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A novel effect of sulforaphane on promoting mouse granulosa cells proliferation via the NRF2-TKT pathway. | LitMetric

A novel effect of sulforaphane on promoting mouse granulosa cells proliferation via the NRF2-TKT pathway.

J Adv Res

Department of Animal Genetics, Breeding and Reproduction, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, 210095, China. Electronic address:

Published: September 2024

AI Article Synopsis

  • Granulosa cells (GCs) are crucial for follicular development, and while FSH promotes their proliferation, existing superovulation techniques in animal husbandry face challenges such as costs and hormonal issues.
  • This study investigates the potential of sulforaphane (SFN) to enhance GCs proliferation and the mechanisms behind its effects.
  • Findings indicate that SFN functions similarly to FSH by activating the NRF2-TKT pathway, which increases ribose 5-phosphate production, contributing to the necessary nucleotide pool for GCs proliferation.

Article Abstract

Introduction: 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.

Objectives: This study aimed to investigate the effect of sulforaphane (SFN) on ovarian GCs proliferation and the underlying mechanisms.

Methods: 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.

Results: 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.

Conclusion: 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.

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Source
http://dx.doi.org/10.1016/j.jare.2024.09.020DOI Listing

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