权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Paternal Environmental Exposures and Reproductive Outcomes: A Comparison of in Vi

父亲的环境暴露和生殖结果：Vi 中的比较

基本信息

批准号：
8195237
负责人：
Deborah Ann Hansen
金额：
--
依托单位：
ST. LOUIS VA MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-05-01 至 2013-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8195237
关键词：
Address Affect Aftercare Aryl Hydrocarbon Receptor Biochemical Birth Birth Weight CYP1A1 gene Cell Line Cells Child Conceptions Congenital Abnormality Decidual Cell Reactions Dental crowns Development Dioxins Embryo Embryonic Development Endocrine Environment Environmental Exposure Event Exposure to Female Fertility Fertilization Fertilization in Vitro Fetal Weight Future Generations Genetic Germ Cells Glucose Transporter Growth Gulf War Herbicides In Situ Nick-End Labeling In Vitro Laws Length Litter Size Low Birth Weight Infant Malignant Childhood Neoplasm Measures Mediating Messenger RNA Microscopic Military Personnel Mus Neurosecretory Systems Nutrient Outcome Partner in relationship Paternal Exposure Pesticides Pregnancy Prevention Process Radiation Receptor Activation Reporting Research Research Design Research Methodology Reverse Transcriptase Polymerase Chain Reaction Role Seminal fluid Services Spermatogenesis Spinal Dysraphism Staging Stromal Cells Structure Toxic effect Toxin Vagina Veterans Vietnam Weight Gain Writing absorption abstracting agent orange blastocyst blastomere structure design embryo cell environmental agent expectation implantation in vivo male reproductive sperm cell

项目摘要

Abstract Title: Paternal Environmental Exposures and Reproductive Outcomes: A Comparison of in vitro and in vivo Fertilization Statement of the Problem: Nine hundred children with Spina Bifida of Agent Orange exposed Vietnam veterans receive VA presumptive service connected benefits. Developmental endpoints such as structural birth defects, failed pregnancy, low birth weight, increased childhood cancers; and developmental, endocrine, and biochemical abnormalities have been reported in F1 and F2 generations following paternal exposures to pesticides, herbicides, and radiation. Multiple mechanisms of action are implicated in male mediated adverse reproductive events to include: a) toxins in semen that can result in vaginal absorption and in exposure of the embryo post conception, and b) deleterious effects that can disrupt fertility through interaction with the neuroendocrine axis. To our knowledge no studies examine the role of paternal preconception exposure to environmental agents on the reproductive outcomes by separating sperm related factors from seminal fluid factors through a comparison of in vitro and in vivo fertilization. Research Objectives: The primary objective is to characterize the effects of male preconception dioxin exposure on selected parameters of natural mating as well as in vitro fertilization. Murine in vitro fertilization circumvents female seminal fluid contact thereby separating the effect of vaginal absorption of toxins and the exposure of the embryo to these toxins post conception from any genetic effects on the male germ cells. The secondary objective is to determine if aryl hydrocarbon receptor (AHR) activation affects glucose transporter (GLUT) 1 localization in either the blastocyst stage embryo or stromal cell of the uterine environment, thus having a detrimental effect on embryo development and/or implantation respectively. AHR activation has been shown to alter GLUT 1 localization in an embryonic cell line thereby resulting in nutrient deficient cells and providing one explanation of Dioxin's embryo toxic effects. Research Methods: An experimental 2 x 2 block design at T+14 and T+35 days post treatment will be used to characterize the reproductive outcomes that result from in vivo natural mating vs. in vitro fertilization of non exposed females with Dioxin exposed and non exposed males. In vivo reproductive measures include 3.5 day post coitum (dpc): a) blastocyst numbers; b) blastocyst TUNEL, CYP1A1, and GLUT levels and localization; c) RT-PCR of in vivo blastocyst and stromal cell CYP1A1 mRNA, and d) stromal cell decidualization. In vivo and in vitro parameters include: a) 14.5 dpc placental and fetal weights, and crown to rump lengths; b) full term litter size, birth weights, and 5 week growth rates; and c) gross and microscopic structure.

摘要