GUSTAVO ARANTES ROSA MACIEL
Projetos de Pesquisa
Unidades Organizacionais
Instituto Central, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/58 - Laboratório de Ginecologia Estrutural e Molecular, Hospital das Clínicas, Faculdade de Medicina
LIM/58 - Laboratório de Ginecologia Estrutural e Molecular, Hospital das Clínicas, Faculdade de Medicina
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- Impact of hormone therapy on the bone density of women with premature ovarian insufficiency: A systematic review(2023) COSTA, Giulia Paiva Oliveira; FERREIRA-FILHO, Edson Santos; SIMOES, Ricardo dos Santos; SOARES-JUNIOR, Jose Maria; BARACAT, Edmund Chada; MACIEL, Gustavo Arantes RosaIntroduction: Women with premature ovarian insufficiency (POI) are exposed to a long period of estrogenic deficiency, which potentially brings higher health risks, especially regarding bone health. We performed a systematic review of the literature to evaluate the effect of hormone therapy (HT) on bone mineral density (BMD) in women with POI.Materials and methods: A systematic search was performed of the MEDLINE and EMBASE databases up to September 2021. We included studies that analyzed women with idiopathic (spontaneous) POI treated with HT, and those who had BMD evaluated. Analysis of risk of bias of studies selected was performed.Results: We found 335 articles and selected 16 studies according to the inclusion criteria. Most of the studies revealed lower bone density in both the femoral neck and lumbar spine of women with POI compared with healthy women. Bone mass had the tendency to remain stable in women treated with estrogen + progestin therapy. However, in women already with bone mass loss, the therapy -in the doses most frequently used -was not able to revert the loss. Higher doses of estrogen seem to have a positive impact on BMD, as did combined oral contraceptives used continuously. Also, the interruption of HT for longer than one year was linked to significant bone loss.Conclusion: Although HT brings clear benefits, further studies are needed to establish its long-term effects, as well as doses and formulations with better protective effects on the bone mass of these women.
- SARS-CoV-2 infection and COVID-19 and human reproduction - A changing perspective - A 2022 update(2023) DELAMUTA, Luciana C.; MONTELEONE, Pedro A. A.; FERREIRA-FILHO, Edson S.; HEINRICH-OLIVEIRA, Vanessa; SOARES-JUNIOR, Jose Maria; BARACAT, Edmund C.; MACIEL, Gustavo Arantes Rosa
- Hormonal and Metabolic Factors Influence the Action of Progesterone on the Endometrium of Women with Polycystic Ovary Syndrome(2023) BARACAT, Maria Candida P.; BARACAT, Edmund C.; SIMOES, Ricardo S.; SIMOES, Manuel J.; MACIEL, Gustavo A. R.; AZZIZ, Ricardo; JR, Jose Maria SoaresHormonal and metabolic factors may influence endometrial quality and interfere with the action of progesterone. Therefore, the aim of our study was to address this issue. Participants were recruited from an outpatient reproductive endocrinology clinic at an academic tertiary medical care centre. All subjects underwent endometrial biopsy (EB) in the follicular phase of the cycle prior to treatment. Thereafter, they were treated with micronized progesterone (400 mg/day x 10 days intravaginally) from days 14-28 of the next cycle. A second EB was performed between days 21-24 of the cycle (the second phase). The metabolic and hormonal serum levels were evaluated during the implantation window. EB samples were analysed using light microscopy for histomorphometric analysis. The endometrium of women with Polycystic Ovarian Syndrome (PCOS) in the second phase demonstrated a uniform surface epithelium with less leukocyte infiltration and an absence of apoptotic figures compared to the control group. (p < 0.021). The thickness of the surface epithelium in the second phase of the PCOS group correlated positively with free and bioavailable testosterone values. The number of stromal cells increases with increasing insulin levels. Our results suggest that histomorphometric abnormalities of the endometrium persist and are linked to androgen and insulin levels despite progesterone supplementation in PCOS.
- Evaluation of circulating microRNA profiles in Brazilian women with polycystic ovary syndrome: A preliminary study(2022) MAFFAZIOLI, Giovana De Nardo; BARACAT, Edmund Chada; SOARES, Jose Maria; CARVALHO, Katia Candido; MACIEL, Gustavo Arantes RosaObjective Polycystic ovary syndrome (PCOS) is a heterogeneous endocrinopathy, which etiology encompasses complex genetic traits associated with epigenetic factors, including differences in microRNA (miRNA) expression in a variety of tissues. The circulating form of these molecules is raising attention in the syndrome not only as potential biomarkers of PCOS but also as possible therapeutic targets. The aim of this study was to explore the circulating miRNA profiles present in a cohort of Brazilian women with and without PCOS and to evaluate the potential role of miRNAs in the pathophysiology of the syndrome. Methods Cross-sectional study of 36 well-characterized PCOS women and 16 healthy controls. Clinical, hormone and metabolic data were recorded and evaluated. The expression profile of the 201 circulating miRNA selected were analyzed by taqman quantitative real time polymerase chain reactions (RT-PCR) using a customized Open Array platform. Statistical and bioinformatic analyzed were performed. Results Circulating miR-21-5p, miR-23a-3p and miR-26a-5p were upregulated, and miR-103a-3p, miR-376a-3p, miR-19b-3p and miR-222-3p were downregulated in women with PCOS compared to healthy normo-ovulatory controls. miR-21-5p, miR-103a-3p and miR-376a-3p levels correlated positively with androgen levels. These miRNAs, in combination, were related to pathways involved in insulin signaling, steroids biosynthesis and endothelial regulation as well as in folliculogenesis. Conclusion In this study, we identified a specific circulating miRNA signature in Brazilian women with PCOS. According to our data, circulating miR-21-5p, miR-23a-3p, miR-26a-5p, miR-103a-3p, miR-376a-3p, miR-19b-3p and miR-222-3p may represent potential candidates for differential diagnosis of PCOS in the future.
- PRL-R Variants Are Not Only Associated With Prolactinomas But Also With Dopamine Agonist Resistance(2023) MOREIRA, Andrea Ramos de Castro; TRARBACH, Ericka; BUENO, Cristina Bellotti Formiga; MONTEIRO, Anna Louise Stellfeld; GRANDE, Isabella Pacetti Pajaro; PADULA, Mario; MACIEL, Gustavo Arantes Rosa; GLEZER, AndreaContext Knockout prolactin receptor gene (PRL-R) mice are animal models for prolactinomas and PRL acts via autocrine/paracrine inhibiting lactotroph proliferation. Recently, variants of the PRL-R were identified in prolactinoma patients and their frequency was higher compared to individuals from the genomic database. Objective We analyzed PRL-R variants frequency in an extensive cohort of prolactinoma patients and evaluated their association with clinical, laboratorial, and imaging characteristics and hormonal response to cabergoline. Design Observational, retrospective, and cross-sectional study. Setting This study took place at the Neuroendocrinology Unit of Clinics Hospital, Medical School of University of Sao Paulo, Brazil, a tertiary referral center. Patients and Methods Study participants included adults with sporadic prolactinomas treated with cabergoline, where response to therapy was defined by prolactin normalization with up to 3 mg/week doses. DNA was extracted from blood samples and the PRL-R was analyzed by polymerase chain reaction techniques and automatic sequencing. The association of PRL-R variants with serum prolactin levels, maximal tumor diameter, tumor parasellar invasiveness, and response to cabergoline was analyzed. Results We found 6 PRL-R variants: p.Ile100(76)Val, p.Ile170(146)Leu, p.Glu400(376)Gln/p.Asn516(492)Ile, p.Glu470Asp e p.Ala591Pro; the last 2 are newly described in prolactinomas' patients. The variants p.Glu400(376)Gln/p.Asn516(492)Ile and p.Ala591Pro were more frequent amongst patients compared to genomic databases, and the p.Asn516(492)Ile showed pathogenic potential using in silico analysis as previously described. PRL-R variants were associated with male sex (P = 0.015), higher serum PRL levels (P = 0.007), larger tumors (P = 0.001), and cabergoline resistance (P < 0.001). Conclusions The prolactin/prolactin receptor system seems to be related to prolactinoma tumorigenesis and cabergoline resistance. Additional studies are needed to better understand the PRL-R variants' role and their potential as therapeutic targets.
- Does bisphenol A (BPA) participates in the pathogenesis of Polycystic Ovary Syndrome (PCOS)?(2023) URBANETZ, Lorena Ana Mercedes Lara; JR, Jose Maria Soares; MACIEL, Gustavo Arantes Rosa; SIMOES, Ricardo dos Santos; BARACAT, Maria Candida Pinheiro; BARACAT, Edmund ChadaPCOS is an endocrine disorder characterized by chronic anovulation, hyperandrogenism, and polycystic ovaries. Its etiology is uncertain. It is debated whether BPA would be a component of the environmental factor in the etiology of PCOS. Contamination by BPA can occur from food packaging (exposure during the diet) and through skin absorption and/or inhalation. It can be transferred to the fetus via the placenta or to the infant via breast milk, and it can be found in follicular fluid, fetal serum, and amniotic fluid. The phenolic structure of BPA allows it to interact with Estrogen Receptors (ERs) through genomic signaling, in which BPA binds to nuclear ER alpha or Er beta, or through nongenomic signaling by binding to membrane ERs, prompting a rapid and intense response. With daily and constant exposure, BPA's tendency to bioaccumulate and its ability to activate nongenomic signaling pathways can alter women's metabolic and reproductive function, leading to hyperandrogenism, insulin resistance, obesity, atherogenic dyslipidemia, chronic inflammatory state, and anovulation and favoring PCOS. The harmful changes caused by BPA can be passed on to future generations without the need for additional exposure because of epigenetic modifications. Not only high BPA levels can produce harmful effects, but at low levels, BPA may be harmful when exposure occurs during the most vulnerable periods, such as the fetal and neonatal periods, as well as during the prepubertal age causing an early accumulation of BPA in the body. Learning how BPA participates in the pathogenesis of PCOS poses a challenge and further studies should be conducted.
- Influence of Phenotypes on the Metabolic Syndrome of Women with Polycystic Ovary Syndrome over a Six-Year Follow-Up in Brazil(2023) JR, Jose Maria Soares; HAYASHIDA, Sylvia Asaka Yamashita; MARCONDES, Jose Antonio Miguel; MACIEL, Gustavo Arantes Rosa; BARCELLOS, Cristiano Roberto Grimaldi; MAFFAZIOLI, Giovana De Nardo; MONTEIRO, Karla Krislaine Alves Costa; TURRI, Jose Antonio Orellana; AZZIZ, Ricardo; BARACAT, Edmund ChadaBackground: We followed polycystic ovary syndrome (PCOS) women with metabolic syndrome (MS) over a six-year treatment period and evaluated the influence of PCOS phenotypes on MS and on the risk for type 2 diabetes mellitus (T2DM). Methods: This was an observational study of 457 PCOS women, whose demographic, clinical, hormonal, and metabolic data underwent analysis. The PCOS women were divided into four groups per NIH recommendations. Results: After a follow-up of a mean of six years (1-20 years), 310 patients were selected to assess the development of T2DM and MS. The clinical and biochemical parameters, along with the Rotterdam phenotypes, were evaluated. Data were analyzed using Student's t- and the Pearson chi-square tests for data variation and group proportions, respectively. Additionally, multivariate analysis was applied to evaluate the effect of PCOS phenotypes on the risk for MS and T2DM. Patients of the four PCOS phenotypes did not differ in age, body mass index, total testosterone, insulin resistance, and dyslipidemia, but phenotype A patients showed the highest risk for T2DM. A decrease in androgen levels was not followed by an improved metabolic profile; instead, there was a significant increase in the number of T2DM cases. Conclusion: Phenotype A women are at the highest risk for type 2 diabetes mellitus.