Extra reproductive effects of melatonin on the genital system and breast

• Grant number: 18/24224-9
• Support Opportunities: Research Projects - Thematic Grants
• Duration: October 01, 2021 - September 30, 2026
• Field of knowledge: Health Sciences - Medicine - Maternal and Child Health
• Principal Investigator: José Maria Soares Junior
• Grantee: José Maria Soares Junior
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Pesquisadores principais: Edmund Chada Baracat ; Manuel de Jesus Simões
• Associated researchers: José Cipolla Neto ; LEA TAMI SUZUKI ZUCHELO ; Regina Célia Teixeira Gomes

Abstract

Melatonin is an indolaminergic pineal hormone that plays an important role in the regulation of the cardiovascular, neurological, immune, integumentary, endocrine systems, in particular, metabolism and reproductive processes. In the reproductive system, it is known that melatonin participates in physiological processes from the release of GnRH in the hypothalamus to endometrial receptivity. However, there are still little explored aspects of melatonin that this project aims to explore, such as evaluating the actions of melatonin in proliferation, angiogenesis and apoptosis, as well as in the local immune system and cell survival. Thus, the primary objective that permeates all subprojects of this project is to study the possible non-reproductive actions of melatonin in tissues that are highly influenced by estrogen, such as breast and ovarian tissue. Thus, subproject # 1 aims to understand the role of melatonin in Breast Carcinogenesis in patients with estrogen receptor, while subproject # 2 aims to understand the mechanisms involved in the melatonin role on the action of estrogen (as well as its interaction with other hormones such as prolactin, in both "in vitro" and "in vivo" models. In addition, (subproject # 3), we will verify these functional interactions, in primary cell culture of granulosa cells, where we will study angiogenesis processes and the Hif1± and STAT3, related to tumor growth, cell proliferation and survival. All of this knowledge will be used in subproject # 4 to analyze the impact of melatonin on ovarian graft survival. subprojects that analyze the effects of melatonin on the tissues of the genital and breast systems, especially to assess its antiproliferative, apopotic, angiogenic and antioxidant action. hor understand the mechanisms by which melatonin acts in the growth and dissemination of neoplastic cells. In the third subproject, our objective was to evaluate the interaction of melatonin with estrogen in the intracellular mechanisms of proliferation, angiogenesis and apoptosis in ovarian estrogen-dependent non-tumor cells (granulosa cells). In this way, we can verify if the mechanisms of action are similar in neoplastic and non-neoplastic tissues. Finally, in the subproject #4, our objective is to assess the quality and survival of autologous ovarian tissue transplantation in animals. Also check whether the mechanisms of action of melatonin are similar. These results can be translated to young patients, in the reproductive period, who had Breast Cancer. (AU)