Investigation of endocannabinoid 2-AG and its hydrolases for regulation on sperm motility and acrosome reaction in Kunming mice.

IF 2.1

Reproduction, fertility, and development Pub Date : 2026-02-19 DOI:10.1071/RD25040

Xin Zhang, Wenjing Wu, Yahui Li, Minghua Yang

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Abstract

Context: A key endocannabinoid, 2-arachidonoyl glycerol (2-AG), regulates sperm hyperactivation in humans via alpha/beta hydrolase domain-containing protein 2 (ABHD2)-mediated CatSper calcium channel activation. However, the role of ABHD2 in mice is unclear, whereas monoacylglycerol lipase (MAGL), ABHD-containing protein 6 (ABHD6), and ABHD-containing protein 12 (ABHD12) modulate 2-AG in the mouse central nervous system (CNS).

Aims: This study explored the impact of 2-AG on mouse sperm motility, its regulatory mechanisms, and the involvement of MAGL, ABHD6, and ABHD12.

Methods: 2-AG concentrations in caput and caudal epididymal sperm from Kunming mice were quantified. ABHD2/6/12 and MAGL were identified, localized, and assessed for roles in motility and calcium (Ca2+) influx.

Key results: Caput sperm exhibited higher 2-AG contents than did caudal sperm. Four hydrolases regulated motility via 2-AG hydrolysis to induce calcium influx. MAGL showed the strongest hydrolytic activity, ABHD2 the weakest. Subcellular localization showed MAGL in mid-piece, ABHD12 in mid-piece and principal piece, and ABHD2/ABHD6 in acrosomal region.

Conclusions: 2-AG modulates mouse sperm motility via calcium signaling. MAGL, ABHD6, and ABHD12 drive 2-AG hydrolysis, while ABHD2 is linked to acrosome exocytosis, not 2-AG breakdown.

Implications: Targeting MAGL/ABHD12 offers non-hormonal contraceptive strategies or assisted reproductive technology (ART) improvements. Monitoring 2-AG and hydrolase activity could aid in diagnosing male infertility.

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内源性大麻素2-AG及其水解酶对昆明小鼠精子活力和顶体反应调控的研究。

2- ag（2-花生四烯醇甘油）是一种关键的内源性大麻素，通过ABHD2 （α / β水解酶结构域蛋白2）介导的CatSper钙通道激活来调节人类精子的过度激活。然而，ABHD2在小鼠中的作用尚不清楚，而MAGL（单酰基甘油脂肪酶）、ABHD6 （α / β水解酶结构域蛋白6）和ABHD12 （α / β水解酶结构域蛋白12）调节小鼠中枢神经系统中的2-AG。本研究探讨2-AG对小鼠精子活力的影响及其调控机制，以及MAGL、ABHD6和ABHD12的参与。方法测定昆明小鼠附睾精子头部和尾部2-花生四烯醇甘油含量。ABHD2/6/12 （α / β水解酶结构域蛋白2/6/12）和MAGL（单酰基甘油脂肪酶）被鉴定、定位并评估其在运动和Ca 2 +流入中的作用。头端精子的2-AG水平高于尾端精子。四种水解酶通过2-AG水解来调节运动，诱导钙内流。MAGL水解活性最强，ABHD2最弱。亚细胞定位显示，MAGL位于中段，ABHD12位于中段和主段，ABHD2/ABHD6位于顶体区。结论2-AG通过钙信号调节小鼠精子活力。MAGL、ABHD6和ABHD12驱动2-AG水解，而ABHD2与顶体胞分泌有关，而与2-AG分解无关。针对MAGL/ABHD12提供非激素避孕策略或ART改进。监测2-AG和水解酶活性有助于诊断男性不育症。

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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Reproduction, fertility, and development

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