Investigating the Dysregulation of the Hippo-Related ceRNA Network and Its Impact on IVF Outcomes in Patients With Diminished Ovarian Reserve (DOR)
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 70
- 试验地点
- 1
- 主要终点
- Expression levels of Nuclear Paraspeckle Assembly Transcript 1 (NEAT1), microRNA-181a-5p (miR-181a-5p), Yes-Associated Protein 1 (YAP1), and Connective Tissue Growth Factor (CTGF).
研究概览
简要总结
Diminished Ovarian Reserve (DOR) is an important cause of female infertility and is associated with poor ovarian response and lower pregnancy rates during In Vitro Fertilization (IVF). The molecular mechanisms underlying impaired follicular development in DOR remain incompletely understood. Increasing evidence suggests that non-coding RNAs and components of the Hippo signaling pathway play important roles in granulosa cell proliferation, apoptosis, and follicular development.
This prospective observational cohort study aims to investigate the expression of the long non-coding RNA (lncRNA) Nuclear Paraspeckle Assembly Transcript 1 (NEAT1), microRNA (miRNA)-181a-5p, Hippo pathway components including Yes-Associated Protein 1 (YAP1) and Connective Tissue Growth Factor (CTGF), and Insulin-Like Growth Factor 1 (IGF1) in follicular fluid-derived cells from women with DOR undergoing IVF compared with women with normal ovarian reserve. The study will also evaluate relationships among these molecular markers and IVF outcomes, including oocyte quality, number of retrieved oocytes, and embryo developmental potential.
详细描述
Infertility affects a significant proportion of reproductive-aged couples worldwide, and female infertility contributes substantially to these cases. Diminished ovarian reserve (DOR) is characterized by reduced quantity and quality of ovarian follicles and is associated with impaired oocyte competence and reduced success rates during assisted reproductive technologies.
Recent evidence highlights the importance of the Hippo signaling pathway in ovarian physiology and folliculogenesis. Yes-Associated Protein 1 (YAP1), a major downstream effector of Hippo signaling, regulates granulosa cell proliferation and survival. Dysregulation of YAP1 and its downstream target Connective Tissue Growth Factor (CTGF) may contribute to abnormal follicular development and ovarian dysfunction.
Non-coding RNAs, including long non-coding RNAs (lncRNAs) and microRNAs (miRNAs), have emerged as important regulators of ovarian function. Nuclear Paraspeckle Assembly Transcript 1 (NEAT1) has been implicated in granulosa cell proliferation and ovarian disorders through its function as a competing endogenous RNA (ceRNA). miR-181a-5p has been shown to regulate cell proliferation and apoptosis and may target YAP1 expression.
This study will investigate the proposed NEAT1/miR-181a-5p/Hippo signaling regulatory axis in women with DOR undergoing IVF treatment. Follicular fluid-derived cells and follicular fluid samples will be analyzed for expression of NEAT1, miR-181a-5p, YAP1, CTGF, and IGF1. Associations between these biomarkers and IVF outcomes will also be evaluated.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 40 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Women undergoing In Vitro Fertilization (IVF) or Intracytoplasmic Sperm Injection (ICSI) cycles.
- •Infertility duration of at least one year
- •Primary or secondary infertility.
排除标准
- •Polycystic Ovary Syndrome (PCOS)
- •Endometriosis.
- •Ovarian tumors or malignancy.
- •Severe systemic diseases affecting fertility.
- •Metabolic syndrome.
- •Connective tissue disorders.
- •Hormonal therapy within the last three months.
- •Refusal to participate.
研究组 & 干预措施
Group 2: DOR Group
Group 2: DOR Group
Women diagnosed with diminished ovarian reserve according to at least two of the following criteria:
Anti-Müllerian Hormone (AMH) ≤1.1 ng/mL
Antral Follicle Count (AFC) ≤7
Basal Follicle-Stimulating Hormone (FSH) ≥10 IU/L
Group 1: Control Group
Group 1: Control Group
Women with normal ovarian reserve undergoing In Vitro Fertilization (IVF) due to non-ovarian causes of infertility such as male factor infertility or tubal factor infertility.
结局指标
主要结局
Expression levels of Nuclear Paraspeckle Assembly Transcript 1 (NEAT1), microRNA-181a-5p (miR-181a-5p), Yes-Associated Protein 1 (YAP1), and Connective Tissue Growth Factor (CTGF).
时间窗: At oocyte retrieval during the participant's IVF cycle (approximately 10-14 days after initiation of controlled ovarian stimulation).
Assessment of gene and protein expression levels in follicular fluid-derived cells from women with Diminished Ovarian Reserve (DOR) compared with controls.
次要结局
- Association With IVF Outcomes(Assessed on the day of oocyte retrieval (approximately 10-14 days after initiation of controlled ovarian stimulation))
- Association With IVF Outcomes(Assessed at blastocyst evaluation, 5-6 days after fertilization)
- Association With IVF Outcomes(Assessed on the day of oocyte retrieval and fertilization assessment (within 0-1 day after oocyte retrieval))
- Association Between NEAT1 and miR-181a-5p Expression(At oocyte retrieval during the participant's IVF cycle (approximately 10-14 days after initiation of controlled ovarian stimulation).)
- Association Between miR-181a-5p and Hippo Pathway Components(At oocyte retrieval during the participant's IVF cycle (approximately 10-14 days after initiation of controlled ovarian stimulation).)
- Insulin-Like Growth Factor 1 (IGF1) Levels in Follicular Fluid(At oocyte retrieval during the participant's IVF cycle (approximately 10-14 days after initiation of controlled ovarian stimulation).)
研究者
Abeer Othman Fahmi Mohammed
Assistant Lecturer of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Assiut University
Assiut University