Humanized Mouse Models as a Cellular Platform for Investigating Immune-Hormonal Crosstalk and Therapeutic Strategies...

Menopause is a complex biological transition marked by the decline of ovarian function and estrogen levels, leading to a wide range of physiological and immunological changes in women. Traditional animal models, particularly ovariectomized rodents, have been instrumental in studying menopause; however, they often fail to fully replicate human hormonal and immune responses. Humanized mouse models, which incorporate human immune systems and tissues, represent a promising alternative for bridging this translational gap. This review explores the current applications of humanized mice in disease research and highlights their untapped potential in menopause studies. We discuss the limitations of existing menopause models and propose a novel framework for using humanized mice to investigate estrogen signaling, immune interactions, and functional food interventions. Functional foods such as soy isoflavones, polyphenols, omega-3 fatty acids, and probiotics have shown beneficial effects on menopausal symptoms in clinical and animal studies, yet their immune-modulatory mechanisms remain underexplored in human-relevant models. We advocate for interdisciplinary collaboration to develop and utilize humanized mouse models tailored to menopause research. This integrated approach may offer new insights into the immune-hormonal landscape of menopause and pave the way for personalized, non-invasive therapeutic strategies.