Extra reproductive effects of melatonin on the genital system and breast

• Grant number: 18/24224-9
• Support Opportunities: Research Projects - Thematic Grants
• Start date: October 01, 2021
• End date: 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: Bruna Salani Mota ; José Cipolla Neto ; Kátia Cândido Carvalho ; LEA TAMI SUZUKI ZUCHELO ; Luciana Lamarão Damous ; Regina Célia Teixeira Gomes
• Associated scholarship(s): 24/04941-9 - The study of the role of melatonin in the carcinogenesis and invasion of invasive ductal breast carcinoma by the evaluation of the immunoexpression MT1 MT2 androgenic receptor ROCK1 ROCK2 and PER2., BP.TT; 23/12681-4 - Standardization of breast adenocarcinoma cells culture (MCF-7 and MDA-MB-231) and the effect of melatonin on migration of these cells induced by prolactin, BP.IC; 22/04174-2 - Effects of melatonin and 17beta-estradiol on the expression profile of microRNAs and their targets in invasive ductal carcinoma of the breast, BP.PD

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)

Scientific publications

(8)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

GLAUCIA MARA MENEZESDASILVA; EDUARDO CARVALHO DE ARRUDA VEIGA; MANUEL JESUS SIMÕES; RICARDO SANTOS SIMÕES; MARCOS EIJI SHIROMA; MARIA CÂNDIDA PINHEIRO BARACAT; GIVANNA SANTOS CAVALCANTI; JOSE MARIA SOARES JUNIOR; EDMUND CHADA BARACAT. Effects of estrogen and raloxifene on synaptic density in the hippocampal CA1 region of ovariectomized rats. Clinics, v. 78, 2024-01-08. (18/24224-9)

BARACAT, MARIA CANDIDA P.; BARACAT, EDMUND C.; SIMOES, RICARDO S.; SIMOES, MANUEL J.; MACIEL, GUSTAVO A. R.; AZZIZ, RICARDO; SOARES JR, JOSE MARIA. Hormonal and Metabolic Factors Influence the Action of Progesterone on the Endometrium of Women with Polycystic Ovary Syndrome. DIAGNOSTICS, v. 13, n. 3, p. 16-pg., 2023-02-01. (18/24224-9)

GIORDANO, LUIZ AUGUSTO; GIORDANO, MARIO VICENTE; TEIXEIRA GOMES, REGINA CELIA; SIMOES, RICARDO DOS SANTOS; PINHEIRO BARACAT, MARIA CANDIDA; GIORDANO, MARIO GASPARE; FERREIRA-FILHO, EDSON SANTOS; DE MEDEIROS, SEBASTIAO FREITAS; BARACAT, EDMUND CHADA; SOARES-JUNIOR, JOSE MARIA. Effects of clinical and metabolic variables and hormones on the expression of immune protein biomarkers in the endometrium of women with polycystic ovary syndrome and normal-cycling controls. Gynecological Endocrinology, v. 38, n. 6, p. 8-pg., 2022-04-08. (18/24224-9)

SEGANFREDO, ISADORA B.; BIANCHI, CRISTINA; TACLA, MARICY; CHEDRAUI, PETER; HADDAD, JORGE M.; SIMOES, RICARDO; BARACAT, EDMUND C.; SOARES JR, JOSE M.. Comparison of promestriene with vaginal fractional CO2 laser and radiofrequency treatments of genitourinary syndrome of menopause. MATURITAS, v. 186, p. 8-pg., 2024-06-12. (18/24224-9)

MONTEIRO, KARLA KRISLANE ALVES COSTA; DAMOUS, LUCIANA LAMARAO; SHIROMA, MARCOS EIJI; TERMINI, LARA; CIPOLLA-NETO, JOSE; SIMOES, RICARDO DOS SANTOS; DA SILVA, RINALDO FLORENCIO; TURRI, JOSE ANTONIO; BARACAT, EDMUND C.; SOARES-JUNIOR, JOSE MARIA. Melatonin increases superoxide dismutase 2 (SOD2) levels and improves rat ovarian graft function after transplantation. JOURNAL OF OVARIAN RESEARCH, v. 17, n. 1, p. 13-pg., 2024-10-16. (18/24224-9, 19/24327-5)

SOARES-JR, J. M.; ESPOSITO SORPRESO, I. C.; NUNES CURADO, J. F.; FERREIRA FILHO, E. S.; DOS SANTOS SIMOES, R.; BONFA, E.; SILVA, C. A.; BARACAT, E. C.. Hormone therapy effect on menopausal systemic lupus erythematosus patients: a systematic review. CLIMACTERIC, v. N/A, p. 7-pg., 2022-04-19. (18/24224-9, 15/03756-4)

GONCALVES, ANA CAROLINA CISESKI; CARVALHO, KATIA CANDIDO; TURRI, JOSE ANTONIO ORELLANA; SIMOES, RICARDO DOS SANTOS; CARVALHO, JESUS PAULA; DA SILVA, LUIZ FERNANDO FERRAZ; SOARES JUNIOR, JOSE MARIA; BARACAT, EDMUND CHADA. 7,12-Dimethylbenz(a)anthracene as a Model for Ovarian Cancer Induction in Rats. BIOLOGY-BASEL, v. 14, n. 1, p. 24-pg., 2025-01-01. (18/24224-9)

MOTA, BRUNA SALANI; REIS, YEDDA NUNES; DE BARROS, NESTOR; CARDOSO, NATALIA PEREIRA; MOTA, ROSA MARIA SALANI; SHIMIZU, CARLOS; TUCUNDUVA, TATIANA CARDOSO DE MELLO; FERREIRA, VERA CHRISTINA CAMARGO DE SIQUEIRA; GONCALVES, RODRIGO; DORIA, MAIRA TEIXEIRA; et al. Effects of preoperative magnetic resonance image on survival rates and surgical planning in breast cancer conservative surgery: randomized controlled trial (BREAST-MRI trial). Breast Cancer Research and Treatment, v. 198, n. 3, p. 15-pg., 2023-02-14. (18/24224-9)