The Role of Leptin in Luteal Angiogenesis (pilot)

瘦素在黄体血管生成中的作用（试点）

• 批准号: 8019541
• 负责人: MICHELLE R GARCIA
• 金额: $ 1.84万
• 依托单位: TEXAS A&M UNIVERSITY-KINGSVILLE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8019541
• 关键词: ANGPT1 gene; Accounting; Adipocytes; Angiogenic Factor; Angiopoietin-1; Anterior Pituitary Gland; Basement membrane; Biochemical; Biomedical Research; Blood Vessels; Blood capillaries; Brain; DNA; Data; Defect; Development; Discontinuous Capillary; Dissociation; Elements; Environment; Estrous Cycle; Experimental Models; Exposure to; FGF2 gene; Family suidae; Female; Fibroblast Growth Factor; Fibroblast Growth Factor 2; Gene Expression; Gene Proteins; Genetic Transcription; Goat; Graafian Follicles; Habitual Abortion; Histologic; Hormones; Human; Infertility; Leptin; Livestock; Luteal Phase; Luteinizing Hormone; Mediating; Messenger RNA; Metabolic; Modeling; Orthopedics; Ovarian; Ovarian Tissue; Ovary; Ovulation; Photoperiod; Physiological; Physiology; Play; Pregnancy Maintenance; Primates; Process; Production; Progesterone; Prolactin; Property; Proteins; Psychology; Regulation; Reporting; Research; Rodent; Rodent Model; Role; Satiation; Signal Transduction; Site; Source; South Texas; Staging; Structure; Texas; Theca folliculi structure; Tissues; Transcription Factor AP-1; Transcriptional Activation; Universities; Up-Regulation; Vascular Endothelial Growth Factors; Vascularization; Woman; angiogenesis; capillary; corpus luteum; cost; in vivo; leptin receptor; protein expression; reproductive; research study; steroid hormone

The corpus luteum (CL) is an ovarian structure that produces the steroid hormone progesterone, which is imperative to the maintenance of pregnancy in mammalian species. Corpora luteal defects contribute to infertility issues in women and are believed to account for approximately 65% of recurrent miscarriages. These luteal defects include abnormal luteal development and decreased progesterone production, which are attributed, in part, to abnormal angiogenesis, i.e., vascular formation. In the ovary, angiogenesis is a cyclical, recurring process that takes place following the ovulation of a mature follicle initiated by a surge of secreted luteinizing hormone (LH) from the anterior pituitary of the brain. Upon ovulation, the capillaries in the theca interna are able to penetrate the avascular, granulosal layer, as a result of the dissociation of the basement membrane, and form a network of sinusoidal capillaries. There are many factors known to regulate luteal angiogenesis, including vascular endothelial growth factor (VEGF), fibroblast growth factor 2 (FGF-2), angiopoietin 1 (Ang-1), and leptin. All of these factors are reported to be produced in the ovary; moreover, VEGF, Ang-1, and FGF-2 are reported to be produced in luteal tissue corresponding to periods of high angiogenic activity. Upregulation of luteal VEGF, FGF-2, and Ang-1 gene expression occurs following exposure to the luteotropic hormone LH, which also stimulates ovarian production of leptin, a potent satiety hormone. Leptin is an important metabolic hormone produced by adipocytes that is known to have both reproductive and potent angiogenic functional properties. Furthermore, leptin is known to influence the function of VEGF, FGF-2, and Ang-1 in non-ovarian tissues. Moreover, the fully functional form of the leptin receptor (OB-Rb) has been identified in luteal tissue and stimulates a signal transduction cascade that activates the AP-1 DNA element, a site known to initiate gene transcription of VEGF, FGF-2, and Ang-1. Therefore, LH may initiate the vascularization process by influencing the gene expression of VEGF, FGF- 2, Ang-1, and leptin. Leptin may then further mediate the effects of LH, influencing the angiogenic process through its regulation or interaction with the other luteal angiogenic factors. Hence, the role of leptin in the angiogenic processes of luteal tissue is not well-defined, but, leptin's ability to influence VEGF, FGF-2, and Ang-1 in various non-ovarian tissues, the presence of OB-Rb in luteal tissue, and OB-Rb's ability to activate a signal transduction cascade known to regulate transcriptional activation of VEGF, FGF-2, and Ang-1 suggests that leptin may play a role in luteal angiogenesis. Therefore, the specific aims of the study proposed herein are to 1) histologically identify spatial and temporal localization of VEGF, Ang-1, FGF-2, and OB-Rb in luteal tissue during the different stages of the luteal phase, 2) quantitate the temporal relationship among VEGF, Ang-1, FGF-2, and OB-Rb mRNA and protein in the CL during different stages of the luteal phase, 3) determine leptin's ability to influence VEGF, Ang-1, and FGF-2 gene and protein expression in luteal tissue during the early-, mid-, and late luteal phase of the estrous cycle, and 4) determine the role of leptin on luteal angiogenesis in vivo.

黄体（CL）是一个卵巢结构，产生类固醇激素黄体酮，这是必要的