Mechanisms and effects of AdipoRon, an adiponectin receptor agonist, on ovarian granulosa cells—a systematic review

Lucas Fornari Laurindo, Lívia Fornari Laurindo, Victória Dogani Rodrigues, Eduardo Federighi Baisi Chagas, Jéssica da Silva Camarinha Oliveira, Virgínia Maria Cavallari Strozze Catharin, Sandra Maria Barbalho
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Abstract

Granulosa cells, crucial components of ovarian follicles, play a fundamental role in follicle development, hormone production, and overall reproductive health. These cells are integral to steroidogenesis, including the synthesis and secretion of key hormones such as estrogen and progesterone. Dysregulation of granulosa cells can lead to reproductive disorders, including polycystic ovary syndrome and infertility. This systematic review provides a comprehensive evaluation of AdipoRon, a synthetic agonist of adiponectin receptors AdipoR1 and AdipoR2, and its effects on ovarian function, with a particular focus on granulosa cells. Due to the absence of clinical trials, the review centers on preclinical studies to explore AdipoRon’s potential therapeutic benefits and to suggest future research directions. A detailed literature search across databases such as PubMed, Scopus, Web of Science, Embase, and Google Scholar was conducted using terms related to AdipoRon and ovarian function. The review encompasses four preclinical studies involving various models: primary granulosa cells from rats, laying hens’ granulosa cells, human luteinized granulosa cells, and chicken ovary follicles. Findings indicate that AdipoRon enhances glucose absorption in rat granulosa cells by stimulating glucose transporter 1 expression, modulates steroid hormone secretion in laying hens’ granulosa cells, and affects cell proliferation and steroidogenesis in human luteinized granulosa cells. Additionally, AdipoRon, in conjunction with recombinant chicken adiponectin, influences ovarian follicular cell proliferation and steroidogenesis in chicken ovary follicles. This review highlights the need for further investigation into AdipoRon’s long-term effects and its potential applications in reproductive health and therapy.

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脂肪素受体激动剂 AdipoRon 对卵巢颗粒细胞的作用机制和影响--系统综述
颗粒细胞是卵巢卵泡的重要组成部分,在卵泡发育、激素分泌和整体生殖健康中发挥着重要作用。这些细胞是类固醇生成不可或缺的组成部分,包括合成和分泌雌激素和孕酮等关键激素。颗粒细胞失调可导致生殖系统疾病,包括多囊卵巢综合症和不孕症。本系统综述全面评估了AdipoRon(一种脂肪直通素受体AdipoR1和AdipoR2的合成激动剂)及其对卵巢功能的影响,尤其关注颗粒细胞。由于缺乏临床试验,本综述以临床前研究为中心,探讨 AdipoRon 的潜在治疗功效,并提出未来的研究方向。我们使用与 AdipoRon 和卵巢功能相关的术语在 PubMed、Scopus、Web of Science、Embase 和 Google Scholar 等数据库中进行了详细的文献检索。综述包括四项临床前研究,涉及不同的模型:大鼠原始颗粒细胞、蛋鸡颗粒细胞、人类黄体化颗粒细胞和鸡卵巢滤泡。研究结果表明,AdipoRon 可通过刺激葡萄糖转运体 1 的表达来增强大鼠颗粒细胞对葡萄糖的吸收,调节蛋鸡颗粒细胞的类固醇激素分泌,并影响人类黄体化颗粒细胞的细胞增殖和类固醇生成。此外,AdipoRon 与重组鸡脂肪连通素一起可影响鸡卵巢滤泡细胞的增殖和类固醇生成。这篇综述强调了进一步研究 AdipoRon 的长期效应及其在生殖健康和治疗中的潜在应用的必要性。
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