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Aging and Disease    2017, Vol. 8 Issue (5) : 546-557     DOI: 10.14336/AD.2017.0110
Original Article |
Parity History Determines a Systemic Inflammatory Response to Spread of Ovarian Cancer in Naturally Aged Mice
Ulises Urzua1,4,5,*,Carlos Chacon1,Luis Lizama2,Sebastián Sarmiento1,Pía Villalobos1,Belén Kroxato1,Katherine Marcelain3,5,María-Julieta Gonzalez4
1Laboratorio de Genómica Aplicada, Facultad de Medicina, Universidad de Chile
2Programa de Virología, ICBM
3Programa de Genética Humana, ICBM
4Programa de Biología Celular y Molecular, ICBM
5Departamento de Oncología Básica y Clínica, Facultad de Medicina, Universidad de Chile, Santiago, Chile
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Aging intersects with reproductive senescence in women by promoting a systemic low-grade chronic inflammation that predisposes women to several diseases including ovarian cancer (OC). OC risk at menopause is significantly modified by parity records during prior fertile life. To date, the combined effects of age and parity on the systemic inflammation markers that are particularly relevant to OC initiation and progression at menopause remain largely unknown. Herein, we profiled a panel of circulating cytokines in multiparous versus virgin C57BL/6 female mice at peri-estropausal age and investigated how cytokine levels were modulated by intraperitoneal tumor induction in a syngeneic immunocompetent OC mouse model. Serum FSH, LH and TSH levels increased with age in both groups while prolactin (PRL) was lower in multiparous respect to virgin mice, a finding previously observed in parous women. Serum CCL2, IL-10, IL-5, IL-4, TNF-α, IL1-β and IL-12p70 levels increased with age irrespective of parity status, but were specifically reduced following OC tumor induction only in multiparous mice. Animals developed hemorrhagic ascites and tumor implants in the omental fat band and other intraperitoneal organs by 12 weeks after induction, with multiparous mice showing a significantly extended survival. We conclude that previous parity history counteracts aging-associated systemic inflammation possibly by reducing the immunosuppression that typically allows tumor spread. Results suggest a partial impairment of the M2 shift in tumor-associated macrophages as well as decreased stimulation of regulatory B-cells in aged mice. This long term, tumor-concurrent effect of parity on inflammation markers at menopause would be a contributing factor leading to decreased OC risk.

Keywords age      parity      ovarian cancer      menopause      cytokine      inflammation      mouse model     
Corresponding Authors: Ulises Urzua   
Issue Date: 01 October 2017
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Ulises Urzua
Carlos Chacon
Luis Lizama
Sebastián Sarmiento
Pía Villalobos
Belén Kroxato
Katherine Marcelain
María-Julieta Gonzalez
Cite this article:   
Ulises Urzua,Carlos Chacon,Luis Lizama, et al. Parity History Determines a Systemic Inflammatory Response to Spread of Ovarian Cancer in Naturally Aged Mice[J]. A&D, 2017, 8(5): 546-557.
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