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H2S and Endometrial Angiogenesis

H2S 与子宫内膜血管生成

基本信息

批准号：
10039472
负责人：
DONGBAO CHEN
金额：
$ 7.85万
依托单位：
UNIVERSITY OF CALIFORNIA-IRVINE
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：
2020-08-01 至 2022-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10039472
关键词：
Angiogenesis Promoter Angiogenic Factor Applications Grants Area Arteries Biology Biopsy Birth Cell Culture Techniques Cell model Cells Cesarean section Coculture Techniques Cystathionine Cysteine Data Decidual Cell Reactions Discipline of obstetrics Disease Embryo Endometrial Endometrial Stromal Cell Endometrium Endothelial Cells Enzymes Estradiol Estrogen Receptor alpha Estrogen Receptor beta Estrogen Receptors Estrogens Female Fertility Future Genetic Transcription Goals Gonadal Steroid Hormones Grant Gynecologic Human Hydrogen Sulfide Hysterectomy Impairment In Vitro Infertility Investigation Knock-out Link Lyase Malignant Neoplasms Mammalian Oviducts Maternal-fetal medicine Mediating Menstrual cycle Modeling Mus Natural regeneration Organ Outcome Periodicity Phase Physiological Placentation Play Postmenopause Pre-Eclampsia Pregnancy Pregnancy Maintenance Process Production Progesterone Regulation Replacement Therapy Reporting Reproduction Research Role Sampling Signaling Molecule Smooth Muscle Steroidal Estrogen System Testing Time Tissues Up-Regulation Uterus Vascular Endothelial Growth Factors Vasodilation Vasodilator Agents Woman angiogenesis endometriosis in vivo indexing migration new therapeutic target novel paracrine pregnant proliferative phase Menstrual cycle promoter protein expression trophoblast

项目摘要

Project Summary New vessel formation from existing vessels termed angiogenesis is a key mechanism for endometrial turnover and regeneration during the menstrual cycle and normal pregnancy during which estrogens play a critical role. Angiogenesis in endometrium, like it occurs in any other organs, is initiated by enhanced local production of angiogenic factors. Hydrogen sulfide (H2S) is a gaseous signaling molecule that participates into the regulation of numerous physiological and pathophysiological processes. Endogenous H2S is mainly produced from L-cysteine by cystathionine-β-synthase (CBS) and cystathionine-γ-lyase (CSE). H2S is a potent proangiogenic vasodilator because H2S donors promote endothelial cell (EC) angiogenesis in vitro and in vivo. CBS and CSE have been found in many organs but their expression is tissue/cell-specific; both are needed to generate H2S in some tissues while one enzyme is sufficient in others. Recent studies have implicated a role of H2S in regulating endometrial function during the menstrual cycle and pregnancy; however, hitherto it has reported whether endometrial H2S generating system is regulated during the menstrual cycle and pregnancy and whether H2S plays a role in endometrial angiogenesis. The overall hypothesis of this RO3 is that elevated estrogens stimulate estrogen receptor (ERα/β) dependent upregulation of stromal CBS-H2S production, which in turn stimulates EMEC angiogenesis during the proliferative phase and pregnancy in women. This hypothesis will be tested by using endometrial biopsies from Cesarean hysterectomies and primary endometrial stromal cells (ESC) and endometrial microvascular endothelial cells (EMEC) cell models derived from these tissues. Aim 1 will determine if endometrial H2S production correlates to endometrial angiogenesis index under the influence of endogenous estrogens in women ex vivo; Aim 2 To determine if estrogens stimulate ESC H2S production is mediated via ER (ERα/ER) dependent CBS transcription and in vitro; and Aim 3 will determine if ESC-derived H2S mediates estrogen stimulation of EMEC angiogenesis. Accomplishing these important specific aims will establish a new paracrine physiological role of ESC-derived H2S in endometrial EMEC angiogenesis.

项目总结