http://www.bdtd.uerj.br/handle/1/3555 2026-09-08T19:09:23Z http://www.bdtd.uerj.br/handle/1/25572 Título: Influência da suplementação de ômega 3 durante a gestação e seu impacto na placenta: revisão integrativa experimental e clínica Autor: Vieira, Cristiane Bastos Leta Primeiro orientador: Thole, Alessandra Alves Abstract: The placenta is a temporary and multifunctional organ, essential for healthy fetal development, acting as a vital metabolic, endocrine, and immunological interface for the exchange of nutrients, gases, and hormones between the mother and the conceptus. Recognizing its vulnerability to stressors, supplementation with omega 3 polyunsaturated fatty acids (PUFAs) emerges as a nutritional strategy to improve maternal-fetal health and, primarily, placental homeostasis. This thesis investigates the influence of omega 3 fatty acid supplementation during pregnancy and its impact on placental pathophysiology, integrating findings from experimental studies with rodents and clinical trials in humans. The methodology consists of an integrative literature review, based on the framework of Whittemore; Knafl and Kutcher; LeBaron using the PubMed, LILACS, and Cochrane Library databases. The search was guided by the PICO question: Does omega 3 supplementation, compared to the absence of supplementation, promote structural and functional improvements in the placenta? Twenty-four studies were included, of which 16 used animal models and 8 were RCTs. In studies with animal models, omega 3 has consistently demonstrated high efficacy, being associated with the activation of peroxisome proliferator-activated receptor gamma (PPARG), a central mechanism that regulates lipid transport (via FATP4 and CD36) and placental bioenergy. Furthermore, omega 3 has been described as a powerful anti-inflammatory and antioxidant axis, providing pro-resolution mediators (such as resolvins and protectins) and increasing the activity of enzymes such as SOD, GPx, and catalase, essential for maintaining technical integrity and perfusion. In stark contrast, scientific clinical trials in humans have demonstrated evidence of low clinical reliability, marked by high risk of death (RoB2), heterogeneous results, and, critically, failure to confirm that essential molecular targets were achieved in pregnant women, which explains the weakness of the clinical evidence. The study concludes that omega 3 supplementation has the potential to specifically modulate placental biology, as consistently evidenced in experimental models through the optimization of lipid transport and the resolution of inflammation. However, in the clinical trials studied, the current evidence remains inconclusive and does not allow for a universal assertion that supplementation improved placental composition and health. This thesis points to important gaps that need to be investigated so that omega 3 can be used for placental health. The translational divergence reveals that the clinical efficacy of omega 3 depends on overcoming methodological flaws and transitioning to an isolation nutrition paradigm, based on the genetic and metabolic stratification of pregnant women. Instituição: Universidade do Estado do Rio de Janeiro Tipo do documento: Tese 2026-02-12T00:00:00Z http://www.bdtd.uerj.br/handle/1/25438 Título: Integração tireoide, inflamação e sarcopenia na Doença Renal Crônica Autor: Reis, Karina Schiavoni Scandelai Cardoso Primeiro orientador: Tavares, Ana Beatriz Winter Abstract: Thyroid dysfunction is common in chronic kidney disease (CKD) and tends to worsen with declining glomerular filtration rate (GFR), being modulated by factors such as proteinuria, malnutrition, and inflammation. In patients undergoing hemodialysis (HD), these disturbances amplify alterations in the thyroid–nutrition–muscle axis, which are associated with increased cardiovascular risk and mortality, despite the limited integrated evidence available addressing these mechanisms in this population. In this cross-sectional study, we investigated the association between thyroid function and CKD progression across different stages, analyzing its relationship with proteinuria and GFR in stages 3 and 4, as well as its interrelationships with nutritional status, inflammation, and sarcopenia in HD patients, in addition to developing a predictive model for identifying the risk of sarcopenia. The first article assessed the correlation between thyroid function and proteinuria in CKD stages 3 and 4. A total of 150 patients were included, 64 (42.6%) in stage 3 and 86 (59.3%) in stage 4, with a median age of 68 years (IQR 61–76). Median thyroid stimulating hormone (TSH), free T4 (FT4), and urinary protein-creatinine ratio (PCR) were 2.9 IU/mL (IQR 1.89–4.04), 1.26 ng/dL (IQR 1.10–1.41), and 315.5 mg/g (IQR 108.3–830), respectively. Proteinuria was detected in 91 patients (60.6%). There was a positive correlation between PCR and TSH (r = 0.23; p = 0.003) and a negative correlation between PCR and FT4 (r = –0.17; p = 0.03), suggesting that urinary protein loss may affect thyroid hormone metabolism. However, no significant differences in thyroid function were found between stages 3 and 4. The second article investigated the relationship among thyroid function, nutritional status, sarcopenia, and inflammation in 101 HD patients and 33 controls. The median age was higher in HD patients compared to controls (58 vs. 48 years, respectively). Thyroid autoimmunity was less prevalent in HD (6.9%) than in controls (18.1%). Compared with controls, HD patients exhibited higher TSH, C-reactive protein, interleukin-6, tumor necrosis factor α, and leptin levels, and lower FT3, FT4, albumin, and Geriatric Nutritional Risk Index (GNRI) values (p < 0.05), with no difference in BMI. Handgrip strength, skeletal muscle mass, and skeletal muscle mass index were significantly lower in HD patients. Sarcopenia was more frequent in HD patients (48.5% probable; 26.7% confirmed) than in controls (18.1% and 6%). Within the HD group, sarcopenic individuals showed significantly lower FT3 levels. A penalized regression model (Elastic Net) identified four independent predictors of sarcopenia: FT3, TSH, GNRI and dialysis status. Each 1 mIU/L increase in TSH raised the probability of sarcopenia by 6.6% (OR ≈ 1.07), while each 1 pg/mL increase in FT3 reduced the risk by 18% (OR ≈ 0.82). GNRI had a modest protective effect, and HD status increased the odds by 47% (OR ≈ 1.47). In summary, HD patients exhibit thyroid dysfunction, heightened inflammation, and poor nutritional status conditions closely associated with sarcopenia. FT3, TSH, GNRI and being on HD emerge as integrated risk markers for sarcopenia, underscoring the need for a multidimensional clinical approach targeting the thyroid–nutrition–muscle axis. Instituição: Universidade do Estado do Rio de Janeiro Tipo do documento: Tese 2025-12-04T00:00:00Z http://www.bdtd.uerj.br/handle/1/25334 Título: Potencial terapêutico sexo-dependente da oxitocina em modelos de dependência da nicotina em camundongos adolescentes Autor: Dias, Rodrigo Araujo Cocêlo Primeiro orientador: Carvalho, Anderson Ribeiro Abstract: The number of smokers worldwide has decreased in recent years, being relatively higher among males. However, the tobacco industry has increasingly invested in the modernization of electronic cigarettes (e-cigarettes). Nicotine is the main component present in cigarette smoke, responsible for causing chemical dependence among tobacco users. It influences the mesocorticolimbic dopaminergic reward system and the extended amygdala system. Since the adolescent brain has not yet fully developed all its structures and neural connections, susceptibility to nicotine is greater during this period. Several therapies have been proposed for smoking cessation; however, given their limitations and side effects, new therapeutic targets need to be investigated. Previous studies have shown that the neuropeptide oxytocin (OXT) has the ability to mitigate dependence induced by drugs of abuse. In this context, the present study aims to investigate the effect of OXT administration on behavioral responses associated with nicotine dependence in adolescent mice. To this end, we evaluated the effectiveness of intranasal administration of this neuropeptide on nicotine’s ability to induce behavioral sensitization using the open field test (OF), on anxiety levels after drug withdrawal using the elevated plus maze test (EPM), and on nicotine’s ability to induce conditioning using the conditioned place preference test (CPP). Adolescent male and female Swiss mice were used in this study. These animals were tested on postnatal day 30 (PN30) and postnatal day 40 (PN40) using the OF and EPM tests, respectively, over a 12-day period, referred to as subproject 1. They received intranasal administration of OXT (100 µg/kg) 1 hour before the OF test and an intraperitoneal (i.p.) injection of nicotine (0.5 mg/kg). In the EPM test, they were not exposed to any drugs, i.e., they underwent a 48-hour drug-free period. The animals were also tested on PN30 using the CPP test, referred to as subproject 2. The nicotine and OXT doses used in this test were the same as those used in the OF test. Results showed that nicotine induces behavioral sensitization, which was reversed by OXT administration in females. There were no significant effects or interactions between the drugs regarding anxiety in mice. Nicotine also induced place conditioning; however, this effect was not altered by OXT administration. OXT appears to be a promising molecule for smoking cessation, showing potential in pharmacological therapies by interfering with nicotine’s rewarding properties. Nevertheless, the effects of this neuropeptide are sex-dependent and vary according to the life stage in which it is self-administered. Further studies are needed to clarify the mechanisms underlying OXT’s action in nicotine-induced dependence. Instituição: Universidade do Estado do Rio de Janeiro Tipo do documento: Tese 2025-11-18T00:00:00Z http://www.bdtd.uerj.br/handle/1/24909 Título: Perfil dos hormônios tireoidianos em mulheres durante o tratamento de reprodução assistida (fertilização in vitro) e a gestação Autor: Oliveira, Yuri Ian Lima Alves de Primeiro orientador: Tavares, Ana Beatriz Winter Abstract: Thyroid dysfunction is common among women of reproductive age and can affect fertility and pregnancy outcomes. The detectability of thyroid autoantibodies in this population had not been previously studied. Data on ovarian stimulation (OS) and in vitro fertilization (IVF) in the context of thyroid function are heterogeneous and inconsistent. This study aimed to assess whether thyroid function varies significantly during OS and IVF cycles involving frozen embryo transfer (FET) up to the end of the first trimester, and whether detectability—not just positivity—of thyroid autoantibodies correlates with ovarian reserve in women treated at a fertility clinic. We evaluated 453 women undergoing OS to investigate associations between thyroid autoantibodies and ovarian reserve, assessed via anti-Müllerian hormone (AMH) levels and antral follicle count (AFC). Anti-thyroid peroxidase antibody (TPOAb) and antithyroglobulin antibody (TgAb) were categorized as undetectable, minimally, moderately detectable, or positive. 24.4% of participants had at least one positive antibody. Most patients had detectable autoantibodies at low levels (42.3% for TPOAb and 66.9% for TgAb), but no statistically significant differences were found between antibody levels and ovarian reserve (AMH < or ≥ 1.1 ng/mL; AFC < or ≥ 7 follicles). TSH levels did not show correlation with ovarian reserve markers. In a prospective study, 275 euthyroid women were monitored for changes in TSH, free T4, and total T4 during OS, IVF, and early pregnancy. Participants received recombinant FSH/LH and progesterone for pituitary suppression, followed by GnRH agonist for final maturation and total embryo freezing. Thyroid function was assessed at seven time points, from OS initiation to 90 days post-embryo transfer. A transient TSH increase was observed after OS (1.47±0.47 to 1.82±0.79 mIU/L; p=0.001), peaking at pregnancy confirmation (1.86±0.74 mIU/L), with only 2.8% exceeding 4.0 mIU/L. Baseline and first-trimester TSH levels were similar (1.47±0.47 vs. 1.36±0.61 mIU/L; p=0.108). Free and total T4 levels did not correlate with TSH. Thyroid autoantibody prevalence was low—TPOAb (4.9%), TgAb (1.7%), both (2.9%)—with no significant effect on TSH or pregnancy outcomes. In conclusion, thyroid autoantibodies were not associated with ovarian reserve. Despite transient fluctuations in thyroid function during OS and early pregnancy, TSH levels did not demonstrate difference at the end of the first trimester compared to baseline. Given the TSH peak at pregnancy confirmation, TSH should be assessed before OS, at pregnancy confirmation in "freeze-all" cycles, and at the end of the first trimester. Instituição: Universidade do Estado do Rio de Janeiro Tipo do documento: Tese 2025-08-05T00:00:00Z