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Orthotopic Ovarian Transplantation Procedures to Investigate the Life- and Health-span Influence of Ovarian Senescence in Female Mice
Published on: February 12, 2018
Ovariectomy shortens the life span of female mice
Valeria Benedusi1, Elisa Martini2, Marinos Kallikourdis2,3
1Center of Excellence on Neurodegenerative Diseases and Department of Pharmacological and Biomolecular Sciences, University of Milan, 20133, Milan, Italy.
Abstract:
This study shows that lack of ovarian activity has a negative impact on the life span of female mice. The extent to which this phenomenon could be associated with the anti-inflammatory effect of estrogens was analyzed in metabolic organs and aorta, by quantitative analysis of mRNAs encoding proteins in the inflammatory cascade. We demonstrate that the TNFα, IL-1β, MCP-1, MIP-2 and IL-6 mRNA contents are increased in the liver, adipose tissue and aorta 7 months after ovariectomy (ovx) and this increased basal inflammation is maintained as the mice aged. In contrast, the extent of inflammatory gene expression is directly proportional to age in sham-operated mice. As a consequence, at 22 months, most of the inflammatory parameters examined were higher in the sham-operated group compared with the ovx group. These observations led us to propose that the decreased longevity of ovx mice may be due to an acceleration of the basal state of inflammation in metabolic organs, which is likely driven by the combination of a lack of estrogen-mediated anti-inflammatory activity and the loss of gonadal control of energy metabolism.
Insights
Ovarian activity loss shortens female mice lifespan by increasing inflammation in metabolic organs. Estrogen
Area of Science:
- Reproductive biology
- Immunology
- Gerontology
Background:
- Ovarian activity is crucial for female health and longevity.
- Estrogens possess anti-inflammatory properties that may influence lifespan.
- The impact of ovarian senescence on systemic inflammation is not fully understood.
Purpose of the Study:
- To investigate the relationship between ovarian activity, inflammation, and lifespan in female mice.
- To determine the role of estrogen deficiency in age-related inflammatory changes.
- To analyze inflammatory gene expression in metabolic organs and aorta following ovariectomy.
Main Methods:
- Quantitative analysis of mRNA encoding inflammatory proteins.
- Comparison of ovariectomized (ovx) and sham-operated female mice.
- Assessment of inflammatory markers in liver, adipose tissue, and aorta at different ages.
Main Results:
- Ovariectomy led to increased TNFα, IL-1β, MCP-1, MIP-2, and IL-6 mRNA in liver, adipose tissue, and aorta.
- This elevated basal inflammation in ovx mice persisted with aging.
- Sham-operated mice showed age-dependent increases in inflammation, surpassing ovx levels later in life.
Conclusions:
- Reduced ovarian activity accelerates basal inflammation in metabolic organs, contributing to decreased longevity in female mice.
- The loss of estrogen's anti-inflammatory effect and gonadal control of metabolism likely drives this accelerated inflammation.
- These findings highlight the critical role of ovarian function in maintaining metabolic homeostasis and promoting healthy aging.
