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

• 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
• 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

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.

抽象的 标题：父亲的环境暴露和生殖结果：体外比较 和体内受精 问题陈述：橙剂暴露于九百名患有脊柱裂的儿童 越南退伍军人领取退伍军人管理局推定服役相关福利。发育终点 例如结构性出生缺陷、妊娠失败、低出生体重、儿童癌症增加； F1 和 F2 中均报告有发育、内分泌和生化异常 父亲接触杀虫剂、除草剂和辐射后的后代。多种的 与男性介导的不良生殖事件有关的作用机制包括： a) 精液中的毒素会导致阴道吸收和胚胎移植后暴露 受孕，以及 b) 通过与体内相互作用而破坏生育能力的有害影响 神经内分泌轴。据我们所知，没有研究检验父亲先入为主的作用 通过分离与精子相关的环境因素对生殖结果的影响 通过比较体外和体内受精，从精液因素中找出因素。 研究目标：主要目标是描述男性先入为主的影响 二恶英暴露对自然交配和体外受精的选定参数的影响。鼠类 体外受精规避了女性精液接触，从而分离了 阴道吸收毒素以及胚胎在受孕后暴露于这些毒素 免受对男性生殖细胞的任何遗传影响。第二个目标是确定芳基是否 碳氢化合物受体 (AHR) 激活影响葡萄糖转运蛋白 (GLUT) 1 在 囊胚期胚胎或子宫环境的基质细胞，因此具有 分别对胚胎发育和/或植入产生有害影响。 AHR 激活 已被证明可以改变胚胎细胞系中的 GLUT 1 定位，从而导致 营养缺乏的细胞并为二恶英的胚胎毒性作用提供了一种解释。 研究方法：治疗后 T+14 和 T+35 天的实验性 2 x 2 区组设计 将用于表征体内自然交配产生的生殖结果 与未暴露的雌性与二恶英暴露和未暴露的雄性的体外受精进行比较。在 体内生殖测量包括性交后 3.5 天 (dpc)： a) 囊胚数量； b) 囊胚 TUNEL、CYP1A1 和 GLUT 水平和定位； c) 体内囊胚的RT-PCR 和基质细胞 CYP1A1 mRNA，以及 d) 基质细胞蜕膜化。体内和体外 参数包括： a) 14.5 dpc 胎盘和胎儿重量，以及头臀长； b) 满 足月产仔数、出生体重和 5 周生长率； c) 总体和微观结构。