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1.
Front Psychol ; 15: 1269016, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38741755

RESUMO

Cooperating with those around us is an important facet of functioning in modern-day society. Forming successful cooperative relationships requires trust, reciprocity, and other interpersonal skills that continue to develop during adolescence. This study examined the dynamic nature of how trust is formed and broken among 248 adolescents (Males = 110, M Age = 15.1 years) throughout an iterative cooperative task (i.e., the Trust Game) and the interindividual differences that alter the success of their relationships. In our study, adolescents from the same classroom were anonymously paired and played a 10-trial version of the Trust Game, which examines trust and reciprocity. We found that trust is formed in the first half of the game and decreases as the threat of defection nears in the last trial. As the game progressed, the relationship between trial number and investments on the subsequent trial was mediated by percent return (ab = -0.09, 95% CI = [-0.15, -0.02]). Importantly, this relationship was moderated by social skills (p = 0.003) and impulsivity (p = 0.001), such that increases in either were associated with decreased percent return and investments on future trials. Overall, we found that cooperation is an adaptive behavior which requires trust and reciprocity, and adolescents need to exhibit both of these behaviors to have fruitful interactions. These findings suggest that interventions to help students think about their partner's perspective and stress the longer-term nature of interactions with peers would foster successful cooperation in social situations.

2.
Biol Open ; 13(6)2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38712984

RESUMO

The mammary gland is a unique organ as most of its development occurs after birth through stages of proliferation, differentiation and apoptosis that are tightly regulated by circulating hormones and growth factors. Throughout development, hormonal cues induce the regulation of different pathways, ultimately leading to differential transcription and expression of genes involved in this process, but also in the activation or inhibition of post-transcriptional mechanisms of regulation. However, the role of microRNAs (miRNAs) in the different phases of mammary gland remodeling is still poorly understood. The objectives of this study were to analyze the expression of miRNA in key stages of mammary gland development in mice and to determine whether it could be associated with hormonal variation between stages. To do so, miRNAs were isolated from mouse mammary glands at stages of adulthood, pregnancy, lactation and involution, and sequenced. Results showed that 490, 473, 419, and 460 miRNAs are detected in adult, pregnant, lactating and involuting mice, respectively, most of them being common to all four groups, and 58 unique to one stage. Most genes could be divided into six clusters of expression, including two encompassing the highest number of miRNA (clusters 1 and 3) and showing opposite profiles of expression, reaching a peak at adulthood and valley at lactation, or showing the lowest expression at adulthood and peaking at lactation. GO and KEGG analyses suggest that the miRNAs differentially expressed between stages influence the expression of targets associated with mammary gland homeostasis and hormone regulation. To further understand the links between miRNA expression and hormones involved in mammary gland development, miRNAs were then sequenced in breast cells exposed to estradiol, progesterone, prolactin and oxytocin. Four, 38, 24 and 66 miRNAs were associated with progesterone, estradiol, prolactin, and oxytocin exposure, respectively. Finally, when looking at miRNAs modulated by the hormones, differentially expressed during mammary gland development, and having a pattern of expression that could be correlated with the relative levels of hormones known to be found in vivo, 16 miRNAs were identified as likely regulated by circulating hormones. Overall, our study brings a better understanding of the regulation of miRNAs throughout mammary gland development and suggests that there is a relationship between their expression and the main hormones involved in mammary gland development. Future studies will examine this role more in detail.


Assuntos
Lactação , Glândulas Mamárias Animais , MicroRNAs , MicroRNAs/genética , Animais , Feminino , Glândulas Mamárias Animais/metabolismo , Glândulas Mamárias Animais/crescimento & desenvolvimento , Camundongos , Gravidez , Perfilação da Expressão Gênica , Hormônios/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Regulação da Expressão Gênica , Biologia Computacional/métodos
3.
Br J Educ Psychol ; 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38537938

RESUMO

BACKGROUND: In the past decades, there has been a growing concern to understand why boys struggle in school. One of the turning points in students' educational trajectories likely to exacerbate boys' academic difficulties is students' enrolment in private or enriched school programmes, as boys are underrepresented in such programmes. METHOD: To better understand this gender imbalance, our research draws on a longitudinal design to examine whether grade 6 students' externalizing behaviours, school engagement and school grades in mathematics and language arts relate to secondary school programme attendance, among a sample size of 577 students (277 boys). RESULTS: Path analysis showed that only language arts grades predicted enrolment in private or selective public programmes and contributed to boys' underrepresentation in these programmes. CONCLUSIONS: Such findings have important implications for understanding boys' underachievement and low persistence in school as well as to guide interventions to promote gender and overall educational equity in school.

4.
Anxiety Stress Coping ; 37(1): 29-44, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37552634

RESUMO

BACKGROUND AND OBJECTIVES: Stress is not inherently negative. As youth will inevitably experience stress when facing the various challenges of adolescence, they can benefit from developing a stress-can-be-enhancing mindset rather than learning to fear their stress responses and avoid taking on challenges. We aimed to verify whether a rapid intervention improved stress mindsets and diminished perceived stress and anxiety sensitivity in adolescents. DESIGN AND METHODS: An online experimental design randomly exposed 233 Canadian youths aged 14-17 (83% female) to four videos of the Stress N' Go intervention (how to embrace stress) or to control condition videos (brain facts). Validated questionnaires assessing stress mindsets, perceived stress, and anxiety sensitivity were administered pre- and post-intervention, followed by open-ended questions. RESULTS: The intervention content successfully instilled a stress-can-be-enhancing mindset compared to the control condition. Although Bayes factor analyses showed no main differences in perceived stress or anxiety sensitivity between conditions, a thematic analysis revealed that the intervention helped participants to live better with their stress. CONCLUSIONS: Overall, these results suggest that our intervention can rapidly modify stress mindsets in youth. Future studies are needed to determine whether modifying stress mindsets is sufficient to alter anxiety sensitivity in certain adolescents and contexts.


Assuntos
Transtornos de Ansiedade , Ansiedade , Adolescente , Feminino , Humanos , Masculino , Ansiedade/terapia , Teorema de Bayes , Canadá
5.
Artigo em Inglês | MEDLINE | ID: mdl-37887691

RESUMO

Challenges faced by doctoral researchers led to a concerning "doctoral mental health crisis" within academia. Recognizing the pressing need to address mental health concerns, notably among doctoral students, the Quebec Ministry of Higher Education introduced the Higher Education Student Mental Health Action Plan 2021-2026. One potentially relevant intervention approach is the implementation of tailored structured writing retreats for graduate students. Aiming to measure and explain the effects of participating to a three-day writing retreat on doctoral mental health, this study followed an explanatory sequential mixed method, including an experimental design. One hundred doctoral researchers were randomly assigned to either the experimental group (n = 50) or the waitlist control trial group (n = 50). Both groups answered a questionnaire comprising validated scales and open-ended questions at different timepoints, separated by a two-week gap. Results reveal that writing retreats reduced doctoral researchers' psychological distress and improved their psychological, emotional, and social wellbeing. Among the multiple writing retreat aspects evaluated, only productivity experienced, as well as socialization/networking opportunities, acted as predictors for all doctoral mental health measures. Qualitative findings further supported the importance of perceived productivity and socialization/networking in promoting doctoral mental health. Recommendations are provided for fostering a supportive research work environment for doctoral researchers.


Assuntos
Saúde Mental , Redação , Humanos , Quebeque , Estudantes
6.
Sci Rep ; 12(1): 17599, 2022 10 20.
Artigo em Inglês | MEDLINE | ID: mdl-36266411

RESUMO

Western blotting experiments were initially performed to detect a target protein in a complex biological sample and more recently, to measure relative protein abundance. Chemiluminescence coupled with film-based detection was traditionally the gold standard for western blotting but accurate and reproducible quantification has been a major challenge from this methodology. The development of sensitive, camera-based detection technologies coupled with an updated technical approach permits the production of reproducible, quantitative data. Fluorescence reagent and detection solutions are the latest innovation in western blotting but there remains questions and debate concerning their relative sensitivity and dynamic range versus chemiluminescence. A methodology to optimize and produce excellent, quantitative western blot results with rigorous data analysis from membranes probed with both fluorescent and chemiluminescent antibodies is described. The data reveal when and how to apply these detection methods to achieve reproducible data with a stepwise approach to data processing for quantitative analysis.


Assuntos
Procedimentos Clínicos , Proteínas , Western Blotting , Proteínas/análise , Anticorpos , Confiabilidade dos Dados
7.
Toxicol Sci ; 189(2): 268-286, 2022 09 24.
Artigo em Inglês | MEDLINE | ID: mdl-35861430

RESUMO

Due to their endocrine disruption properties, phthalate plasticizers such as di(2-ethylhexyl) phthalate (DEHP) can affect the hormone-dependent development of the mammary gland. Over the past few years, DEHP has been partially replaced by 1,2-cyclohexane dicarboxylic acid diisononyl ester (DINCH) which also have potential endocrine disrupting properties. The goal of the present study is to understand the impact of a gestational and lactational exposure to DEHP and DINCH on mammary gland development using Sprague Dawley rats. Both plasticizers altered the adipocytes of the mammary gland fat pad of adult progeny, as demonstrated by a decrease in their size, folding of their membrane, and modulations of the lipid profiles. DEHP treatments decreased the expression of Rxrα and Scd1 at the low and high dose, respectively, but did not affect any of the other genes studied. DINCH modulation of lipid metabolism could be observed at puberty by a decreased expression of genes implicated in triglyceride synthesis, lipid transport, and lipolysis, but by an increased expression of genes of the ß-oxidation pathway and of genes involved in lipid storage and fatty acid synthesis at adulthood, compared with control and DEHP-treated rats. A strong upregulation of different inflammatory markers was observed following DINCH exposure only. Together, our results indicate that a gestational and lactational exposure to DINCH has earlier and more significant effects on lipid homeostasis, adipogenesis, and the inflammatory state of the adult mammary gland than DEHP exposure. The long-term consequence of these effects on mammary gland health remained to be determined.


Assuntos
Dietilexilftalato , Plastificantes , Animais , Cicloexanos , Ácidos Dicarboxílicos/toxicidade , Dietilexilftalato/toxicidade , Ésteres/toxicidade , Ácidos Graxos , Hormônios , Metabolismo dos Lipídeos , Lipídeos , Ácidos Ftálicos , Plastificantes/toxicidade , Ratos , Ratos Sprague-Dawley , Maturidade Sexual , Triglicerídeos
8.
Toxicol Sci ; 186(2): 190-207, 2022 03 28.
Artigo em Inglês | MEDLINE | ID: mdl-35104882

RESUMO

Brominated flame retardants (BFR) are molecules added to consumer products to reduce fire hazards. They were banned in North America and Europe because of their persistence and biomagnification. However, BFR are still released in the environment due to continued use of products manufactured before restriction, and from waste and recycling processes of those products. As a result, they remain sources of chronic environmental and human exposure worldwide. BFR are well-characterized endocrine disruptors. They have been associated with a wide range of alterations in endocrine and reproductive systems both in humans and experimental models in vivo and in vitro. Paradoxically, the effects of BFR on mammary glands, whose development and carcinogenesis are mainly under hormonal dependency are poorly known. There is increasing weight of evidence that exposure to endocrine disruptors promotes breast cancer, especially if the exposure occurs during sensitivity windows. For the mammary gland, these windows include the perinatal life, puberty, and pregnancy, as important remodeling of the organ happens during those periods. The peak of exposure to BFRs happened during late 1990s and beginning of 2000s in most countries. Women who were pregnant at that time are reaching menopause while their daughters are 20-30 years old. It is thus important to better understand the effects of BFRs on mammary gland development and breast cancer to determine whether these women are more at risk. Thus, this review aims to propose a comprehensive review of data reporting the effects of exposure to BFR on female endocrine and reproductive systems, with a particular focus on mammary gland development and of a potential increased risk of breast cancer.


Assuntos
Neoplasias da Mama , Disruptores Endócrinos , Retardadores de Chama , Hidrocarbonetos Bromados , Glândulas Mamárias Humanas , Adulto , Disruptores Endócrinos/toxicidade , Exposição Ambiental/efeitos adversos , Feminino , Retardadores de Chama/toxicidade , Éteres Difenil Halogenados , Humanos , Gravidez , Adulto Jovem
9.
Br J Educ Psychol ; 92(3): 1068-1085, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35170029

RESUMO

BACKGROUND: When exposed to evaluative situations, up to 40% of students develop test anxiety, reflected, namely, by extensive worry, intrusive thoughts, and physiological arousal. Though the negative influence of test anxiety on later school performance is well documented, the role of students' initial achievement in the development of later test anxiety is less clear. AIMS AND SAMPLE: To better capture the nature of the relations between prior mathematics and language arts achievement and later test anxiety across genders, this study examined linear and curvilinear relationships among 1,569 French-speaking Canadian students followed across the transition to secondary school, a critical period for test anxiety. METHODS: Students completed a questionnaire at the beginning and the end of the first year of secondary school, and schools provided us with students grades at the end of 6th grade and the fall of 7th grade. RESULTS: Multilevel regression analyses showed that only mathematics achievement at the end of elementary school predicted test anxiety at the beginning of secondary school. In secondary school, beginning-of-year achievement in both mathematics and language arts predicted test anxiety at the end of this same year, but different patterns were observed for boys and girls. CONCLUSIONS: Because nonlinear relations were observed at each timepoint, low achievers may not be the only group of students who are at greater risk of developing high levels of test anxiety. Therefore, interventions targeting students with different achievement profiles might help to reduce test anxiety and facilitate the transition to secondary school.


Assuntos
Instituições Acadêmicas , Ansiedade aos Exames , Logro , Ansiedade , Canadá , Feminino , Humanos , Masculino , Matemática
10.
Environ Res ; 205: 112435, 2022 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-34843719

RESUMO

Pregnancy is a complex process requiring tremendous physiological changes in the mother in order to fulfill the needs of the growing fetus, and to give birth, expel the placenta and nurse the newborn. These physiological modifications are accompanied with psychological changes, as well as with variations in habits and behaviors. As a result, this period of life is considered as a sensitive window as impaired functional and physiological changes in the mother can have short- and long-term impacts on her health. In addition, dysregulation of the placenta and of mechanisms governing placentation have been linked to chronic diseases later-on in life for the fetus, in a concept known as the Developmental Origin of Health and Diseases (DOHaD). This concept stipulates that any change in the environment during the pre-conception and perinatal (in utero life and neonatal) period to puberty, can be "imprinted" in the organism, thereby impacting the health and risk of chronic diseases later in life. Pregnancy is a succession of events that is regulated, in large part, by hormones and growth factors. Therefore, small changes in hormonal balance can have important effects on both the mother and the developing fetus. An increasing number of studies demonstrate that exposure to endocrine disrupting compounds (EDCs) affect both the mother and the fetus giving rise to growing concerns surrounding these exposures. This review will give an overview of changes that happen during pregnancy with respect to the mother, the placenta, and the fetus, and of the current literature regarding the effects of EDCs during this specific sensitive window of exposure.


Assuntos
Mães , Maturidade Sexual , Feminino , Feto , Humanos , Recém-Nascido , Placenta/metabolismo , Placentação , Gravidez
11.
Front Psychol ; 13: 1035494, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36619097

RESUMO

Background: Studies report a growing tendency for students to experience state anxiety in schools. However, the combination of individual susceptibilities likely to trigger students' anxious states remains unclear. Aims: This study examined whether distinct profiles of students emerge regarding their susceptibility to anxiety sensitivity and/or test anxiety and evaluated whether students' profile predicted anxious states. We also verified whether susceptibility profiles varied across gender, school level, and school type. Sample and methods: In total, 1,404 Canadian students in Grades 5 and 10 (589 boys; M age = 15.2, SD = 2.1) from 13 public and private schools completed self-reported measures of state/trait anxiety, anxiety sensitivity, and test anxiety. Results: Latent profile analyses identified four susceptibility profiles: (1) Double-susceptibility: highest anxiety sensitivity and test anxiety scores; (2) Unique-susceptibility to test anxiety: high test anxiety score and low anxiety sensitivity score; (3) Unique-susceptibility to anxiety sensitivity: high anxiety sensitivity score and low test anxiety score; and (4) No-susceptibility: lowest anxiety sensitivity and test anxiety scores. The profiles comprised 12, 9, 6, and 73% of the sample, respectively, and their membership varied across gender and school type, but not across school levels. A linear mixed-effect model showed that state anxiety varied significantly between profiles, where the Double-susceptibility profile predicted the highest state anxiety scores, followed by the two Unique-susceptibility profiles (indifferently), and the No-susceptibility profile. Conclusion: Beyond their theoretical contribution to the state-trait anxiety literature, these findings suggest that selective interventions designed more specifically for students with the Double-susceptibility profile may be worthwhile. Results also highlight the high proportion of students with the No-susceptibility profile and shed light on the reassuring portrait regarding students' anxiety.

12.
Sleep Disord ; 2021: 5546484, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33996158

RESUMO

This study is aimed at assessing the psychometric properties and the factorial structure of the Pittsburgh Sleep Quality Index (PSQI) in a clinical sample of children, adolescents, and young adults with chronic pain. Data of 482 participants (aged 8-21 years) from two crosssectional studies and a chronic pain services outpatient clinic were analyzed. Exploratory and confirmatory factor analysis and reliability analysis of PSQI component scores were performed. Relationships between the PSQI global score and various clinical measures were investigated to assess external validity. The findings exhibit the reliability and validity of a single-factor model of the PSQI in a clinical sample of youth with chronic pain and support the relationship in this specific population between poor sleep quality and important clinical measures of well-being. These results support an informed decision regarding its use with this specific population and underscore the clinical relevance of assessing sleep quality.

13.
Methods Cell Biol ; 163: 21-44, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33785167

RESUMO

Every year, over 2 million women are diagnosed with breast cancer. Although considerable progress was made within the last years in cancer prevention, diagnosis and treatment, breast cancer is still responsible for over 600,000 of deaths per year. Over the years, numerous mouse models have been developed to understand breast cancer etiology and progression. Among those, mammary carcinomas induced by carcinogen, such as 7,12-dimethylbenz[a]anthracene (DMBA), has been widely used. Generally, 30-70% of mice exposed to 4-6 weekly doses of 1mg of DMBA during the peripubertal period (4-10 weeks of age) will develop mammary tumors within 150-200 days after the first exposure, that sometime metastasize to the lungs. As a result, DMBA-induced tumorigenesis is thought to be an accurate and relevant model to study breast cancer as it closely mimics this multistep process. This chapter presents the typical protocol used in mice to induce mammary gland tumors using DMBA. The influence of the number of doses and the total burden of DMBA given, as well as of the age and strain of the mice on mammary gland incident and on tumor onset are discussed. The current knowledge regarding mechanisms involved in DMBA-induced tumorigenesis is also presented.


Assuntos
9,10-Dimetil-1,2-benzantraceno , Neoplasias Mamárias Experimentais , 9,10-Dimetil-1,2-benzantraceno/toxicidade , Animais , Antracenos , Carcinogênese , Carcinógenos/toxicidade , Neoplasias Mamárias Experimentais/induzido quimicamente , Camundongos
14.
Toxicol Sci ; 179(2): 206-219, 2021 01 28.
Artigo em Inglês | MEDLINE | ID: mdl-33252648

RESUMO

In utero and prepubertal development of the mammary glands occurs minimally in a hormone independent manner until puberty where maturation of the hypothalamic-pituitary-gonadal axis drives an extensive remodeling. Nevertheless, because the immature glands contain functional hormone receptors, they are especially vulnerable to the effects of endocrine disruptors, such as brominated flame retardants (BFRs). BFRs are widespread chemicals added to household objects to reduce their flammability, and to which humans are ubiquitously exposed. We previously reported that in utero and lactational exposure to BFRs resulted in an impaired mammary gland development in peripubertal animals. Here, we assessed whether BFR-induced disruption of mammary gland development could manifest earlier in life. Dams were exposed prior to mating until pups' weaning to a BFR mixture (0, 0.06, 20, or 60 mg/kg/day) formulated according to levels found in house dust. The mammary glands of female offspring were collected at weaning. Histo-morphological analyses showed that exposure to 0.06 mg/kg/day accelerates global epithelial development as demonstrated by a significant increase in total epithelial surface area, associated with a tendency to increase of the ductal area and thickness, and of lumen area. Significant increases of the Ki67 cell proliferation index and of the early apoptotic marker cleaved caspase-9 were also observed, as well as an upward trend in the number of thyroid hormone receptor α1 positive cells. These molecular, histologic, and morphometric changes are suggestive of accelerated pubertal development. Thus, our results suggest that exposure to an environmentally relevant mixture of BFRs induces precocious development of the mammary gland.


Assuntos
Disruptores Endócrinos , Retardadores de Chama , Hidrocarbonetos Bromados , Animais , Disruptores Endócrinos/toxicidade , Feminino , Retardadores de Chama/toxicidade , Humanos , Lactação , Ratos , Ratos Sprague-Dawley , Reprodução
15.
Front Psychol ; 12: 796073, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35185694

RESUMO

Despite progress, gender gaps persist in mathematical and language-related fields, and gender stereotypes likely play a role. The current study examines the relations between parents' gender-related beliefs and their adolescent child's motivation and career aspirations through a survey of 172 parent-child dyads. Parents reported their gendered beliefs about ability in mathematics and language arts, as well as their prescriptive gender role beliefs. Students reported their expectancies and values in these two domains, as well as their career aspirations The results of path models suggested that parents' ability stereotypes about language boosted girls' motivation for language arts, thereby nudging them away from STEM pathways. Girls' career aspirations stemmed not only from their valuation of the corresponding domain, but also from their valuation of competing domains. Such findings highlight the need to consider multiple domains simultaneously in order to better capture the complexity of girls' career decisions. For boys, parents' language ability stereotypes were directly related to mathematical career aspirations. These results suggest that stereotypes that language arts is not for boys push them instead toward mathematics. Our study also highlighted the unique role of parental beliefs in traditional gender roles for boys' motivation and career aspirations. Specifically, parents' gender role stereotypes directly related to less interest in language arts only among boys. This highlights that research into gender gaps in female-dominated fields should consider stereotypes related to appropriate behavior and social roles for boys.

16.
Phys Occup Ther Pediatr ; 40(5): 546-556, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32028813

RESUMO

AIMS: Spinal fusion surgery is one of the most invasive orthopedic surgeries. Pain while moving or a fear of experiencing pain after surgery may delay return to function and cause prolonged disability. The purpose of the study was to examine the psychometric properties of the Tampa Scale of Kinesiophobia (TSK) in pediatric patients undergoing scoliosis surgery. METHODS: Fifty-five adolescents (10-18 years old) scheduled for spinal fusion surgery were enrolled. Participants completed the TSK questionnaire before surgery and six weeks after surgery. Reliability, exploratory and confirmatory factor analyses were performed on the two-factors TSK including activity avoidance (TSK-AA) and somatic focus (TSK-SF). RESULTS: Before and after surgery, all TSK-AA items conformed into the same factor component and revealed good internal reliability with Cronbach's alpha of .76 and .70 respectively. TSK-SF items were separated into different factor components and revealed poor reliability (.11 and .56). The TSK-AA also produced an adequate fit to the data, as reflected with several fit indices at both timepoints, respectively: χ2/df = 1.19 and 1.22; CFI=.96 and .94; and RMSEA=.06 and .06. CONCLUSIONS: The TSK-AA demonstrated good psychometric properties in patients undergoing scoliosis surgery, which provides empirical evidence for pediatrics. Its validation in distinct populations and settings is recommended prior to its use.


Assuntos
Medo/psicologia , Transtornos Fóbicos/psicologia , Escoliose/psicologia , Escoliose/cirurgia , Fusão Vertebral/psicologia , Inquéritos e Questionários/normas , Adolescente , Criança , Feminino , Humanos , Masculino , Medição da Dor , Psicometria , Reprodutibilidade dos Testes
17.
Toxicol Sci ; 171(1): 13-31, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31241157

RESUMO

Mammary gland development requires hormonal regulation during puberty, pregnancy, and lactation. Brominated flame retardants (BFRs) are endocrine disruptors; they are added to consumer products to satisfy flammability standards. Previously, we showed that gestational and lactational exposure to an environmentally relevant mixture of BFRs disrupts proteins of the adherens junctions in rat dam mammary glands at weaning. Here, we hypothesize that perinatal exposure to the same BFR mixture also disrupts junctional proteins and signaling pathways controlling mammary gland development in pups. Dams were exposed through diet to a BFR mixture based on the substances in house dust; doses of the mixture used were 0, 0.06, 20, or 60 mg/kg/day. Dams were exposed continuously beginning prior to mating until pups' weaning; female offspring were euthanized on postnatal day (PND) 21, 46, and 208. The lowest dose of BFRs significantly downregulated adherens junction proteins, E-cadherin, and ß-catenin, and the gap junction protein p-Cx43, as well as thyroid hormone receptor alpha 1 protein at PND 46. No effects were observed on estrogen or progesterone receptors. The low dose also resulted in a decrease in cleaved caspase-3, a downward trend in PARP levels, proteins involved in apoptosis, and an upward trend in proliferating cell nuclear antigen, a marker of proliferation. No effects were observed on ductal elongation or on the numbers of terminal end buds. Together, our results indicate that gestational and lactational exposure to an environmentally relevant mixture of BFRs disrupts cell-cell interactions, thyroid hormone homeostasis and the proliferation-apoptosis balance at PND 46, a critical stage for mammary gland development.

18.
Environ Res ; 173: 165-173, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30909102

RESUMO

The di(2-ethylhexyl) phthalate (DEHP) is a plasticizer incorporated to plastic matrices of widely used consumer products. However, it is gradually released from these products, resulting in a chronic exposure for humans. Although DEHP, similar to other members of the phthalates family, is generally considered as an endocrine disruptor, the mechanisms implicated in its toxicity are yet poorly understood. Our objective was to determine the effects of an exposure to DEHP and to one of its major metabolite, the mono(2-ethylhexyl) phthalate (MEHP) on markers involved in breast carcinogenesis. T-47D cells were exposed to environmentally relevant and higher doses of DEHP and MEHP (0.1-10 000 nM) for 4 days. Our results showed that an exposure to 10 000 nM of DEHP and 0.1 nM of MEHP significantly increased the proliferation of T-47D cells, without inducing apoptosis. In addition, a significant increase in the protein levels of the isoform A of the progesterone receptor (PR) and of nuclear levels of PR were observed in T-47D cells exposed to 10 000 nM of DEHP. Importantly, the increased proliferation and nuclear levels of PR were totally and partially inhibited, respectively, by Mifepristone, a PR antagonist. These results suggest that an exposure to DEHP or MEHP increase cell proliferation by activating PR signaling, which could potentially increase the risks to develop breast cancer. The mechanism of activation of the progesterone pathway by DEHP and the long-term consequences of this activation remained to be elucidated.


Assuntos
Neoplasias da Mama , Dietilexilftalato/toxicidade , Receptores de Progesterona/metabolismo , Proliferação de Células , Humanos , Ácidos Ftálicos
19.
Future Sci OA ; 4(7): FSO315, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30112185

RESUMO

The epithelium's functional unit is the bilayered acinus, made of a layer of luminal cells, surrounded by a layer of basal cells mainly composed of myoepithelial cells. AIM: The aim of this study was to develop a reproducible and manipulable 3D co-culture model of the bilayered acinus in vitro to study the interactions between the two layers. MATERIALS & METHODS: Two different combinations of cell lines were co-cultured in Matrigel: SCp2 and SCg6 mice cells, or MCF-12A and Hs 578Bst human cell lines. RESULTS: Confocal microscopy analysis showed that only MCF-12A and Hs 578Bst cells could form some bilayered acini. This in vitro bilayered acini model will allow us to understand the role of interactions between luminal and myoepithelial cells in the normal breast development.

20.
Int J Mol Sci ; 19(3)2018 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-29495625

RESUMO

Gap junction transmembrane channels allow the transfer of small molecules between the cytoplasm of adjacent cells. They are formed by proteins named connexins (Cxs) that have long been considered as a tumor suppressor. This widespread view has been challenged by recent studies suggesting that the role of Connexin 43 (Cx43) in cancer is tissue- and stage-specific and can even promote tumor progression. High throughput profiling of invasive breast cancer has allowed for the construction of subtyping schemes that partition patients into at least four distinct intrinsic subtypes. This study characterizes Cx43 expression during cancer progression with each of the tumor subtypes using a compendium of publicly available gene expression data. In particular, we show that Cx43 expression depends greatly on intrinsic subtype. Tumor grade also co-varies with patient subtype, resulting in Cx43 co-expression with grade in a subtype-dependent manner. Better survival was associated with a high expression of Cx43 in unstratified and luminal tumors but with a low expression in Her2e subtype. A better understanding of Cx43 regulation in a subtype-dependent manner is needed to clarify the context in which Cx43 is associated with tumor suppression or cancer progression.


Assuntos
Neoplasias da Mama/metabolismo , Conexina 43/metabolismo , Animais , Biomarcadores , Neoplasias da Mama/genética , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Conexina 43/genética , Feminino , Junções Comunicantes/metabolismo , Expressão Gênica , Humanos , Imuno-Histoquímica , Prognóstico , Transporte Proteico , Receptores de Estrogênio/genética , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/genética , Receptores de Progesterona/metabolismo
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