关键词: 4-vinylcyclohexene diepoxide controlled ovarian hyperstimulation dehydroepiandrosterone phosphatase and tensin homolog of chromosome 10/phosphoinositide 3-kinase/protein kinase B (PTEN/PI3K/AKT) signaling pathway premature ovarian insufficiency

Mesh : Animals Female Primary Ovarian Insufficiency / chemically induced metabolism PTEN Phosphohydrolase / metabolism Vinyl Compounds Cyclohexenes / pharmacology Signal Transduction / drug effects Proto-Oncogene Proteins c-akt / metabolism Dehydroepiandrosterone / pharmacology administration & dosage Phosphatidylinositol 3-Kinases / metabolism Rats Rats, Sprague-Dawley Ovary / drug effects metabolism Ovarian Reserve / drug effects Ovarian Follicle / drug effects metabolism

来  源:   DOI:10.1538/expanim.23-0179   PDF(Pubmed)

Abstract:
Dehydroepiandrosterone (DHEA) is frequently integrated as an adjuvant in over a quarter of controlled ovarian hyperstimulation (COH) protocols, despite the ongoing debate regarding its impact. This study aimed to evaluate the efficacy and mechanism of action of DHEA on ovarian follicular development and ovarian response in rats with varying ovarian reserves. The study involved 75 rats categorized into 15 distinct groups. The ovarian tissues of rats in both the normal ovarian reserve group and the premature ovarian insufficiency (POI) group, induced by 4-vinylcyclohexene diepoxide (VCD) injection, were subjected to histomorphological and biochemical analyses following the administration of DHEA, either alone or in combination with COH. Follicle counting was performed on histological sections obtained from various tissues. Serum concentrations of anti-Müllerian hormone (AMH) and the quantification of specific proteins in ovarian tissue, including phosphatase and tensin homolog of chromosome 10 (PTEN), phosphoinositide 3-kinase (PI3K), phosphorylated protein kinase B (pAKT), cyclooxygenase 2 (COX-2), caspase-3, as well as assessments of total antioxidant status and total oxidant status, were conducted employing the ELISA method. The impact of DHEA exhibited variability based on ovarian reserve. In the POI model, DHEA augmented follicular development and ovarian response to the COH protocol by upregulating the PTEN/PI3K/AKT signaling pathway, mitigating apoptosis, inflammation, and oxidative stress, contrary to its effects in the normal ovarian reserve group. In conclusion, it has been determined that DHEA may exert beneficial effects on ovarian stimulation response by enhancing the initiation of primordial follicles and supporting antral follicle populations.
摘要:
脱氢表雄酮(DHEA)经常被整合为超过四分之一的控制性卵巢过度刺激(COH)方案的佐剂,尽管有关其影响的辩论仍在进行中。本研究旨在评估DHEA对不同卵巢储备的大鼠卵巢卵泡发育和卵巢反应的功效和作用机制。该研究涉及75只大鼠,分为15个不同的组。卵巢储备正常组和卵巢早衰(POI)组大鼠卵巢组织,4-乙烯基环己烯二环氧化物(VCD)注射诱导,在施用DHEA后进行组织形态学和生化分析,单独或与COH组合。对从各种组织获得的组织切片进行卵泡计数。AMH的血清浓度和卵巢组织中特定蛋白质的定量,包括PTEN,PI3K,AKT,COX-2,caspase-3,以及总抗氧化剂状态和总氧化剂状态的评估,采用酶联免疫吸附测定(ELISA)方法进行。DHEA的影响表现出基于卵巢储备的变异性。在POI模型中,DHEA通过上调PTEN/PI3K/pAKT信号通路增强卵泡发育和卵巢对COH方案的反应,减轻细胞凋亡,炎症,和氧化应激,与其在正常卵巢储备组中的作用相反。总之,已经确定,DHEA可能通过增强原始卵泡的启动和支持窦卵泡群体而对卵巢刺激反应产生有益作用.
公众号