Characterizing the effect of bisphenol-A on the metabolism of maternally derived

表征双酚 A 对母源代谢的影响

• 批准号: 8688601
• 负责人: RACHEL M BOWDEN
• 金额: $ 42.57万
• 依托单位: ILLINOIS STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-05-15 至 2018-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8688601
• 关键词: Address; Binding; Birds; Blood Circulation; Buffers; Chemicals; Corticosterone; Data; Development; Diagnostic; Dose; Ear; Embryo; Endocrine; Endocrine Disruptors; Endocrine disruption; Environment; Enzymes; Estradiol; Estrogen Metabolism; Estrogens; Estrone-Sulfate; Exposure to; Fetus; Goals; Investigation; Journals; Ligands; Light; Mediating; Metabolic; Metabolism; Modeling; Organism; Oviparity; Paper; Pathway interactions; Peer Review; Phenotype; Placenta; Pregnancy; Production; Progesterone; Reptiles; Research; Route; Schools; Signal Transduction; Slide; Steroid Receptors; Steroids; Students; System; Testing; Testosterone; Turtles; Vertebrates; Work; bisphenol A; chemical group; design; environmental chemical; inhibitor/antagonist; man; meetings; offspring; programs; public health relevance; sex; sex determination; steroid metabolism; sulfotransferase; tool; undergraduate student

DESCRIPTION (provided by applicant): All vertebrate embryos develop in the presence of maternally derived steroids and accumulating evidence suggests that these steroids are subject to prolific embryonic metabolism. This metabolism is frequently thought of as a "buffer" that regulates embryonic exposure to maternal steroids. The recent demonstration that maternally derived estradiol is converted to estrone sulfate early in development and that the endocrine disrupting chemical bisphenol-A inhibits this conversion has prompted further investigation to understand how bisphenol-A disrupts steroid metabolism and the long-term consequences of this disruption. The proposed research utilizes a wild turtle model that provides an excellent system for evaluating the interaction between maternal steroids, endocrine disruption, and metabolism because: (1) steroids and steroidogenic enzymes are conserved across vertebrates, (2) turtle embryos are very amenable to experimental manipulation, and (3) sex determination in turtles is sensitive to steroids and endocrine disrupting chemicals which provides a diagnostic tool for assessing endocrine disruption. The first aim of the proposal will determine if bisphenol-A is a ubiquitous inhibitor of steroid sulfonation. This aim will characterie the metabolic fate of progesterone, testosterone, and corticosterone during early development and test the hypothesis that BPA is broadly capable of inhibiting embryonic metabolism of steroids. To accomplish this aim, exogenous steroid and bisphenol-A manipulations will be used to determine metabolite formation during early development. The second aim of the proposal will determine the inhibiting effects of bisphenol-A on the in ovo metabolism of maternally derived estradiol. This aim will test the hypothesis that inhibition of normal embryonic steroid metabolism has phenotypic consequences for the resulting hatchling. To accomplish this aim, exogenous manipulations will also be employed to assess the effects of these manipulations on offspring sex. The results from this work will provide important new information on endocrine disruption that may extend beyond the effects of bisphenol-A, and shed light on an underlying mechanism for non-receptor mediated pathways for endocrine disruptor activity.

描述（由申请人提供）：所有脊椎动物胚胎在存在于母体衍生的类固醇和积累证据的情况下发展出来，表明这些类固醇受到多产的胚胎代谢。这种代谢经常被认为是一种“缓冲液”，可调节胚胎暴露于母体类固醇。最近在发育早期将母体衍生的雌二醇转化为硫酸雌激素的证明，并且内分泌干扰化学双酚A抑制这种转化促进了进一步的研究，以了解Bisphenol-A如何破坏类固醇的代谢和这种破坏的长期后果。 The proposed research utilizes a wild turtle model that provides an excellent system for evaluating the interaction between maternal steroids, endocrine disruption, and metabolism because: (1) steroids and steroidogenic enzymes are conserved across vertebrates, (2) turtle embryos are very amenable to experimental manipulation, and (3) sex determination in turtles is sensitive to steroids and endocrine disrupting chemicals which provides用于评估内分泌干扰的诊断工具。该提案的第一个目的将确定双酚A是否是普遍存在的类固醇硫化抑制剂。该目标将在早期发育过程中表征孕酮，睾丸激素和皮质酮的代谢命运，并检验BPA广泛能够抑制类固醇的胚胎代谢的假设。为了实现这一目标，外源性类固醇和双酚A操作将用于确定早期发育过程中代谢产物的形成。该提案的第二个目的将确定双足A对母体衍生的雌二醇的OVO代谢的抑制作用。该目标将检验以下假设：抑制正常的胚胎类固醇代谢对产生的孵化具有表型后果。为了实现这一目标，还将采用外源操纵来评估这些操纵对后代性别的影响。这项工作的结果将提供有关内分泌干扰的重要新信息，该信息可能超出双酚A的影响，并阐明了无受体介导的内分泌干扰物活性途径的基本机制。

项目成果

Characterizing the distribution of steroid sulfatase during embryonic development: when and where might metabolites of maternal steroids be reactivated?

描述胚胎发育过程中类固醇​​硫酸酯酶的分布：母体类固醇的代谢物何时何地可能被重新激活？

• DOI: 10.1242/jeb.167031
• 发表时间: 2017
• 期刊: The Journal of experimental biology
• 作者: Paitz,RyanT;Duffield,KristinR;Bowden,RachelM
• 通讯作者: Bowden,RachelM

Red-eared slider hatchlings (Trachemys scripta) show a seasonal shift in behavioral types.

红耳龟幼龟（Trachemys scripta）的行为类型呈现季节性变化。

• DOI: 10.1002/jez.2315
• 发表时间: 2019
• 期刊: Journal of experimental zoology. Part A, Ecological and integrative physiology
• 作者: Nichols,Haley;Carter,AmandaW;Paitz,RyanT;Bowden,RachelM
• 通讯作者: Bowden,RachelM

Temperature fluctuations and maternal estrogens as critical factors for understanding temperature-dependent sex determination in nature.

• DOI: 10.1002/jez.2183
• 发表时间: 2018-04
• 期刊: Journal of experimental zoology. Part A, Ecological and integrative physiology
• 作者: Bowden RM;Paitz RT
• 通讯作者: Paitz RT

Short heatwaves during fluctuating incubation regimes produce females under temperature-dependent sex determination with implications for sex ratios in nature.

• DOI: 10.1038/s41598-017-17708-0
• 发表时间: 2018-01-08
• 期刊: Scientific reports
• 影响因子: 4.6
• 作者: Carter AW;Sadd BM;Tuberville TD;Paitz RT;Bowden RM
• 通讯作者: Bowden RM

Learning and behavior in hatchling Trachemys scripta exposed to bisphenol-a during embryonic development.

在胚胎发育过程中暴露于双酚-a 的Trachemys scripta 幼体的学习和行为。

• DOI: 10.1016/j.physbeh.2019.112614
• 发表时间: 2019
• 期刊: Physiology & behavior
• 影响因子: 2.9
• 作者: Dillard,Justin;Carter,AmandaWilson;Ower,GeoffD;Paitz,RyanT;Bowden,RachelM
• 通讯作者: Bowden,RachelM