7848 Characterization of vasomotor symptoms-like temperature changes in a mouse model of menopause

Abstract Disclosure: E. Torres Jimenez: None. M. Silva: None. S.T. Zdon: None. V.M. Navarro: None. Most menopausal women suffer vasomotor symptoms (VMS), also known as hot flashes(HFs), induced by the decline in estrogen levels towards the menopausal period. HFs aredescribed as a sudden-onset sensation of extreme warmth, cutaneous vasodilation, sweatingand cold-seeking behavior as part of an inappropriate heat dissipation response to a drop incore temperature. HFs vary in frequency, duration and severity, and can impair the quality oflife of the women affected. These variables change within the same individual throughout theday, indicating that HFs are under the control of yet unknown circadian and ultradian cues.Unfortunately, the field is lacking an experimental mouse model that recapitulates the onsetand progression of VMS during menopause to investigate the neuroendocrine mechanismscontrolling this phenomenon. Here, we used the mouse model of menopause based on theshort-term bilateral removal of the ovaries (ovariectomy, OVX). To monitor core- and skintemperatures (Tc and Tskin, respectively) in response to estrogen loss, we placed temperaturedata loggers (DST-nano probes) in the abdomen of 3-mo female C57BL/6 mice (n=5) for Tcrecordings, and in the ventral surface of the tail for Tskin recordings in the same mouse. Tcand Tskin were recorded simultaneously every 10 min to provide a complete sequence of HFs-like events in the transition from gonad intact (pre-menopause) to short-term OVX (menopause). We observed a continuous fluctuation in Tc and Tskin throughout the dark (ZT12– ZT0) and light (ZT0 – ZT12) phases. Basal, maximum, amplitude and mean temperaturewere monitored on each phase for all mice. Interestingly, temperature changes were observedduring the dark phase, with an increase in the heat loss index (HLI, indirect measurement oftail skin vasodilatation) during week 1 post-OVX. Additionally, during the first week post-OVX,maximum Tskin increased during both dark and light phases. Interestingly, mean Tc decreasedthroughout the two weeks post OVX, leading to a significant shortening of Tc amplitude (i.e.range) post OVX. This decrease in mean Tc in response to OVX was directly correlated withan increase in the mean and amplitude of Tskin (increased heat dissipation), thus replicatinga human VMS. These changes in Tc and Tskin were more evident during the dark phase.Overall, this study supports the use of OVX mice as a model of human VMS. This modelpresents an exacerbation of the temperature fluctuations (VMS) during the dark phase which,despite the species differences in dark/light activity, correlates with the worsening of VMS insome women at night. Finally, the increase in basal temperature during the first week postOVX, but not the second, suggests that the mouse window for menopause-like symptoms isrelatively short post-OVX and by the second week they may resemble a post-menopausalmodel where VMS are less severe. Presentation: 6/2/2024