ER-depletion lowering the 'hypothalamus-uterus-kidney' axis functions by perturbing the renal ERβ/Ptgds signalling pathway.

For the lipid profile, increasing trends for the levels of TC, TGs, and LDL were observed, while a decreasing trend was observed for the HDL level in the OVX group ( Figure 3E , Supplementary Table 12 ).

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‘Gene-to-Gene’ correlation analysis showed a highly significant negative correlation between uterine ERβ and urine Ptgds, indicating that renal Ptgds overexpression caused by ovarian failure is mainly regulated by ERβ.

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However, we observed an obvious decreasing trend for Ptgds-regulated metabolites in serum and an increasing trend in urine, indicating that these metabolites cannot enter the cardiovascular system through intercellular transfer and that the cell membrane lost its delivery function ( Figure 5 ).

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