Development of a High-Throughput Platform for Screening Ovotoxic Chemicals (K01ES030014)

开发用于筛选卵毒性化学品的高通量平台（K01ES030014）

基本信息

批准号：
10269942
负责人：
Shuo Xiao
金额：
$ 16.24万
依托单位：
RUTGERS, THE STATE UNIV OF N.J.
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-25 至 2023-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10269942
关键词：
3-Dimensional Alginates Animals Apoptosis Architecture Cell Death Cells Chemical Exposure Chemicals Competence Consumption Cryopreservation Dependence Development Dose Encapsulated Ensure Environmental Impact Environmental Pollution Evaluation Female Fertilization Germ Cells Goals Gold Gonadal structure Growth Health Hormone imbalance Hormone secretion Hormones Human Hydrogels Image In Vitro Individual Industrialization Infertility Laboratory Animals Measures Meiosis Methods Mitochondria Molecular Monitor Mus Oocytes Organelles Ovarian Ovarian Follicle Ovary Ovulation Poison Pregnancy Preventive Rapid screening Reaction Time Risk Somatotropin Stains System Technology Temperature Testing Time base cell injury confocal imaging cost cryogenics environmental chemical experimental study female reproductive system high throughput screening imaging system in vitro Model in vivo Model movie oocyte maturation ovarian failure ovotoxicity reproductive function reproductive organ reproductive outcome screening serial imaging steroid hormone

项目摘要

PROJECT SUMMARY Increasing evidence shows that a broad spectrum of both industrial and environmental chemicals can cause female ovarian toxicity (ovotoxicity) and increase the risk of hormonal imbalance, ovarian failure, and infertility in both humans and other mammalian species. The ovary is the primary female reproductive organ and functions to synthesize and secret steroid hormones and to support the oocyte maturation for ovulation, fertilization, and pregnancy. Ovotoxicity can be measured in two ways, from the health of the developing ovarian follicle and gamete and from the ability of the gonads to produce hormones. Unfortunately, the lack of optimal in vitro models makes the current gold standard for testing the ovotoxicity of chemicals rely on the use of laboratory animals. However, in vivo models are time-consuming, costly, and harmful to animals. In our previous studies, we have used an alginate hydrogel-based encapsulation method to grow both mouse and human preantral follicles outside of the context of the ovary, which is termed encapsulated in vitro follicle growth (eIVFG). The eIVFG maintains the 3D architecture of the follicles and supports follicle growth, hormone secretion as well as oocyte maturation and ovulation, suggesting a promising model for in vitro ovotoxicity testing. However, this method is relatively slow, and multiple rounds of follicle isolation, culture, and chemical exposure are necessary to complete dose-response and time-course experiments, making the current eIVFG scenario not optimal, particularly when a rapid screening is required in the case of unpredictable and emerging environmental threats. In this proposed project, we hypothesize that we can use cryopreservation technology and a confocal high-content imaging system to develop a high-throughput platform for screening ovotoxic chemicals. In Aim 1, we will bank the isolated ovarian follicles through vitrification for establishing a long-term and ready-to-use follicle storage platform. In Aim 2, we will use the ImageXpress confocal high-content imaging system to develop a high-throughput platform for follicle monitoring, assessing, and analysis. We expect that these proposed studies will allow us to obtain rapid and reliable evidences to understand the impacts of environmental contaminants on the female reproductive system, to provide guidance to conduct preventive and protective activities, as well as to minimize the dependence and use of animals.

项目概要越来越多的证据表明，多种工业和环境化学品都可能导致女性卵巢毒性（卵毒性）并增加荷尔蒙失衡、卵巢功能衰竭和不孕的风险在人类和其他哺乳动物中，卵巢是主要的女性生殖器官和功能。合成和分泌类固醇激素并支持卵母细胞成熟以进行排卵、受精和卵毒性可以通过两种方式来测量：发育中的卵泡的健康状况和卵泡的健康状况。不幸的是，缺乏最佳的体外模型。使得当前测试化学品卵毒性的金标准依赖于实验动物的使用。然而，在我们之前的研究中，体内模型耗时、昂贵且对动物有害。使用基于藻酸盐水凝胶的封装方法来培养小鼠和人类的腔前卵泡在卵巢之外，这被称为封装体外卵泡生长（eIVFG）。维持卵泡的 3D 结构并支持卵泡生长、激素分泌以及卵母细胞成熟和排卵，表明体外卵毒性测试的一个有前途的模型。相对缓慢，需要多轮卵泡分离、培养和化学暴露才能完成剂量反应和时程实验，使得当前的 eIVFG 方案不是最佳的，特别是当在出现不可预测的和新出现的环境威胁的情况下，需要进行快速筛查。项目中，我们认为可以使用冷冻保存技术和共焦高内涵成像系统开发用于筛选卵毒性化学品的高通量平台在目标 1 中，我们将存储通过玻璃化冷冻分离卵泡，建立长期、即用的卵泡储存平台。在目标 2 中，我们将使用 ImageXpress 共焦高内涵成像系统来开发高通量我们期望这些拟议的研究将使我们能够实现卵泡监测、评估和分析的平台。获得快速可靠的证据以了解环境污染物对女性的影响生殖系统，为开展预防和保护活动提供指导，并尽量减少对动物的依赖和利用。

项目成果

期刊论文数量（5）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

An ex vivo ovulation system enables the discovery of novel ovulatory pathways and nonhormonal contraceptive candidates†.

体外排卵系统能够发现新的排卵途径和非激素避孕候选药物。

DOI：
发表时间：
2023-04-11
期刊：
影响因子：
3.6
作者：
Zhang, Jiyang;Goods, Brittany A;Pattarawat, Pawat;Wang, Yingzheng;Haining, Tessa;Zhang, Qiang;Shalek, Alex K;Duncan, Francesca E;Woodruff, Teresa K;Xiao, Shuo
通讯作者：
Xiao, Shuo

Associations between exposure to cadmium, lead, mercury and mixtures and women's infertility and long-term amenorrhea.

接触镉、铅、汞及其混合物与妇女不孕和长期闭经之间的关联。

DOI：
发表时间：
2023-08-25
期刊：
影响因子：
0
作者：
McClam, Maria;Liu, Jihong;Fan, Yihan;Zhan, Tingjie;Zhang, Qiang;Porter, Dwayne E;Scott, Geoffrey I;Xiao, Shuo
通讯作者：
Xiao, Shuo

Bioengineering models of female reproduction.

女性生殖的生物工程模型。

DOI：
发表时间：
2020-09
期刊：
影响因子：
0
作者：
Zubizarreta, Maria E;Xiao, Shuo
通讯作者：
Xiao, Shuo

Health impacts of environmental contamination of micro- and nanoplastics: a review.

微塑料和纳米塑料环境污染对健康的影响：综述。

DOI：
发表时间：
2020-07-14
期刊：
影响因子：
0
作者：
Jiang, Baorong;Kauffman, Alexandra E;Li, Lei;McFee, Wayne;Cai, Bo;Weinstein, John;Lead, Jamie R;Chatterjee, Saurabh;Scott, Geoffrey I;Xiao, Shuo
通讯作者：
Xiao, Shuo

Preserving Oocytes in Oncofertility†.

在肿瘤生育中保存卵母细胞。