Abstract
Researchers have long assumed that systematic estrogen fading might contribute to the sustained progression of menopausal degenerate syndromes, although definitive evidence has not been presented. Whether such findings represent a causal contribution or are the result of opportunistic messengers sent from the reproductive system to the brain is also a vital question. We constructed a multiscale network of the ovariectomy (OVX) induced estrogen receptors depletion (ER-depletion) model and integrated targeted proteomic, targeted lipidomic, cytochemical, and histopathological data across three tissues from the ovariectomy rodent model. We found that compared to control rats, OVX rats showed increased renal and uterine prostaglandin D2 synthase (Ptgds) expression and decreased hypothalamic Ptgds expression, abnormal Ptgds metabolites, the degenerate renal function profiles and decreased cognitive ability (learning and memory) in Morris water maze test. Importantly, we observed a regulatory relationship among ER (particularly ERβ), the degree of the pathological phenotype, learning behavior test and the ‘hypothalamus-uterus-kidney (HUK) axis functions. Collectively, this study elucidates that ER depletion promoted HUK aging is mostly attributed to a renal ERβ/Ptgds signalling imbalance.
Highlights
Female ageing begins with the ageing of the reproductive system, which drives primordial follicular ovarian pools to accelerate consumption
Urinary and serum eicosanoid disturbances reflect lipid metabolism disorder Eicosanoids in arachidonic acid metabolism are key metabolites in the aetiology of metabolic syndrome (MetS), we investigated whether the eicosanoid perturbation in rats with ovarian failure was due to the estrogen receptors (ER)-depletion and defects in renal absorption
We further investigated whether the fluctuation of eicosanoid dynamics was due to prostaglandin D2 synthase (Ptgds) overexpression that suffered from ER-depletion
Summary
Female ageing begins with the ageing of the reproductive system, which drives primordial follicular ovarian pools to accelerate consumption. Accompanied by estrogen depletion and turbulence, menopausal ovarian failure is the final step in this process [1]. An inevitable stage of ageing among 45~55-year-old women, is a complex process involving a variety of cellular and molecular changes. Menopause has been described to have different “appearances”; the main physiological manifestations are ovary fading and suffering from various phenotypic syndromes, such as hot flashes, anxiety, insomnia, depression, osteoporosis, and cognitive decline [2]. In addition to the typical symptoms of these menopausal syndromes, there is a symptom of rapid ageing. The emergence of rapid ageing is partially due to age, and rapid ageing has a very important relationship with the loss of estrogen in menopause
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