":"225-242"},"PeriodicalIF":0.0,"publicationDate":"2016-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/bdrb.21188","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80537605","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 20

Exposure to high-concentration oxygen in the neonatal period induces abnormal retinal vascular patterning in mice 暴露于高浓度氧在新生期诱导小鼠视网膜血管异常模式

Birth defects research. Part B, Developmental and reproductive toxicology Pub Date : 2016-10-28 DOI: 10.1002/bdrb.21187

Akane Morita, Hiroko Ushikubo, Asami Mori, Kenji Sakamoto, Tsutomu Nakahara

{"title":"Exposure to high-concentration oxygen in the neonatal period induces abnormal retinal vascular patterning in mice","authors":"Akane Morita, Hiroko Ushikubo, Asami Mori, Kenji Sakamoto, Tsutomu Nakahara","doi":"10.1002/bdrb.21187","DOIUrl":"10.1002/bdrb.21187","url":null,"abstract":"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. The present study aimed to determine (1) whether vascular abnormalities are observed in the retina of newborn mice exposed to high concentrations of oxygen, and (2) how astrocyte network formation is affected following the exposure to hyperoxia. Newborn (postnatal day 0) mice were exposed to 75% oxygen for 48 or 96 hr. During hyperoxia exposure, VEGF expression decreased, and the onset of retinal vascularization was completely suppressed. After completion of the hyperoxic period, retinal vascularization occurred, but it was delayed in a hyperoxic exposure duration-dependent manner. In retinas of hyperoxia-exposed mice, dense capillary plexuses were found, and the number of arteries and veins decreased. The astrocyte network formation was slightly delayed under hyperoxic conditions, and the network became denser in retinas of mice with an episode of hyperoxia. Expression of VEGF levels in the avascular retina of mice that were exposed to hyperoxia was higher than that of control mice. These results suggest that short-term interruption of the onset of vascular development resulting from the reduction in VEGF signals induces abnormal vascular patterns in the mouse retina. The abnormalities in retinal astrocyte behavior might contribute to the formation of an abnormal retinal vascular growth.","PeriodicalId":9120,"journal":{"name":"Birth defects research. Part B, Developmental and reproductive toxicology","volume":"107 6","pages":"216-224"},"PeriodicalIF":0.0,"publicationDate":"2016-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/bdrb.21187","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82105466","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 5

TGF-β1 monoclonal antibody: Assessment of embryo-fetal toxicity in rats and rabbits. TGF-β1单克隆抗体:大鼠和家兔胚胎-胎儿毒性评估。

Birth defects research. Part B, Developmental and reproductive toxicology Pub Date : 2016-08-01 Epub Date: 2016-08-12 DOI: 10.1002/bdrb.21182

Kim G Hilbish, Jennifer A Martin, Anja J Stauber, Tammye L Edwards, William J Breslin

{"title":"TGF-β1 monoclonal antibody: Assessment of embryo-fetal toxicity in rats and rabbits.","authors":"Kim G Hilbish, Jennifer A Martin, Anja J Stauber, Tammye L Edwards, William J Breslin","doi":"10.1002/bdrb.21182","DOIUrl":"https://doi.org/10.1002/bdrb.21182","url":null,"abstract":"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. Maternal reproductive endpoints and fetal viability, weight, and morphology were evaluated. There was no indication of maternal or embryo-fetal toxicity in the rat. Effects in the rabbit were limited to the fetus where the 30 mg/kg TGF-β1 mab dose produced a slight decrease in fetal weight and an increase in the incidence of retrocaval ureter and an absent and/or malpositioned kidney/ureter in two fetuses. In conclusion, TGF-β1 mab produced no adverse maternal or embryo-fetal findings in rats when administered ≤50 mg/kg on GDs 6, 10, and 14. TGF-β1 mab did not demonstrate maternal toxicity or embryo-fetal lethality at doses as high as 30 mg/kg when administered on GDs 7, 12, 14, 16, and 18 in rabbits. Fetal growth and morphology were affected only at 30 mg/kg; thus, the no observed adverse effect level was 3 mg/kg in rabbits. The margin of safety for both rats and rabbits was ≥37-fold the clinical exposure level.","PeriodicalId":9120,"journal":{"name":"Birth defects research. Part B, Developmental and reproductive toxicology","volume":"107 4-5","pages":"174-184"},"PeriodicalIF":0.0,"publicationDate":"2016-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/bdrb.21182","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34751519","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 3

Goldilocks' Determination of What New In Vivo Data are "Just Right" for Different Common Drug Development Scenarios, Part 1. Goldilocks确定哪些新的体内数据对不同的常见药物开发方案“刚刚好”，第1部分。

Birth defects research. Part B, Developmental and reproductive toxicology Pub Date : 2016-08-01 Epub Date: 2016-09-06 DOI: 10.1002/bdrb.21184

Christopher J Bowman, Robert E Chapin

{"title":"Goldilocks' Determination of What New In Vivo Data are \"Just Right\" for Different Common Drug Development Scenarios, Part 1.","authors":"Christopher J Bowman, Robert E Chapin","doi":"10.1002/bdrb.21184","DOIUrl":"https://doi.org/10.1002/bdrb.21184","url":null,"abstract":"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. For example, there is little impact or value of a study in pregnant monkeys to inform the risk assessment for a highly specific monoclonal antibody indicated for a life-threatening indication against a target known to be critical for pregnancy maintenance and fetal survival. In contrast, a small molecule to a novel biological target for a chronic lifestyle indication would warrant more safety data than simply in vitro studies and a literature review. Rather than accounting for innumerable theoretical possibilities surrounding each potential submission's profile, we consolidated most of the typical situations into eight possible scenarios across these three elements, and present a discussion of these scenarios here. We hope that this framework will facilitate a rational approach to determining what new information is required to inform developmental toxicity risk of pharmaceuticals in context of the specific needs of each program while reducing animal use where possible.","PeriodicalId":9120,"journal":{"name":"Birth defects research. Part B, Developmental and reproductive toxicology","volume":"107 4-5","pages":"185-194"},"PeriodicalIF":0.0,"publicationDate":"2016-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/bdrb.21184","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34368790","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 4

Effect of fructose on the phosphorylation of AMP-activated protein kinase and acetyl-CoA carboxylase in HepG2 cells stimulated with placental lactogen. 果糖对胎盘乳原刺激HepG2细胞amp活化蛋白激酶和乙酰辅酶a羧化酶磷酸化的影响。

Birth defects research. Part B, Developmental and reproductive toxicology Pub Date : 2016-08-01 DOI: 10.1002/bdrb.21186

Y. Mukai, Fumika Hoshi, Shin Sato

{"title":"Effect of fructose on the phosphorylation of AMP-activated protein kinase and acetyl-CoA carboxylase in HepG2 cells stimulated with placental lactogen.","authors":"Y. Mukai, Fumika Hoshi, Shin Sato","doi":"10.1002/bdrb.21186","DOIUrl":"https://doi.org/10.1002/bdrb.21186","url":null,"abstract":"BACKGROUND\u0000High 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.\u0000\u0000\u0000METHODS\u0000Human hepatoma cells (HepG2) were treated with D(-)-fructose in the presence or absence of PL. Intracellular lipid contents were measured. The total and phosphorylated protein content of AMPK and acetyl-CoA carboxylase (ACC) was quantified by Western blotting.\u0000\u0000\u0000RESULTS\u0000The intracellular triacylglycerol level in fructose-treated HepG2 cells decreased significantly compared with that in untreated cells in the presence, but not absence, of PL. AMPK and ACC phosphorylation increased significantly and concentration-dependently in fructose-treated HepG2 cells in the presence of PL.\u0000\u0000\u0000CONCLUSION\u0000Our results suggest that fructose treatment reduces triacylglycerol levels via AMPK/ACC signaling in PL-stimulated hepatocytes. These findings suggest that high fructose intake during pregnancy might impair lipid metabolism in the maternal liver.","PeriodicalId":9120,"journal":{"name":"Birth defects research. Part B, Developmental and reproductive toxicology","volume":"107 4-5 1","pages":"206-210"},"PeriodicalIF":0.0,"publicationDate":"2016-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81170258","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 3