Maternal behavior and urinary bladder cancer: implications of hormonal axes modulation and steroid receptors in the pathophysiology of neoplastic lesions

• Grant number: 14/14930-2
• Support Opportunities: Regular Research Grants
• Start date: July 01, 2015
• End date: December 31, 2017
• Field of knowledge: Health Sciences - Medicine - Maternal and Child Health
• Principal Investigator: Wilson de Mello Junior
• Grantee: Wilson de Mello Junior
• Host Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil
• Associated researchers: Wagner José Fávaro

Abstract

The urinary bladder carcinoma is the most prevalent type of cancer in the human urinary tract, with high morbidity and mortality. Men are three to four times more likely to develop the urinary bladder cancer, but it is women who have more aggressive tumors and lower life expectancy. The development of bladder cancer has been associated with sex steroid hormones and stress response. The early-life experiences epigenetically modulate the responses of the hypothalamic-pituitary-adrenal (HPA) and hypothalamic-pituitary-gonadal (HPG) axis in rats, primates and humans. In rats, these experiences are directly related to the maternal care received by the neonate in the postnatal period. The manipulation of maternal care in rodents generates permanent modulation in those hormonal axes. It is believed that these changes lead to various metabolic disorders which favor the onset and progression of many diseases, including cancer. However, the role of steroid receptor expression on bladder tumors is not clear. This project aims to examine the effects of both brief and prolonged maternal separation during the early-life on the urinary bladder cancer development in adulthood. The development of bladder tumors, chemically induced by MNU, will be evaluated by histopathology, immunohistochemistry, Western blotting and serum analysis in different experimental groups: Brief Maternal Separation (BMS) - 15 minutes - resulting in increased maternal care and attenuated responses of the HPA axis in adults; Prolonged maternal separation (PMS) - 4 hours -, resulting in decreased maternal care and hyperresponsiveness of the HPA axis in adults; and Control (C), when there is no separation between mother and offspring. (AU)