Zhang Xuan, Zhang Dingding, Fan Aoyun, Zhou Xinyi, Yang Caixia, Zhou Jiaqi, Shen Ming, Liu Honglin, Zou Kang, Tao Jingli
Department of Animal Genetics, Breeding and Reproduction, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, 210095, China.
Department of Animal Genetics, Breeding and Reproduction, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, 210095, China.
J Adv Res. 2025 Aug;74:25-41. doi: 10.1016/j.jare.2024.09.020. Epub 2024 Sep 27.
Granulosa cells (GCs) is essential for maintaining follicular development. Follicle-stimulating Hormone (FSH) has been demonstrated to effectively promote GCs proliferation, driving the establishment of various superovulation techniques for animal husbandry. However, these techniques face challenges, such as high costs, hormonal imbalances, and an increased risk of early ovarian dysfunction. Therefore, it is important to investigate new methods to improve GCs proliferation.
This study aimed to investigate the effect of sulforaphane (SFN) on ovarian GCs proliferation and the underlying mechanisms.
A comparative transcriptomic analysis of ovaries from the control, SFN, and FSH groups was conducted to identify the primary factors contributing to high proliferative capacity. The role of SFN in the regulation of cell proliferation has been examined in mouse ovarian GCs. Gene interference, overexpression, CUT&TAG technology, and transcriptome analyses were performed to elucidate the underlying mechanisms of the nuclear factor E2-related factor 2 (NRF2)-transketolase (TKT) axis in mediating GCs proliferation.
Our research revealed a previously unknown function of SFN, an isothiocyanate of plant origin that is prevalent in cruciferous vegetables, in facilitating the proliferation of mouse ovarian GCs. The efficacy of SFN in enhancing GCs proliferation is similar to that of FSH. At the mechanistic level, SFN promotes NRF2 to transport to the nucleus, which subsequently activates the key enzyme of the non-oxidative pentose phosphate pathway TKT. This activation is instrumental in generating ribose 5-phosphate, a critical precursor for amino acid and nucleotide biosynthesis that underpins the proliferation of GCs.
Collectively, our findings delineate a novel pathway by which SFN, through the NRF2-TKT axis, enhances the nucleotide pool and thereby supports the proliferation of mouse GCs, presenting novel avenues for exploration in reproductive biology and agricultural sciences.
颗粒细胞（GCs）对于维持卵泡发育至关重要。促卵泡激素（FSH）已被证明能有效促进颗粒细胞增殖，推动了畜牧业各种超数排卵技术的建立。然而，这些技术面临着成本高、激素失衡以及卵巢功能早期障碍风险增加等挑战。因此，研究改善颗粒细胞增殖的新方法很重要。
本研究旨在探讨萝卜硫素（SFN）对卵巢颗粒细胞增殖的影响及其潜在机制。
对对照组、SFN组和FSH组的卵巢进行比较转录组分析，以确定导致高增殖能力的主要因素。在小鼠卵巢颗粒细胞中研究了SFN在细胞增殖调节中的作用。进行基因干扰、过表达、CUT&TAG技术和转录组分析，以阐明核因子E2相关因子2（NRF2）-转酮醇酶（TKT）轴在介导颗粒细胞增殖中的潜在机制。
我们的研究揭示了植物源异硫氰酸酯萝卜硫素（在十字花科蔬菜中普遍存在）在促进小鼠卵巢颗粒细胞增殖方面的一种前所未知的功能。SFN增强颗粒细胞增殖的功效与FSH相似。在机制层面，SFN促进NRF2转运至细胞核，随后激活非氧化戊糖磷酸途径的关键酶TKT。这种激活有助于生成5-磷酸核糖，它是氨基酸和核苷酸生物合成的关键前体，为颗粒细胞的增殖提供支持。
总体而言，我们的研究结果描绘了一条新途径，通过该途径SFN通过NRF2-TKT轴增强核苷酸库，从而支持小鼠颗粒细胞的增殖，为生殖生物学和农业科学探索提供了新途径。
