NATALIA GARCIA
Projetos de Pesquisa
Unidades Organizacionais
LIM/58 - Laboratório de Ginecologia Estrutural e Molecular, Hospital das Clínicas, Faculdade de Medicina
8 resultados
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conferenceObject Melatonin action on luteal - granulosa cells in women with marital infertility undergoing in vitro fertilization(2016) MAGANHIN, Carla; CARVALHO, Katia; TURCO, Edson Lo; SERAFINI, Paulo; GARCIA, Natalia; CIPOLLA-NETTO, Jose; SIMOES, Manuel; BARACAT, Edmund; SOARES-JUNIOR, Jose Maria- Differences in neonatal exposure to estradiol or testosterone on ovarian function and hormonal levels(2015) MARCONDES, Rodrigo R.; CARVALHO, Katia C.; DUARTE, Daniele C.; GARCIA, Natalia; AMARAL, Vinicius C.; SIMOES, Manuel J.; TURCO, Edson G. Lo; SOARES JR., Jose M.; BARACAT, Edmund C.; MACIEL, Gustavo A. R.Exposure to an excess of androgen or estrogen can induce changes in reproductive function in adult animals that resemble polycystic ovary syndrome in humans. However, considerable differences exist among several types of animal models. Little is known about the molecular features of steroidogenesis and folliculogenesis in the ovaries of rats exposed to different sex steroids as neonates. Here, we evaluated the impact of androgen and estrogen exposure on the ovaries of adult female rats during their neonatal period in the gene expression of Lhr and Cyp17a1, two key players of steroidogenesis. We also assessed hormone levels, folliculogenesis and the theca-interstitial cell population. The study was performed on the second postnatal day in thirty female Wistar rats that were sorted into the following three intervention groups: testosterone, estradiol and vehicle (control group). The animals were euthanized 90 days after birth. The main outcomes were hormone serum levels, ovary histomorphometry and gene expression of Lhr and Cyp17a1 as analyzed via quantitative real-time PCR. We found that exposure to excess testosterone in early life increased the LH and testosterone serum levels, the LH/FSH ratio, ovarian theca-interstitial area and gene expression of Lhr and Cyp17a1 in adult rats. Estrogen induced an increase in the ovarian theca-interstitial area, the secondary follicle population and gene expression of Lhr and Cyp17a1. All animals exposed to the sex steroids presented with closed vaginas. Our data suggest that testosterone resulted in more pronounced reproductive changes than did estrogen exposure. Our results might provide some insight into the role of different hormones on reproductive development and on the heterogeneity of clinical manifestations of conditions such as polycystic ovary syndrome.
bookPart Sarcoma uterino(2014) CARVALHO, Kátia Candido; GARCIA, Natália; JúNIOR, José Maria Soares; MACIEL, Gustavo Arantes Rosa; BARACAT, Edmund Chada- Hypothalamic transcriptional expression of the kis-speptin system and sex steroid receptors differs among polycystic ovary syndrome rat models with different endocrine phenotypes(2017) MARCONDES, Rodrigo Rodrigues; CARVALHO, Katia Candido; GIANNOCCO, Gisele; DUARTE, Daniele Coelho; GARCIA, Natalia; SOARES-JUNIOR, Jose Maria; SILVA, Ismael Dale Cotrim Guerreiro da; MALIQUEO, Manuel; BARACAT, Edmund Chada; MACIEL, Gustavo Arantes RosaOBJECTIVES: Polycystic ovary syndrome is a heterogeneous endocrine disorder that affects reproductive-age women. The mechanisms underlying the endocrine heterogeneity and neuroendocrinology of polycystic ovary syndrome are still unclear. In this study, we investigated the expression of the kisspeptin system and gonadotropin-releasing hormone pulse regulators in the hypothalamus as well as factors related to luteinizing hormone secretion in the pituitary of polycystic ovary syndrome rat models induced by testosterone or estradiol. METHODS: A single injection of testosterone propionate (1.25 mg) (n= 10) or estradiol benzoate (0.5 mg) (n= 10) was administered to female rats at 2 days of age to induce experimental polycystic ovary syndrome. Controls were injected with a vehicle (n= 10). Animals were euthanized at 90-94 days of age, and the hypothalamus and pituitary gland were used for gene expression analysis. RESULTS: Rats exposed to testosterone exhibited increased transcriptional expression of the androgen receptor and estrogen receptor-b and reduced expression of kisspeptin in the hypothalamus. However, rats exposed to estradiol did not show any significant changes in hormone levels relative to controls but exhibited hypothalamic downregulation of kisspeptin, tachykinin 3 and estrogen receptor-a genes and upregulation of the gene that encodes the kisspeptin receptor. CONCLUSIONS: Testosterone-and estradiol-exposed rats with different endocrine phenotypes showed differential transcriptional expression of members of the kisspeptin system and sex steroid receptors in the hypothalamus. These differences might account for the different endocrine phenotypes found in testosteroneand estradiol-induced polycystic ovary syndrome rats.
- May Sonic Hedgehog proteins be markers for malignancy in uterine smooth muscle tumors?(2016) GARCIA, Natalia; BOZZINI, Nilo; BAIOCCHI, Glauco; CUNHA, Isabela Werneck da; MACIEL, Gustavo Arantes; SOARES JUNIOR, Jose Maria; SOARES, Fernando Augusto; BARACAT, Edmund Chada; CARVALHO, Katia CandidoSeveral studies have demonstrated that the Sonic Hedgehog signaling pathway (SHH) plays an important role in tumorigenesis and cellular differentiation. We analyzed the protein expression of SHH pathway components and evaluated whether their profile could be useful for the diagnosis, prognosis, or prediction of the risk of malignancy for uterine smooth muscle tumors (USMTs). A total of 176 samples (20 myometrium, 119 variants of leiomyoma, and 37 leiomyosarcoma) were evaluated for the protein expression of the SHH signaling components, HHIP1 (SHH inhibitor), and BMP4 (SHE target) by immunohistochemistry. Western blot analysis was performed to verify the specificity of the antibodies. We grouped leiomyoma samples into conventional leiomyomas and unusual leiomyomas that comprise atypical, cellular, mitotically active leiomyomas and uterine smooth muscle tumors of uncertain malignant potential. Immunohistochemical analysis showed that SMO, SUFU, GLIL GLI3, and BMP4 expression gradually increased depending on to the histologic tissue type. The protein expression of SMO, SUFU, and GLI1 was increased in unusual leiomyoma and leiomyosarcoma samples compared to normal myometrium. The inhibitor HHIP1 showed higher expression in myometrium, whereas only negative or basal expression of SMO, SUFU, GLIL and GLI3 was detected in these samples. Strong expression of SHE was associated with poorer overall survival. Our data suggest that the expression of SHH proteins can be useful for evaluating the potential risk of malignancy for USMTs. Moreover, GLI1 and SMO may serve as future therapeutic targets for women with USMTs.
- Impaired branched-chain amino acid metabolism may underlie the nonalcoholic fatty liver disease-like pathology of neonatal testosterone-treated female rats(2017) ANZAI, Alvaro; MARCONDES, Rodrigo R.; GONCALVES, Thiago H.; CARVALHO, Katia C.; SIMOES, Manuel J.; GARCIA, Natalia; SOARES JR., Jose M.; PADMANABHAN, Vasantha; BARACAT, Edmund C.; SILVA, Ismael D. C. G. da; MACIEL, Gustavo A. R.Polycystic ovary syndrome (PCOS) is frequently associated with non-alcoholic fatty liver disease (NAFLD), but the mechanisms involved in the development of NAFLD in PCOS are not well known. We investigated histological changes and metabolomic profile in the liver of rat models of PCOS phenotype induced by testosterone or estradiol. Two-day old female rats received sc injections of 1.25 mg testosterone propionate (Testos; n = 10), 0.5 mg estradiol benzoate (E2; n = 10), or vehicle (control group, CNT; n = 10). Animals were euthanized at 90-94 d of age and the liver was harvested for histological and metabolomic analyses. Findings showed only Testos group exhibited fatty liver morphology and higher levels of ketogenic and branched-chain amino acids (BCAA). Enrichment analysis showed effects of testosterone on BCAA degradation pathway and mitochondrial enzymes related to BCAA metabolism. Testos group also had a decreased liver fatty acid elongase 2 (ELOVL2) activity. E2 group had reduced lipid and acylcarnitine metabolites in the liver. Both groups had increased organic cation transporters (SLC22A4 and SLC16A9) activity. These findings indicate that neonatal testosterone treatment, but not estradiol, produces histological changes in female rat liver that mimic NAFLD with testosterone-treated rats showing impaired BCAA metabolism and dysfunctions in ELOVL2, SLC22A4 and SLC16A9 activity.
conferenceObject Transcriptional Expression of Genes Related to Histone Modification in the Hypothalamus of Female Rats Submitted to Neonatal Exposure to Sex Steroids(2014) MARCONDES, Rodrigo Rodrigues; CARVALHO, Katia Candido; GARCIA, Natalia; DUARTE, Daniele Coelho; SOARES JR., Jose Maria; COSTA, Leonardo Tomiatti; AMARAL, Vinicius Cestari; GIANNOCCO, Gisele; BARACAT, Edmund Chada; MACIEL, Gustavo Arantes R.conferenceObject Are the inhibin beta A(bA) under influence of melatonin treatment in the ovary of pinealectomized rats?(2016) MAGANHIN, Carla; CARVALHO, Katia; SASSO, Gisela; SIMOES, Manuel; GARCIA, Natalia; BARACAT, Edmund; SOARES JUNIOR, Jose Maria