Sexual dimorphism in embryo responses to maternal regulatory factors

胚胎对母体调节因素反应的性别二态性

基本信息

批准号：
8752049
负责人：
Peter J. Hansen
金额：
$ 6.96万
依托单位：
UNIVERSITY OF FLORIDA
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-08-01 至 2016-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8752049
关键词：
Animals Apoptosis Cattle Cell Count Cells Characteristics Colony-Stimulating Factors Competence Data Development Embryo Embryonic Development Endoderm Endometrium Environment Epiblast Family suidae Female Female infertility Fertility Fertilization in Vitro Flushing Gender Gene Expression Gene Expression Profile Goals Growth Factor Health Human In Vitro Inhibition of Apoptosis Inner Cell Mass Insulin-Like Growth Factor I Laboratories Lead Life Mammalian Oviducts Mediating Modeling Modification Molecular Morula Mothers Mus Newborn Animals Obesity Outcome Personal Satisfaction Pregnancy Pregnancy loss Procedures Process Proteins Recovery Regulation Research Risk Sex Characteristics Signal Transduction Sorting - Cell Movement Staging Testing Therapeutic Variant Woman base blastocyst cytokine fetal improved male meetings methylome novel therapeutic intervention postnatal preimplantation programs public health relevance reproductive research study response sexual dimorphism sperm cell tau interferon

项目摘要

DESCRIPTION (provided by applicant): The developmental program of the preimplantation embryo is readily modified by alterations in the microenvironment. The resultant change in trajectory of development can have long-acting effects that extend into post-natal life. Male and female embryos can respond differently to environmental modification during the preimplantation period. Recent data from our laboratory with bovine embryos indicate that sexual dimorphism in response to changes in the microenvironment could be mediated by gender-specific responses to maternal regulatory signals. Treatment of embryos with colony-stimulating factor 2 (CSF2) from Day 5-7 of development caused gender-specific alterations in characteristics of embryos after transfer to females and recovery at Day 15 of gestation. If this phenomenon of sexual dimorphism is a general one, gender-specific analysis will be required to understand basic mechanisms controlling development, environmental effects on embryonic development, and therapeutic approaches to improving fertility in women. The current proposal seeks to determine the extent to which regulation of embryonic development depends on gender. There are two immediate goals: to develop a model for understanding the molecular basis for how CSF2 exerts gender-specific effects on embryonic development and to evaluate whether the phenomenon of sexual dimorphism in regulation of preimplantation development is widespread (i.e., exists for more than one regulatory molecule). To meet these objectives, we will take advantage of a large amount of preliminary data from our laboratory that describes how CSF2 and two other uterine regulatory factors, insulin-like growth factor 1 (IGF1) and dickkopf-related protein 1 (DKK1), modify development of the bovine blastocyst. In particular, we will test whether actions of CSF2, IGF1 and DKK1 on embryos seen previously occur in a gender-specific manner when embryos are produced using X- or Y-sorted spermatozoa. For Aim 1, gender differences in response of bovine morulae and blastocysts to CSF2 will be determined. Four experiments will be conducted to evaluate sexual dimorphism in regulation of the embryo by CSF2 with respect to gene expression in morulae and blastocysts, inhibition of apoptosis, and increase in numbers of cells in the inner cell mass of the blastocyst. Aim 2 will determine whether sexual dimorphism exists for other regulatory factors by testing whether IGF1 and DKK1 exert actions on bovine embryos in a gender-specific manner. Experiments will be performed to determine differences between male and female embryos with respect to IGF1 actions on blastocyst development, gene expression and apoptosis and with respect to DKK1 actions on allocation of cells in the blastocyst to cells of the epiblast, primitive endoderm, and trophectoderm lineages. These experiments are important to develop research models for delineating mechanisms by which sexual dimorphism is established (Aim 1) and to determine the importance of sexual dimorphism as an important determinant of regulation of embryonic development (Aim 2).

描述（由申请人提供）：植入前胚胎的发展程序很容易通过微环境的改变来修改。最终的发展轨迹变化可能会产生长效效应，从而延伸到产后生活。在植入前时期，男性和女性胚胎对环境改变的反应不同。我们实验室使用牛胚胎的最新数据表明，对微环境变化的响应性二态性可以通过对母体调节信号的特定性别反应来介导。从发育的第5-7天开始，用刺激性因子2（CSF2）处理胚胎会导致转移至女性的胚胎特征的特异性改变，并在妊娠第15天恢复。如果这种性二态性的现象是一种普遍的现象，则需要针对特定性别的分析来了解控制发展发展的基本机制，对胚胎发育的环境影响以及改善女性生育能力的治疗方法。当前的提案旨在确定胚胎发展的调节程度取决于性别。有两个直接的目标：开发一个模型来理解CSF2如何对胚胎发育施加性别特异性影响，并评估性二态性在调节前植入前发展中的现象是否广泛（即，存在超过一个）调节分子）。为了实现这些目标，我们将利用实验室的大量初步数据，这些数据描述了CSF2和其他两个子宫调节因素如何（胰岛素样生长因子1（IGF1）和与DickkoPF相关的蛋白质1（DKK1））修改牛胚泡的发育。特别是，当使用X-或Y-Sort的精子产生胚胎时，我们将测试CSF2，IGF1和DKK1对先前以性别特异性的胚胎的作用。对于目标1，将确定牛莫拉和胚泡对CSF2的反应性别差异。将进行四个实验，以评估CSF2在莫拉和胚泡中基因表达的胚胎调节中的性二态性，抑制凋亡以及胚泡内部细胞内细胞中细胞数量的增加。 AIM 2将通过测试IGF1和DKK1是否以性别特定方式对牛胚胎发挥作用来确定其他调节因素是否存在性二态性。将进行实验，以确定雄性和女性胚胎在IGF1对胚泡发育，基因表达和凋亡方面的作用方面的差异，以及DKK1对胚泡分配胚细胞对细胞的分配到细胞，原始内胚层和滋养表二甲体的作用的差异。。这些实验对于建立性二态性的描述机制的研究模型很重要（AIM 1），并确定性二态性作为胚胎发育调节的重要决定因素的重要性（AIM 2）。