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Hyperandrogenism is a determining diagnostic factor for PCOS. If pregnancy is conceived, it is considered high-risk due to several potential complications, but the correlation between pre-pregnancy androgen levels and obstetric outcomes is poorly characterized. OBJECTIVE: To determine if pre-pregnancy serum androgen concentrations and androgen indexes differed when certain obstetric and neonatal outcomes appeared in PCOS. METHODS: A single-center, retrospective study was carried out. All patients were treated between 2012 and 2019. A total of 73 patients had all the endocrine and obstetric data available. Pre-pregnancy hormone levels (total testosterone-T, androstenedione-AD, DHEAS (dehydroepiandrosterone sulfate), SHBG (sex-hormone-binding globulin), and TSH (thyroid-stimulating hormone) were collected, and T/SHBG, AD/SHBG, DHEAS/SHBG, T/AD indexes were calculated and compared. RESULTS: When miscarriage was present in the history, significantly elevated pre-pregnancy AD levels were observed. Higher pre-pregnancy AD level was noted in PCOS patients delivering female newborns as compared to males. Additionally, a higher T/AD ratio was associated with subsequent preterm delivery, but significance was lost after age adjustment. Maternal age at delivery had a significant negative correlation with pre-pregnancy DHEAS levels and DHEAS/SHBG ratio. Pre-pregnancy SHBG displayed a significant negative correlation, while pre-pregnancy androgen/SHBG ratios exhibited positive correlations with both birth weight and birth weight percentile. CONCLUSIONS: Based on our data, AD and the T/AD ratio emerge as distinctive factors in certain outcomes, implying a potential specific role of altered 17-ß-HSD (17ß-hydroxysteroid dehydrogenase) enzyme activity, possibly influencing offspring outcomes. The pre-pregnancy T/SHBG ratio exhibits a potentially stronger correlation with fetal growth potential compared to SHBG alone. DHEAS and maternal age at delivery are strongly correlated in PCOS patients.
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Environmental pollutants capable of interfering with the thyroid hormone (TH) system increasingly raise concern for both human and environmental health. Recently, resorcinol has received attention as a compound of concern due to its endocrine disrupting properties. It is a known inhibitor of thyroperoxidase (TPO), an enzyme required in TH synthesis, and therapeutic use of resorcinol exposure has led to hypothyroidism in humans. There is limited evidence concerning ecotoxicologically relevant effects of resorcinol in fish. A set of adverse outcome pathways (AOPs) has recently been developed linking thyroid hormone system disruption (THSD) to impaired swim bladder inflation and eye development in fish. In the present study, these AOPs were used to provide the background for testing potential THSD effects of resorcinol in zebrafish eleutheroembryos. We exposed zebrafish eleutheroembryos to resorcinol and assessed TH levels, swim bladder inflation and eye morphology. As a TPO inhibitor, resorcinol is expected to affect TH levels and eye morphology but not swim bladder inflation during embryonic development. Indeed, thyroxine (T4) levels were significantly decreased following resorcinol exposure. In contrast to our hypothesis, swim bladder inflation was impaired at 5 days post fertilization (dpf) and no effects on eye morphology were detected. Therefore, in vitro assays were performed to identify potential additional thyroid hormone system disruption-related mechanisms through which resorcinol may act. Two new mechanisms were identified: TH receptor (TR) antagonism and transthyretin (TTR) binding inhibition. Both of these mechanisms can plausibly be linked to impaired swim bladder inflation and could, therefore, explain the observed effect. Overall, our study contributes to the knowledge of the THSD potential of resorcinol both in vivo in the zebrafish model as well as in vitro.
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Disruptores Endócrinos , Resorcinóis , Hormônios Tireóideos , Peixe-Zebra , Animais , Resorcinóis/toxicidade , Disruptores Endócrinos/toxicidade , Hormônios Tireóideos/metabolismo , Poluentes Químicos da Água/toxicidade , Sacos Aéreos/efeitos dos fármacos , Olho/efeitos dos fármacos , Embrião não Mamífero/efeitos dos fármacos , TiroxinaRESUMO
Background/Objective: Infertility affects an estimated 40-50% of women with polycystic ovary syndrome (PCOS), the leading cause of anovulatory infertility, but only a small proportion of the patients require in vitro fertilization (IVF) therapy. Both PCOS and IVF are associated with an increased risk of obstetric complications. To compare preconception endocrine profiles and symptoms, as well as obstetric outcomes of PCOS patients who achieved successful pregnancies with and without IVF treatment. Methods: A single-center retrospective cohort study was conducted. Data spanning from 2012 to 2019 were compiled from patients with PCOS who visited the Gynecologic Endocrinology Unit and the Infertility Unit at the Department of Obstetrics and Gynecology, University of Debrecen. Patients diagnosed with PCOS who had had at least one successful delivery beyond the 23rd gestational week at the department were eligible for inclusion in the study. Results: Fifteen percent of the 206 pregnancies leading to successful deliveries of 232 newborns in our cohort conceived with IVF. A one year increase in the maternal age increased the odds of being in the IVF group by 22% (OR: 1.222, 95% confidence interval, CI: 1.11-1.35, p < 0.001). Baseline DHEAS and androstenedione levels were significantly lower in the IVF group as compared to the non-IVF group: 1 µmol/L increase in the DHEAS level decreased the odds of being in the IVF group by 18% (OR: 0.82, 95% CI: 0.66-1.01, p = 0.06), and 1 µg/L increase in the serum androstenedione concentration decreased the same odds by 42% (OR: 0.58, 95% CI: 0.33-1.02, p = 0.056). DHEAS levels <6.5 µmol/L had an OR 3.86 (95% CI 1.10-13.50, p = 0.04) and LH/FSH ratio <1.3 had an OR 3.58 (95% CI 1.18-10.81, p = 0.03) for being in the IVF group. The birth weight (3069 ± 683 g vs. 3362 ± 638 g, p = 0.02) and the gestational age (37.23 ± 2.55 vs. 38.54 ± 2.28 weeks, p = 0.004) were significantly lower in the IVF group, but in the singleton subgroups, no significant differences could be found. Birth weight percentiles showed no significant difference in either subgroup. In the IVF group, both preterm delivery (29% vs. 8.3%, OR 4.53, 95% CI 1.75-11.70, p = 0.002; singleton subgroup: 17.4% vs. 6.3%, OR 3.12, 95% CI 0.89-10.92, p = 0.07) and cesarean section (71% vs. 43.2%, OR 3.22, 95% CI 1.40-7.40, p = 0.006; singleton subgroup: 65.2% vs. 42.4%, OR 2.55, 95% CI 1.02-6.35, p = 0.04) were more frequent than in the non-IVF group. Gestational diabetes and preeclampsia were not significantly different in the IVF and non-IVF groups. Conclusions: In PCOS patients with successful pregnancies, those who conceive with IVF seem to be different in their baseline hormone levels and symptoms from the non-IVF group. Adverse obstetric outcomes are more common in the IVF group, and some of these differences persist when adjusting for singleton pregnancies and maternal age, too.
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PURPOSE: The aim of this study was to assess the accuracy and diagnostic use of shear wave elastography (SWE) in differentiating central precocious puberty (CPP) with breast development and to analyze the correlations between sex hormone levels and SWE parameters. METHODS: A total of 227 participants were included in this retrospective case-control study, including 113 girls with genuine precocious puberty breast development (the CPP group) and 114 with non-genuine precocious puberty breast development (the non-CPP group). The participants underwent clinical assessment, hormonal assays, and SWE using advanced ultrasound equipment. Statistical analyses, including t-tests, correlation analysis, logistic regression, and receiver operating characteristic (ROC) analysis, were performed to evaluate the diagnostic value of SWE and sex hormone levels in differentiating CPP with breast development. RESULTS: There were no significant differences in clinical characteristics between the two groups. The sex hormone levels of estradiol, testosterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH), and prolactin in the CPP group were significantly higher than those in the non-CPP group. Shear wave velocity (SWV) Maximum (Max), SWV Minimum (Min), SWV Mean, SWV standard deviation (SD), and SWV coefficient of variation in the CPP group were significantly higher than in the non-CPP group. Correlation analysis demonstrated significant positive correlations between LH, FSH, estradiol, and testosterone levels with various SWE parameters, indicating their clinical relevance. Logistic regression analysis identified substantial predictive potential of sex hormone levels and SWE parameters for genuine precocious puberty breast development. Additionally, the ROC analysis highlighted a high predictive value of the combined model of SWE parameters, with an area under the curve (AUC) of 0.903. CONCLUSION: The study underscores the correlations between sex hormone levels and SWE parameters. The superior predictive performance of the combined model of SWE parameters emphasizes the value of integrated SWE assessments for improving the accuracy of diagnosing genuine precocious puberty breast development.
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Progestins are crucial steroid hormones that have attracted wide attention due to their endocrine disrupting effects in fish. The aim of this study is to investigate the effects of long-term exposure to low concentrations of norgestrel (NGT) on the reproductive and thyroid endocrine systems of adult zebrafish. Adult zebrafish were exposed to 7 and 39 ng/L NGT for a duration of 90 days. The results revealed that exposure to 39 ng/L NGT led to a significant up-regulation of 3ß-hydroxysteroid dehydrogenase (hsd3b) and 20ß-hydroxysteroid dehydrogenase (hsd20b) genes in the ovary of female zebrafish. Additionally, there was a significant up-regulation of 11ß-hydroxysteroid dehydrogenase 2 (hsd11b2) gene in the testis of male zebrafish. Furthermore, egg production decreased significantly, accompanied by notable alterations in the proportion of ovarian development stages, as well as reductions of sex hormone levels (E2, 11-KT, and T) in both females and males. However, long-term exposure to low concentrations of NGT did not lead to changes in thyroid hormone levels and thyroid histopathology in adult zebrafish. The overall results imply that environmental concentrations of NGT have a strong endocrine disrupting effect on the reproductive system of zebrafish, while the thyroid system is not sensitive to NGT exposure. The present study underscores the reproductive endocrine impacts of NGT and emphasizes the necessity for prolonged exposure at environmental concentrations.
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The objective was to conduct a systematic review to clarify the effects of l-arginine supplementation in pregnant and lactating sows on plasma hormone levels, milk production and composition, the body condition of sows and piglet performance. In April 2023, an online search and a systematic search were performed in the following databases: Embase, Scopus, SciELO, Web of Science, PubMed and Science Direct. The combinations of keywords used were sow and arginine and lactation; sow and arginine and lactating; sow and arginine and gestation; sow and arginine and gestating; sow and arginine and pregnancy; sow and arginine and reproduction; piglet and arginine; and sow and arginine and mammary gland. In total, 21 scientific articles with original data were selected according to preestablished criteria. Among the 21 articles, seven (33%) reported measurements of some plasma hormones, and among these, six reported an increase in the levels of at least one hormone, namely, estradiol, insulin-like growth factor 1 (IGF-1), insulin, follicle stimulating hormone, growth hormone or prolactin, with l-arginine supplementation. The parameters of milk were evaluated in 11 studies (52%), one reported an increase in protein content, and one reported an increase in IGF-1 content in milk with supplementation of this amino acid. Of the 14 studies that evaluated the performance parameters of piglets, only four reported improvements in some parameters of piglets from sows that received supplementation. Dietary supplementation of arginine for sows in the final third of gestation and/or lactation may alter the plasma levels of some hormones, which may reflect in greater development of the mammary gland tissue and, consequently, promote benefits on the performance of piglets. However, more studies are needed to evaluate the real impact of this amino acid supplementation on the physiology of the sows, in general, and the performance of suckling piglets.
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PURPOSE: Gendered domestic violence and coercive control are prevalent public heath concerns in Canada with dire consequences for survivors. Peer support groups may address and reduce negative impacts of domestic violence and coercive control on women's stress, coping, safety, and alliances with social support network members, the focus of this study. METHODS: A one-group, pre-test/post-test quasi-experimental study was undertaken to evaluate the effectiveness of Growth Circle, a 14-week peer support program offered at an agency serving women affected by domestic violence in a major western Canadian city. Through convenience sampling, women 18 years and older who experienced domestic violence were recruited and provided data on stress, coping, safety-related empowerment, and social support/alliances. Thirty-five participants provided all pre-test and post-test data, with a subsample of 14 providing repeated hair samples. Hair was employed to determine stress hormone (cortisol) levels. RESULTS: A significant reduction in self-reported levels of perceived stress and stress hormone levels following completion of the Growth Circle program was revealed. Participants also reported a significant increase in safety-related empowerment, and supportive alliances with group members. CONCLUSIONS: The Growth Circle peer support program was demonstrated to be effective. Further implementation and research into the Growth Circle program across Canada is recommended.
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Adaptação Psicológica , Violência Doméstica , Hidrocortisona , Grupo Associado , Humanos , Feminino , Hidrocortisona/análise , Hidrocortisona/metabolismo , Adulto , Violência Doméstica/psicologia , Apoio Social , Pessoa de Meia-Idade , Canadá , CoerçãoRESUMO
BACKGROUND: The relationship between thyroid hormone (TH) levels in vivo and osteoarthritis (OA) remains inconclusive. This study aims to investigate the association between TH levels and OA, analyze the effect of triiodothyronine on hypertrophic chondrocyte differentiation and OA progression, and identify potential target genes of triiodothyronine in OA to evaluate its diagnostic value. METHODS: Two-sample mendelian randomization method was used to probe the causal links between hyperthyroidism and OA. Differentially expressed genes (DEGs) from two RNA-sequencing data in Gene Expression Omnibus (GSE199847 and GSE114007) and enrichment analysis of DEGs (166 commonly upregulated genes and 71 commonly downregulated genes of GSE199847 and GSE114007) was performed to analyze the effect of triiodothyronine (T3) on hypertrophic chondrocyte differentiation and OA. C28/I2 cells treated with T3 and reverse transcription and quantitative real-time polymerase chain reaction were used to validate T3 targeted genes. The diagnostic performance of target genes was assessed by the receiver operating characteristic (ROC) curve and area under the curve (AUC). RESULTS: There was a positive causal association between hyperthyroidism and OA (IVW result, OR = 1.330, 95% CI 1.136-1.557, P = 0.0004). Weighted median and Weighted mode analysis also demonstrated that hyperthyroidism had a positive causal association with OA (p < 0.05, OR > 1). Bioinformatics analysis indicated T3 can partially induce the emergence of late hypertrophic chondrocyte and promote OA through extracellular matrix organization, blood vessel development, skeletal system development and ossification. Post-T3 treatment, MAFB, C1QTNF1, COL3A1 and ANGPTL2 were significantly elevated in C28/I2 cells. ROC curves in GSE114007 showed that AUC of all above genes were ≥ 0.7. CONCLUSIONS: This study identified that hyperthyroidism has a positive causal association with OA by MR analysis. T3 induced hypertrophic chondrocytes promote OA progression by upregulating genes such as MAFB, C1QTNF1, COL3A1 and ANGPTL2, which can also serve as OA diagnosis.
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Hipertireoidismo , Análise da Randomização Mendeliana , Osteoartrite , Análise de Sequência de RNA , Tri-Iodotironina , Análise da Randomização Mendeliana/métodos , Osteoartrite/genética , Humanos , Hipertireoidismo/genética , Hipertireoidismo/complicações , Tri-Iodotironina/sangue , Análise de Sequência de RNA/métodos , Condrócitos/metabolismo , Diferenciação Celular/genética , Progressão da DoençaRESUMO
The queen is the sole reproductive individual and the maturing brood replenishes the shorter-lived worker bees. Production of many crops relies on both pesticides and bee pollination to improve crop quantity and quality. Despite the certain knowledge on chemical pesticides caused damage to worker bee physiology and behavior, our understanding of the relationship between honeybee queen development and chemical pesticides remains weak. Here, we comprehensive investigate the effects of the widely used insecticide chlorantraniliprole on the growth, hormone levels, and detoxifying enzyme activity of queen larvae. It has been determined that chlorantraniliprole present a chronic toxic effect on queen larvae and also reduced the fitness of queen, and that these effects are positively correlated with pesticide levels. It has been found that queen larvae began to show reduced capping and emergence rates when exposed to 2 ng/larva of chlorantraniliprole. At 20 ng/larva, queen capping and emergence rates were the lowest, and there were significant reductions in larval hormone level. Chlorantraniliprole have an effect on detoxification enzyme activity and hormone levels in queen larvae. In conclusion, chlorantraniliprole can adversely affect the growth and development of queen larvae. Our findings may guide the scientifically sound use of chemical pesticides to reduce potential risks to queen larvae.
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Inseticidas , Larva , ortoaminobenzoatos , Animais , ortoaminobenzoatos/toxicidade , Larva/efeitos dos fármacos , Inseticidas/toxicidade , Abelhas/efeitos dos fármacos , Abelhas/crescimento & desenvolvimento , FemininoRESUMO
BACKGROUND: Ovarian stimulation and the use of human chorionic gonadotropin (hCG) for triggering oocyte maturation in women undergoing in vitro fertilisation (IVF) introduces several differences in luteal phase hormone levels compared with natural cycles that may negatively impact on endometrial receptivity and pregnancy rates after fresh embryo transfer. Exogenous luteal phase support is given to overcome these issues. The suitability of a pragmatic approach to luteal phase support is not known due to a lack of data on early phase luteal hormone levels and their association with fertility outcomes during IVF with fresh embryo transfer. This study determined early luteal phase profiles of serum progesterone, 17-hydroxyprogesterone and hCG, and associations between hormone levels/hormone level profile after hCG trigger and the live birth rate in women undergoing IVF with fresh embryo transfer. METHODS: This prospective single center, cohort study was conducted in Vietnam from January 2021 to December 2022. Women aged 18-38 years with normal ovarian reserve and undergoing controlled ovarian stimulation using a gonadotropin-releasing hormone antagonist protocol were included. Serum hormone levels were determined before trigger, at 12, 24 and 36 h after hCG, and daily from 1 to 6 days after oocyte pick-up. Serum hormone level profiles were classified as lower or upper. The primary outcome was live birth rate based on early luteal phase hormone level profile. RESULTS: Ninety-five women were enrolled. Live birth occurred in 19/69 women (27.5%) with a lower progesterone profile and 13/22 (59.1%) with an upper progesterone profile (risk ratio [RR] 2.15; 95% confidence interval [CI] 1.28-3.60), and in 6/31 (19.4%) versus 26/60 (43.3%) with a lower versus upper serum 17-hydroxyprogesterone profile (RR 2.24; 95% CI 1.03-4.86). Nearly 20% of women had peak progesterone concentration on or before day 3 after oocyte pick-up, and this was associated with significantly lower chances of having a life birth. CONCLUSIONS: These data show the importance of proper corpus luteum function with sufficient progesterone/17-hydroxyprogesterone production for achievement of pregnancy and to maximize the chance of live birth during IVF. TRIAL REGISTRATION: NCT04693624 ( www. CLINICALTRIALS: gov ).
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Gonadotropina Coriônica , Fertilização in vitro , Fase Luteal , Indução da Ovulação , Progesterona , Humanos , Feminino , Fase Luteal/sangue , Fase Luteal/fisiologia , Fertilização in vitro/métodos , Adulto , Gravidez , Estudos Prospectivos , Progesterona/sangue , Gonadotropina Coriônica/administração & dosagem , Indução da Ovulação/métodos , Taxa de Gravidez , Adulto Jovem , 17-alfa-Hidroxiprogesterona/sangue , Estudos de Coortes , Transferência Embrionária/métodos , Adolescente , Coeficiente de Natalidade , Resultado do Tratamento , Nascido Vivo/epidemiologiaRESUMO
Paracetamol is suggested to have endocrine disrupting properties possibly affecting fetal programming of reproductive health that might lead to impaired semen quality and changes in reproductive hormones. In this longitudinal study, we included 1058 young adult men born 1998-2000 into the Danish National Birth Cohort with follow-up at 18-21 years of age. The exposure, maternal intake of paracetamol, was modelled in three ways: dichotomized, trimester-specific, and as duration of exposure categorized into: short (1-2 weeks), medium (3-9 weeks) or long duration (>9 weeks) vs. no intake. Outcomes included semen characteristics, self-measured testis volume, and reproductive hormone levels. We used negative binominal regression to estimate the percentage difference and 95% confidence interval (CI) for each outcome. In total, 547 (48%) sons were prenatally exposed to paracetamol due to maternal intake at least once. Maternal intake of paracetamol during pregnancy was not associated with any of the biomarkers in the dichotomized or trimester-specific exposure models. For duration of exposure, sons of mothers with long duration of maternal intake of paracetamol showed tendencies towards lower semen concentration (-14% [95% CI: -31%; 8%]), a higher proportion of nonprogressive and immotile spermatozoa (8% [95% CI: -4%; 21%]) and higher DNA Fragmentation Index (16% [95% CI: -1%; 36%]) compared to son of mothers with no intake. Maternal intake of paracetamol during pregnancy was not clearly associated with biomarkers of male fecundity in adult sons. However, it cannot be ruled out that long duration of maternal intake of paracetamol might be associated with impaired semen characteristics.
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Acetaminofen , Analgésicos não Narcóticos , Biomarcadores , Fertilidade , Efeitos Tardios da Exposição Pré-Natal , Humanos , Masculino , Feminino , Gravidez , Adulto Jovem , Biomarcadores/sangue , Adolescente , Fertilidade/efeitos dos fármacos , Estudos Longitudinais , Dinamarca , Testículo/efeitos dos fármacos , Análise do SêmenRESUMO
BACKGROUND: Internet addiction disorder (IAD) is characterized by an excess of uncontrolled preoccupations, urges, or behaviors related to computer use and Internet access that culminate in negative outcomes or individual distress. PIU includes excessive online activities (such as video gaming, social media use, streaming, pornography viewing, and shopping). The aim of this study was to analyze the association of gene polymorphisms that may influence the severity of risky behaviors in young men with the frequency of Internet use. We speculate that there are individual differences in the mechanisms of Internet addiction and that gene-hormone associations may represent useful biomarkers for subgroups of individuals. MATERIALS AND METHODS: The study was conducted in a sample of 407 adult males. Subjects were asked to complete the Problematic Internet Use Test (PIUT). Serum was analyzed to determine concentrations of luteinizing hormone (LH), follicle stimulating hormone (FSH), testosterone (TT), sex hormone binding protein (SHBG), dehydroepiandrosterone sulfate (DHEA-S), estradiol (E2), prolactin (PRL), insulin (I), serotonin (5-HT), and dopamine (DA), as well as DRD2, ANKK1, and NTRK3 gene polymorphisms. RESULTS: In the analysis of the ANKK1 gene, there was a specific association between ANKK1 polymorphisms and PRL and 5-HT blood concentrations. There was also an association between the ANKK1 polymorphisms and LH and DA concentrations. When analyzing the DRD2 gene polymorphism, we found that in the group with a moderate level of Internet dependence, there was an association between both the G/GG and GG/GG polymorphisms and FSH concentration. CONCLUSIONS: Our study found that there may be an association between the NTRK3 gene polymorphism and PIU. The polymorphisms of ANKK1 and DRD2 genes may be factors that influence the concentrations of hormones (PRL, 5-HT, DA) that are associated with the results obtained in PIU.
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Uso da Internet , Serotonina , Masculino , Adulto , Humanos , Genótipo , Polimorfismo de Nucleotídeo Único , Receptores de Dopamina D2/genética , Proteínas Serina-Treonina Quinases/genética , Hormônio Foliculoestimulante/genéticaRESUMO
BACKGROUND: Fluoride exposure may increase the risk of hypothyroidism, but results from previous studies are inconsistent at low-level fluoride exposure (i.e., ≤0.7 mg/L). Human studies of fluoride and thyroid hormone levels in pregnancy are scarce. OBJECTIVES: We examined associations between fluoride exposure and maternal thyroid hormone levels in a Canadian pregnancy cohort, with consideration for fetal sex-specific effects. METHODS: We measured fluoride concentrations in drinking water and spot urine samples collected during each trimester from 1876 pregnant women enrolled in the Maternal-Infant Research on Environmental Chemicals (MIREC) study. We also measured maternal thyroid stimulating hormone (TSH), free thyroxine (FT4), and total thyroxine (TT4) levels during the first trimester of pregnancy. We used linear and non-linear regression models to estimate associations between fluoride exposure and levels of TSH, FT4, and TT4. We explored effect modification by fetal sex and considered maternal iodine status as a potential confounder. RESULTS: A 1 mg/L increase in urinary fluoride was associated with a 0.30 (95 %CI: 0.08, 0.51) logarithmic unit (i.e., 35.0 %) increase in TSH among women pregnant with females, but not males (B = 0.02; 95 %CI: -0.16, 0.19). Relative to women with urinary fluoride concentrations in the first quartile (0.05-0.32 mg/L), those with levels in the third quartile (0.49-0.75 mg/L) had higher FT4 and TT4 (i.e., inverted J-shaped associations), but the association was not statistically significant after adjustment for covariates (p = 0.06). Water fluoride concentration showed a U-shaped association with maternal FT4, whereby women with water fluoride concentrations in the second (0.13-0.52 mg/L) and third (0.52-0.62 mg/L) quartiles had significantly lower FT4 compared to those with levels in the first quartile (0.04-0.13 mg/L). Adjustment for maternal iodine status did not change the results. DISCUSSION: Fluoride exposure was associated with alterations in maternal thyroid hormone levels, the magnitude of which appeared to vary by fetal sex. Given the importance of maternal thyroid hormones for fetal neurodevelopment, replication of findings is warranted.
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Iodo , Tiroxina , Masculino , Feminino , Humanos , Gravidez , Fluoretos/efeitos adversos , Canadá , Hormônios Tireóideos , Tireotropina , ÁguaRESUMO
Thyroid hormone in the hypothalamus acts as a key determinant of seasonal transitions. Thyroid hormone-levels in the brain are mainly regulated by the hypothalamic tanycytes and pituitary pars tuberalis (PT)-specific cells. TSHß produced by the PT-specific cells stimulates Dio2 expression and decreases Dio3 expression of the tanycytes. Both tanycytes and PT-specific cells in photosensitive animals exhibit remarkable changes of morphological appearance and expressions of genes and proteins under different photoperiods. Long photoperiods induce increased gene- and protein-expressions and active features. Short photoperiods cause the decreased gene- and protein-expressions and inactive features. In the PT, expressions of TSHß, common α-subunit of glycoprotein hormones (α-GSU), and MT1 receptor of melatonin receptors and eyes absent 3 change under different photoperiods. Diurnal rhythms of α-GSU mRNA expression are observed in the PT of Djungarian hamsters. Hes1, Nkx2.1, and LIM homeodomain gene 2 (Lhx2) are involved in the differentiation of PT. In the hypothalamic tanycytes, expressions of Dio2, Dio3, vimentin, serine/threonine kinase 33, GPR50, Nestin, Retinoid signaling genes (retinaldehyde dehydrogenase 1, cellular retinol binding protein 1, and Stra6), monocarboxylate transporter 8, and neural cell adhesion molecule change under different photoperiods. Rax, Lhx2, Nfia/b/x, and fibroblast growth factor 10 are involved in the differentiation of tanycytes.
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Células Ependimogliais , Fotoperíodo , Cricetinae , Animais , Proteínas com Homeodomínio LIM/metabolismo , Células Ependimogliais/metabolismo , Hipotálamo/metabolismo , Hormônios Tireóideos/metabolismoRESUMO
Progesterone receptors (PRs) are biomarkers used as prognostic and predictive factors in breast cancer, but they are still not used as therapeutic targets. We have proposed that the ratio between PR isoforms A and B (PRA and PRB) predicts antiprogestin responsiveness. The MIPRA trial confirmed the benefit of 200 mg mifepristone, administered to patients with tumors with a high PRA/PRB ratio, but dose-ranging has not been conducted. The aim of this study was to establish the plasma mifepristone levels of patients from the MIPRA trial, along with the resultant steroid profiles, and compare these with those observed in mifepristone-treated mice using therapeutic schemes able to induce the regression of experimental mammary carcinomas with high PRA/PRB ratios: 6 mg pellets implanted subcutaneously, or daily doses of 12 mg/kg body weight. The plasma levels of mifepristone and other 19 plasma steroids were measured by liquid chromatography-tandem mass spectometry. In mifepristone-treated mice, plasma levels were lower than those registered in mifepristone-treated patients (i.e. day 7 after treatment initiation, pellet-treated mice: 8.4 ± 3.9 ng/mL; mifepristone-treated patients: 300.3 ± 31.7 ng/mL (mean ± s.d.; P < 0.001)). The increase in corticoid related steroids observed in patients was not observed in mifepristone-treated mice. The increase in progesterone levels was the most significant side effect detected in mifepristone-treated mice after 14 or 21 days of treatment, probably due to an ovarian compensatory effect not observed in postmenopausal patients. We conclude that in future clinical trials using mifepristone, the possibility of lowering the standard daily dose of 200 mg should be considered.
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Neoplasias da Mama , Mifepristona , Humanos , Camundongos , Animais , Feminino , Mifepristona/uso terapêutico , Mifepristona/farmacologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Receptores de Progesterona , Antagonistas de Hormônios/uso terapêutico , Antagonistas de Hormônios/farmacologia , PrognósticoRESUMO
The silver and blue fox appear closely related despite their belonging to different genera, and the male and female fox hybrids are completely sterile in mating inter se or back to either of the parental groups. In the present study, we compared ovarian morphology and serum hormone concentrations among silver foxes, blue foxes, HSBs (silver fox male × blue fox female hybrids) and HBSs (blue fox male × silver fox female hybrids) during the pre-breeding and the breeding period. We found that either the fertile blue and silver foxes or the infertile hybrid foxes showed typical characteristics of ovary, with primordial, primary, secondary, antral and Graafian follicles. The diameters and quantities of different follicle classes in fertile foxes were greater than that in hybrids during the two period, while the thickness of zona pellucida (ZP) represented an opposite trend (P < 0.05). The relative weight of bilateral ovaries in fertile foxes was greater than that in hybrids during the pre-breeding period, while mean serum FSH represented an opposite trend during the breeding period (P < 0.05). The mean serum estradiol in fertile foxes was greater than that in HBS foxes during the pre-breeding period, and greater than hybrids during the breeding period (P < 0.05). These findings indicated that in the infertile hybrid foxes, lower estradiol levels produced by lesser and smaller antral follicles, thicker ZP during the two period, higher FSH levels during the breeding period, could be the basis of interpretations in cases of female fox hybrid infertility.
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Infertilidade Feminina , Ovário , Feminino , Masculino , Animais , Raposas/anatomia & histologia , Reprodução , Infertilidade Feminina/veterinária , Estradiol , Hormônio FoliculoestimulanteRESUMO
Premature ovarian failure (POF) affects many adult women less than 40 years of age and leads to infertility. This study was aimed at exploring the improving effects of miR-22-3p on the symptoms of POF in mice by inhibiting chemokine-like receptor 1 (CMKLR1) expression. Female mice were intraperitoneally injected with cyclophosphamide to construct POF mice models. Lentiviral vectors containing miR-22-3p, short hairpin RNA (sh)-CMKLR1, and overexpression (oe)-CMKLR1, respectively, or in combination, were injected into the ovaries of both sides of POF mice. miR-22-3p and CMKLR1 expression in ovarian tissues of mice was assessed, and the targeting relationship between miR-22-3p and CMKLR1 was predicted and verified. Serum estradiol (E2), anti-Mullerian hormone, and follicle-stimulating hormone levels were assessed. Ovarian weight was weighed, and pathological changes and the number of primordial follicles, primary follicles, secondary follicles, and atresia follicles were observed. Apoptosis of ovarian tissues was determined. In ovarian tissues of POF mice, miR-22-3p expression was decreased while CMKLR1 expression was increased. miR-22-3p up-regulation or CMKLR1 down-regulation restored sex hormone levels, improved ovarian weight and the number of primordial follicles, primary follicles, and secondary follicles, and reduced the number of atresia follicle and ovarian granulosa cell apoptosis in POF mice. miR-22-3p targeted CMKLR1, and overexpressing CMKLR1 reversed the ameliorative effects of miR-22-3p overexpression on POF mice. Our research highlights that overexpressed miR-22-3p down-regulates CMKLR1 to ameliorate the symptoms of POF in mice. Therefore, the miR-22-3p/CMKLR1 axis could improve the symptoms of POF.
Assuntos
MicroRNAs , Insuficiência Ovariana Primária , Adulto , Feminino , Camundongos , Humanos , Animais , Insuficiência Ovariana Primária/patologia , Folículo Ovariano/metabolismo , Folículo Ovariano/patologia , Ciclofosfamida/farmacologia , MicroRNAs/metabolismo , Receptores de QuimiocinasRESUMO
The thyroid hormones play a pivotal role in various physiological processes, including growth, metabolism regulation, and reproduction. While non-modifiable factors are known to impact thyroid function, such as genetics and age, nutritional factors are also important. Diets rich in selenium and iodine are conventionally acknowledged to be beneficial for the production and release of thyroid hormones. Recent studies have suggested a potential link between beta-carotene, a precursor to vitamin A (retinol), and thyroid function. Beta-carotene is known for its antioxidant properties and has been shown to play a role in the prevention of various clinical conditions such as cancer and cardiovascular and neurological diseases. However, its impact on thyroid function is still unclear. Some studies have suggested a positive association between beta-carotene levels and thyroid function, while others have found no significant effect. Conversely, the hormone produced by the thyroid gland, thyroxine, enhances the conversion of beta-carotene to retinol. Furthermore, vitamin A derivatives are being explored as potential therapeutic options for thyroid malignancies. In this review, we highlight the mechanisms through which beta-carotene/retinol and thyroid hormones interact and review the findings of clinical studies examining the association between beta-carotene consumption and thyroid hormone levels. Our review underscores the need for further research to clarify the relationship between beta-carotene and thyroid function.
Assuntos
Fenômenos Fisiológicos , Glândula Tireoide , beta Caroteno , Vitamina A , Hormônios TireóideosRESUMO
This study was to investigate the association between sex hormone levels and metabolic syndrome (MetS) risk in female schizophrenia inpatients. In total, 93 female schizophrenia patients were enrolled based on their electronic medical records of hospitalization at the Zigong Psychiatric Research Center, China, between August 2022 to September 2022. Baseline information was collected retrospectively from medical records 6 months before. Logistic regression analysis was applied to assess the potential relationship between sex hormone levels and the risk of developing MetS. 31.2% (29/93) of the total patients, 25.5% (12/47) of the 18-49 age group, and 37.0% (17/46) of the ≥ 50 age group had a history of MetS; the newly-developed MetS prevalence among all female schizophrenia patients was 15.05% (14/93), which was slightly higher but not statistically significant in older patients (age ≥ 50) than in younger patients (age 18-49) (≥ 50 vs. 18-49, 21.74% vs. 8.5%, p = 0.074). Univariate analysis of sex hormone levels and developed MetS discovered that only high prolactin levels correlated with developed MetS in total participants (p = 0.006), especially in older patients (p = 0.004), while estradiol and testosterone levels were not associated. Furthermore, univariate logistic regression analysis of the total participants and with an adjusted model of the ≥ 50 age group confirmed the association of prolactin with MetS in all (OR = 1.016, 95%CI:1.002-1.029, p = 0.023), and older female schizophrenia patients (OR = 1.04, 95%CI: 1.01-1.07, p = 0.008). High serum levels of prolactin in older patients (age ≥ 50) were strongly correlated with the risk of developing MetS among female schizophrenia patients.