Trigonelline activates NRF2 and awakens dormant ovarian follicles to promote pregnancy in aging mice.

Mahboobeh Amoushahi, Emil Hagen Ernst, Anders Heuck, Margit Dueholm, Erik Ernst, Karin Lykke-Hartmann

Department of Biomedicine, Aarhus University, 8000 Aarhus C, Denmark.Department of Biomedicine, Aarhus University, 8000 Aarhus C, Denmark. · pubmed

Paper

Abstract

Aging ovaries exhibit increased oxidative stress, contributing to infertility through cellular and hormonal changes. Nuclear factor E2-related factor 2 (NRF2), a key transcription factor, regulates antioxidant responses. This study investigates NRF2 in dormant (primordial) ovarian follicles to determine if NRF2 activation accounts for primordial follicle activation. We show that trigonelline (TRG) transiently activates NRF2, promoting primordial follicle activation in the non-hormonal phase of follicle development. Indeed, TRG enhances egg quality in aged mice. In human ovarian tissues, TRG increased activation of primordial follicles, resulting in more primary and secondary follicles. Mechanistically, TRG induces NRF2 nuclear translocation and upregulates NRF2-responsive genes, including

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Research summary

Trigonelline activates NRF2 to promote the activation of dormant ovarian follicles in aging mice. This research addresses a mechanism related to reproductive aging, which is a significant aspect of longevity and age-related fertility issues.

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