Microcystin-LR disrupts ovarian granulosa cell glycolysis via GSK3β-Mediated HK2 mitochondrial dissociation: Evidence from integrated In Vivo and In Vitro models

IF 2.8 4区医学 Q2 REPRODUCTIVE BIOLOGY

Reproductive toxicology Pub Date : 2025-08-09 DOI:10.1016/j.reprotox.2025.109028

Jintao Yuan , Xinrui Li , Songci Yan , Chengyu Luo , Sijia Xian , Yuanyuan Li , Jiang Wu

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引用次数: 0

Abstract

Reproductive disorders, a significant global health challenge, impact roughly 10 % of couples of reproductive ages. Notably, among these couples, 60–70 % of reproductive disorders are associated with women. Current evidence highlights that glycolysis plays an essential role in female reproductive function and is critical to follicle development and maturation. Microcystins (MCs), monocyclic heptapeptide toxins produced by freshwater cyanobacteria, include various isomers. Among them, microcystin-leucine-arginine (MC-LR) is the most prevalent and toxic form and is commonly found in water and food sources. However, the precise effects of MC-LR on glycolysis and its underlying mechanisms remain poorly understood. Therefore, this study aims to explore whether MC-LR induces reproductive defects in female mammals by disrupting glycolysis in human ovarian granulosa cells and mouse ovarian tissue, and to clarify its underlying mechanism.

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微囊藻毒素lr通过gsk3 β介导的HK2线粒体解离破坏卵巢颗粒细胞糖酵解：来自体内和体外综合模型的证据

生殖疾病是一项重大的全球健康挑战，影响着大约10%的育龄夫妇。值得注意的是，在这些夫妇中，60%至70%的生殖障碍与妇女有关。目前的证据表明，糖酵解在女性生殖功能中起着至关重要的作用，对卵泡的发育和成熟至关重要。微囊藻毒素（MCs）是淡水蓝藻产生的单环七肽毒素，包括各种异构体。其中，微胱氨酸-亮氨酸-精氨酸（MC-LR）是最普遍和毒性最大的形式，通常存在于水和食物中。然而，MC-LR对糖酵解的确切影响及其潜在机制仍然知之甚少。因此，本研究旨在探讨MC-LR是否通过破坏人卵巢颗粒细胞和小鼠卵巢组织的糖酵解诱导雌性哺乳动物生殖缺陷，并阐明其潜在机制。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Reproductive toxicology 生物-毒理学

CiteScore

6.50

自引率

3.00%

发文量

131

审稿时长

45 days

期刊介绍： Drawing from a large number of disciplines, Reproductive Toxicology publishes timely, original research on the influence of chemical and physical agents on reproduction. Written by and for obstetricians, pediatricians, embryologists, teratologists, geneticists, toxicologists, andrologists, and others interested in detecting potential reproductive hazards, the journal is a forum for communication among researchers and practitioners. Articles focus on the application of in vitro, animal and clinical research to the practice of clinical medicine. All aspects of reproduction are within the scope of Reproductive Toxicology, including the formation and maturation of male and female gametes, sexual function, the events surrounding the fusion of gametes and the development of the fertilized ovum, nourishment and transport of the conceptus within the genital tract, implantation, embryogenesis, intrauterine growth, placentation and placental function, parturition, lactation and neonatal survival. Adverse reproductive effects in males will be considered as significant as adverse effects occurring in females. To provide a balanced presentation of approaches, equal emphasis will be given to clinical and animal or in vitro work. Typical end points that will be studied by contributors include infertility, sexual dysfunction, spontaneous abortion, malformations, abnormal histogenesis, stillbirth, intrauterine growth retardation, prematurity, behavioral abnormalities, and perinatal mortality.