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1.
Artigo em Inglês | MEDLINE | ID: mdl-37466351

RESUMO

INTRODUCTION: Health professions education often includes teaching observation to inform faculty development (FD) and indirectly improve student performance. Although these FD approaches are well received by faculty, they remain underused and/or underreported, with limited opportunities to receive feedback in workplace contexts. The goal of our study was to map the depth and breadth of education literature on the use of observation of teaching as a tool of professional development in medical education. METHODS: Following the methodology by Arksey and O'Malley, we conducted a scoping review and searched four databases for articles published in English (final searches in April 2022). RESULTS: Of 2080 articles identified, 45 met the inclusion criteria. All observation activities were associated with one of the following FD approaches: peer observation of teaching (23 articles, 51%), peer coaching (12, 27%), peer review (9, 20%), and the critical friends approach (1, 2%). Thirty-three articles (73%) concerned formative versions of the observation model that took place in clinical settings (21, 47%), and they tended to be a voluntary (27, 60%), one-off (18, 40%), in-person intervention (29, 65%), characterized by limited institutional support (13, 29%). Both barriers and challenges of teaching observation were identified. DISCUSSION: This review identified several challenges and shortcomings associated with teaching observation, such as inadequate methodological quality of research articles, inconsistent terminology, and limited understanding of the factors that promote long-term sustainability within FD programs. Practical strategies to consider when designing an FD program that incorporates teaching observation are outlined.

2.
Fam Med ; 53(5): 390, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-34019692
3.
Fam Med ; 53(1): 9-22, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33471918

RESUMO

BACKGROUND AND OBJECTIVES: The implementation of effective competency-based medical education (CBME) relies on building a coherent and integrated system of assessment across the continuum of training to practice. As such, the developmental progression of competencies must be assessed at all stages of the learning process, including continuing professional development (CPD). Yet, much of the recent discussion revolves mostly around residency programs. The purpose of this review is to synthesize the findings of studies spanning the last 2 decades that examined competency-based assessment methods used in family medicine residency and CPD, and to identify gaps in their current practices. METHODS: We adopted a modified form of narrative review and searched five online databases and the gray literature for articles published between 2000 and 2020. Data analysis involved mixed methods including quantitative frequency analysis and qualitative thematic analysis. RESULTS: Thirty-seven studies met inclusion criteria. Fourteen were formal evaluation studies that focused on the outcome and impact evaluation of assessment methods. Articles that focused on formative assessment were prevalent. The most common levels of educational outcomes were performance and competence. There were few studies on CBME assessment among practicing family physicians. Thematic analysis of the literature identified several challenges the family medicine educational community faces with CBME assessment. CONCLUSIONS: We recommend that those involved in health education systematically evaluate and publish their CBME activities, including assessment-related content and evaluations. The highlighted themes may offer insights into ways in which current CBME assessment practices might be improved to align with efforts to improve health care.


Assuntos
Educação Médica , Internato e Residência , Competência Clínica , Educação Baseada em Competências , Medicina de Família e Comunidade , Humanos , Aprendizagem , Publicações
4.
J Contin Educ Health Prof ; 40(3): 147-157, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32898116

RESUMO

INTRODUCTION: The authors sought to identify how physician specialty certification is defined in the North American literature. METHODS: A rigorous, established six-stage scoping review framework was used to identify the North American certification literature published between January 2006 and May 2016 relating to physician specialty certification. Data were abstracted using a charting form developed by the study team. Quantitative summary data and qualitative thematic analysis of the purpose of certification were derived from the extracted data. RESULTS: A two stage screening process identified 88 articles that met predefined criteria. Only 14 of the 88 articles (16%) contained a referenced purpose of certification. Eighteen definitions were identified from these articles. Definitional concepts included lifelong learning and continuous professional development, assessment of competence and performance, performance improvement, public accountability, and professional standing. DISCUSSION: Most articles identified in this scoping review did not define certification or describe its purpose or intent. Future studies should provide a definition of certification to further scholarly examination of its intent and effects and inform its further evolution.


Assuntos
Certificação/classificação , Médicos/tendências , Certificação/tendências , Humanos , América do Norte , Médicos/classificação
5.
Fam Med ; 52(4): 246-254, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32267519

RESUMO

BACKGROUND AND OBJECTIVES: While family medicine has been one of the first specialties to implement competency-based medical education (CBME) in residency, the nature and level of its integration with continuing professional development (CPD) is neither well understood nor well studied. The purpose of this review was to examine the current state of CBME implementation in family medicine residency and CPD programs in the North American education literature, with the aim of identifying implementation concepts and strategies that are generalizable to other medical settings to inform the design and implementation of residency training and CPD. METHODS: Using an Arksey and O'Malley six-step framework, we searched five online databases and the gray literature over the period between January 2000 through April 2017. We included full-text articles that focused on the key words CBME, residency, CPD, and family medicine. RESULTS: Of the articles reviewed, 37 met the inclusion criteria and were selected for full review. Eighty six percent of included articles focused on foundation elements related to designing competency-based curriculum and assessment strategies rather than program evaluation or other outcome measures. Only 19% of the articles were related to CPD that focused only on the implementation at the program and/or institution/organization levels. CONCLUSIONS: Given that the implementation of CBME is in its relative infancy, the pattern of implementation activities described in this scoping review reflected a limited focus on a broad range of issues related to fidelity of implementation of this complex intervention.


Assuntos
Internato e Residência , Canadá , Educação Baseada em Competências , Currículo , Medicina de Família e Comunidade , Humanos , Estados Unidos
6.
Acad Med ; 95(7): 1106-1119, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-31996559

RESUMO

PURPOSE: To examine the extent, range, and nature of how competency-based medical education (CBME) implementation terminology is used (i.e., the conceptualization of CBME-related terms) within the family medicine postgraduate medical education (PGME) and continuing professional development (CPD) literature. METHOD: This scoping review's methodology was based on Arksey and O'Malley's framework and subsequent recommendations by Tricco and colleagues. The authors searched 5 databases and the gray literature for U.S. and Canadian publications between January 2000 and April 2017. Full-text English-language articles on CBME implementation that focused exclusively on family medicine PGME and/or CPD programs were eligible for inclusion. A standardized data extraction form was used to collect article demographic data and coding concepts data. Data analysis used mixed methods, including quantitative frequency analysis and qualitative thematic analysis. RESULTS: Of 470 unique articles identified, 80 (17%) met the inclusion criteria and were selected for inclusion in the review. Only 12 (15%) of the 80 articles provided a referenced definition of the coding concepts (i.e., referred to an article/organization as the definition's source), resulting in 19 highly variable-and 12 unique- referenced definitions of key terms used in CBME implementation (competence, competency, competency-based medical education). Thematic analysis of the referenced definitions identified 15 dominant themes, among which the most common were (1) a multidimensional and dynamic concept that encompasses a variety of skill components and (2) being able to use communication, knowledge, technical skills, clinical reasoning, judgment, emotions, attitudes, personal values, and reflection in practice. CONCLUSIONS: The construction and dissemination of shared definitions is essential to CBME's successful implementation. The low number of referenced definitions and lack of consensus on such definitions suggest more attention needs to be paid to conceptual rigor. The authors recommend those involved in family medicine education work with colleagues across medical specialties to develop a common taxonomy.


Assuntos
Educação Baseada em Competências/métodos , Formação de Conceito/fisiologia , Educação Médica/métodos , Medicina de Família e Comunidade/educação , Canadá/epidemiologia , Competência Clínica/normas , Comunicação , Educação Médica Continuada/métodos , Emoções/fisiologia , Estudos de Avaliação como Assunto , Humanos , Julgamento/fisiologia , Conhecimento , Publicações/tendências , Teste de Apercepção Temática/estatística & dados numéricos , Estados Unidos/epidemiologia
7.
J Nurs Adm ; 49(1): 12-18, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30499867

RESUMO

OBJECTIVE: The aim of this study was to construct a sensitizing definition of certification in nursing for research purposes that can provide a foundation from which to further develop a coherent research program building evidence about the impact of certification on healthcare outcomes. BACKGROUND: The lack of a single definition of certification in nursing makes it difficult to draw conclusions about the relationship between specialty certification and patient outcomes. METHODS: This study was guided by the Delphi-Chaffee hybrid methodology proposed by Grant et al. DISCUSSION: Constructing a single, sensitizing definition of certification: 1) provides coherency for direction of certification research; 2) serves as a guide for researchers; and 3) facilitates multimethodological approaches to exploring the relationship among the different components of the definition of certification. CONCLUSION: A sensitizing definition of certification provides an opportunity for researchers to study the relationship between nursing certification and patient outcomes.


Assuntos
Certificação/métodos , Certificação/normas , Consenso , Pesquisa em Enfermagem , Especialidades de Enfermagem/normas , Técnica Delphi , Humanos
8.
MedEdPublish (2016) ; 8: 145, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-38440164

RESUMO

This article was migrated. The article was marked as recommended. There is a growing worldwide awareness in the field of health professions education and research that a successful implementation of competency-based medical education (CBME) requires embracing all stages of professional development (from undergraduate, through residency to continuing education). However, despite increased levels of cognizance and even enthusiasm about the importance of the entire continuum for the ultimate goal of improved healthcare, much work still remains as CBME principles are not widely adopted in continuing professional development (CPD). Much has been written about the process of competency-based curriculum development (e.g., the formation and development of meaningful and measurable outcomes) in undergraduate studies and postgraduate training, but not in CPD. If we expect a CPD curriculum to integrate CBME, competencies must be developed and clearly specified how they will fit into a coherent and implementable curriculum structure. In this article, we describe existing practices some educational institutions have, including our experiences in the Office of CPD at the University of Ottawa, Canada, in designing a competency-based curriculum and provide 12 tips for those who begin their journey of organizing, developing, and implementing such curricula. We conclude that in order to translate a competency-based approach into CPD, educational programs will have to refine curricula across health professionals' education using curriculum mapping as an important tool of curriculum development and evaluation.

9.
J Nurs Adm ; 48(5): 238-246, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29629910

RESUMO

OBJECTIVE: To identify how certification is defined, conceptualized, and discussed in the nursing literature. BACKGROUND: Although it is hypothesized that credentialing is associated with better patient outcomes, the evidence is relatively limited. Some authors have suggested that the lack of consistency used to define certification in nursing literature may be one of the dominant obstacles in credentialing research. METHODS: This scoping review was guided by Arksey and O'Malley's framework, and quantitative and qualitative analyses were conducted. RESULTS: The final data set contained a total of 36 articles, of which 14 articles provided a referenced definition of certification. Thematic analysis of the definitions yielded 8 dominant themes. CONCLUSION: The lack of a common definition of certification in nursing must be addressed to advance research into the relationship between certification processes in nursing and healthcare outcomes.


Assuntos
Certificação/normas , Educação em Enfermagem/normas , Licenciamento em Enfermagem/normas , Especialidades de Enfermagem/normas , Canadá , Competência Clínica , Humanos , Estados Unidos
12.
J Public Health Policy ; 31(1): 30-50, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20200524

RESUMO

The present study examines how growing socio-economic inequalities in transitional countries that have followed different health policy paths affect women's access to reproductive health care. I conducted surveys in Kazakhstan and Belarus and used logistic regression analyses to determine accessibility to and satisfaction with reproductive health services, reproductive status, and reproductive history based on country of residence. By all measures, access to reproductive health services was most problematic for the low-income women in Kazakhstan but to a significantly lesser extent for economically disadvantaged respondents in Belarus. Differences in education had a significant effect on women's access to reproductive health services in Kazakhstan but were not present in Belarus. Household income was the most powerful predictor of self-perceived health in Kazakhstan, but not in Belarus. The unreformed health-care system in Belarus appears to be more accessible for all women than Kazakhstan's health-care system that underwent significant market-oriented reform.


Assuntos
Disparidades em Assistência à Saúde , Serviços de Saúde Reprodutiva , Adolescente , Adulto , Estudos Transversais , Feminino , Acessibilidade aos Serviços de Saúde , Humanos , Cazaquistão , Modelos Logísticos , Pessoa de Meia-Idade , República de Belarus , Classe Social , Adulto Jovem
13.
Obesity (Silver Spring) ; 14(7): 1142-54, 2006 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-16899795

RESUMO

OBJECTIVE: To investigate the relationship of early obesity to metabolic syndrome during sex hormonal imbalances in mutant female mice at different ages. RESEARCH METHODS AND PROCEDURES: Hormonal imbalances, accumulation and nature of adipose tissue, food intake, glucose tolerance, and expression of candidate genes and markers of inflammation were studied by comparing wild-type, null, and haploinsufficient follitropin receptor knockout female mice at different ages. RESULTS: Follitropin receptor deletion in mice produced null females that are infertile and haploinsufficient mice that undergo accelerated biological aging. Both types of mutants with sex hormonal imbalances have central obesity without hyperphagia, but circulating leptin is elevated. Adipocyte hyperplasia and hypertrophy is attributed to elevated peroxisome proliferator-activated receptor gamma expression. Adiponectin protein levels increase in fat tissue and plasma. Only mutants but not controls acquire age-dependent decline in glucose tolerance with high insulin and altered pancreatic beta cells. Changes in inflammation markers, decreased muscle insulin receptor phosphorylation, and increase of the enzyme protein tyrosine phosphatase 1B indicate insulin resistance. DISCUSSION: In this animal model, the chronological appearance of early obesity induced by hormonal imbalances culminates in characteristics that are attributable to metabolic syndrome, including cardiovascular abnormalities. Dissection of the depot-specific alterations and defining molecular interrelationships could help in developing targeted remedies and resolving complications and controversies related to health benefits and adversities of current hormone replacement therapy.


Assuntos
Tecido Adiposo/metabolismo , Envelhecimento/genética , Regulação da Expressão Gênica , Hormônios Esteroides Gonadais/fisiologia , Síndrome Metabólica/genética , Obesidade/genética , PPAR gama/metabolismo , Adiponectina/sangue , Envelhecimento/fisiologia , Animais , Modelos Animais de Doenças , Feminino , Hormônio Foliculoestimulante/metabolismo , Teste de Tolerância a Glucose , Hormônios Esteroides Gonadais/genética , Hormônios Esteroides Gonadais/metabolismo , Inflamação , Resistência à Insulina , Peptídeos e Proteínas de Sinalização Intercelular , Leptina/sangue , Síndrome Metabólica/metabolismo , Camundongos , Camundongos Knockout , Obesidade/metabolismo , Receptores do FSH/genética
14.
Exp Gerontol ; 41(2): 117-22, 2006 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-16352410

RESUMO

Reproductive senescence occurs in all female mammals with resultant changes in numerous body functional systems and several important features may be species-specific. Those features that appear to parallel human menopause and aging include general similarity of hormone profiles across the menopausal transition, progression to cycle termination through irregular cycles, declining fertility with age, disturbances in thermogenesis, age-related gains in body weight, fat distribution and disposition towards metabolic syndrome. Structural and hormonal changes in the brain and ovary play a critical role in determining the onset of reproductive senescence. The short life span of rodents such as mice (compared to humans) and the ability to generate specific and timed gene deletions, provide powerful experimental paradigms to understand the molecular and functional changes that precede and follow the loss of reproductive capacity. In theory, any manipulation that compromises ovarian function either partly or totally would impact reproductive events at various levels followed by other dysfunctions. In this article, we provide an overview of three mouse models for the study of female reproductive aging. They are derived from different strategies and their age related phenotypes have been characterized to varying degrees. The follitropin receptor knockout (FORKO) mouse, in its null and haploinsufficient state as well as the dioxin/aryl hydrocarbon receptor (AhR) knockout mouse, serve as two examples of single gene deletions. A third model, using administration of a chemical toxicant such as 4-vinylcyclohexene diepoxide (VCD) in the adult state, produces ovarian deficiencies accompanied by aging changes. These will serve as useful alternatives to previously used radical ovariectomy in young adults. It is anticipated that these new models and more that will be forthcoming will extend opportunities to understand reproductive aging and resolve controversies that abound on issues related to benefits and risks of hormone replacement therapy or other modalities for improving quality of life.


Assuntos
Envelhecimento/fisiologia , Menopausa/fisiologia , Modelos Animais , Animais , Carcinógenos , Cicloexanos , Cicloexenos , Poluentes Ambientais , Feminino , Hormônios Esteroides Gonadais/fisiologia , Camundongos , Camundongos Knockout , Camundongos Mutantes , Ovário/efeitos dos fármacos , Compostos de Vinila
15.
Endocrine ; 26(3): 219-26, 2005 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-16034175

RESUMO

This review highlights observations gleaned from recent reports on the deletion of FSH and LH receptors in mice. Gonadal differentiation does not depend on the presence of gonadotropin receptors but development is affected to varying degrees in both sexes. In both knockouts the null females are infertile with severely underdeveloped gonads and accessory structures. Sexual maturity and/or pubertal delay occur depending on the sex and knockout. Male null FSH-R mice have reduced fertility but null LH-R males are sterile due to cryptorchid testes and deficient spermatogenesis. In null FSH-R females hormonal imbalances are due to deficient estrogen and hyperandrogenemia. LH-R deficient females have low estrogen and testosterone. Females in both knockouts display phenotypes such as obesity, bone deficiency, and changes in brain structure and function in addition to manifestation of different types of reproductive tract tumors. Both types of mice represent good models for testing hormone replacement therapy in different combinations. The FSH-R heterozygous females could also be useful for studying age-dependent phenotypes.


Assuntos
Marcação de Genes , Receptores do FSH/genética , Receptores do LH/genética , Reprodução/genética , Animais , Feminino , Fertilidade/genética , Engenharia Genética , Masculino , Camundongos , Camundongos Knockout , Modelos Animais , Fatores Sexuais , Transdução de Sinais/genética
16.
Exp Neurol ; 183(2): 559-72, 2003 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-14552897

RESUMO

Age-related neurodegenerative conditions are characterized by neuronal death and degeneration that lead to a progressive functional decline. Among the factors influencing degenerative processes during aging are altered levels of neurotrophic ovarian steroid 17beta-estradiol (E2). The follitropin receptor knockout (FORKO) female mouse displays hormonal imbalance characterized by very low levels of circulating E2 and high levels of testosterone. FORKO mice (24 days and 20 months) were used to investigate structural and functional changes in the central nervous system. We now show that the lifelong depletion of the sex hormone E2 in female FORKO mice correlates with abnormal behavior associated with defined alterations in brain morphology early in life, especially in aged animals. Immunohistochemical studies showed significant increases in the size and number of immunoreactive glial fibrillary acidic protein glial cells found in several brain regions (cortex and hippocampus) and a dramatic decline in estrogen receptors alpha and beta in the amygdala of FORKO females. These changes were associated with increased signs of anxiety in these animals. In the present study, we provide evidence that the chronic depletion of sex hormone E2 from early development leads to neural impairments in adult and aged FORKO mice that are associated with hypertrophy of glial cells, cell loss in distinct brain regions, and abnormal behavior. We suggest that the hormonal imbalance found in the female FORKO mouse provides an experimental paradigm for the study of morphological correlates of the behavioral changes that often accompany menopause in women.


Assuntos
Sistema Nervoso Central/patologia , Estrogênios/deficiência , Doenças Neurodegenerativas/genética , Doenças Neurodegenerativas/patologia , Receptores do FSH/deficiência , Fatores Etários , Tonsila do Cerebelo/metabolismo , Tonsila do Cerebelo/patologia , Animais , Ansiedade/genética , Aromatase/biossíntese , Comportamento Animal , Encéfalo/metabolismo , Encéfalo/patologia , Estradiol/deficiência , Receptor alfa de Estrogênio , Receptor beta de Estrogênio , Feminino , Proteína Glial Fibrilar Ácida/biossíntese , Homozigoto , Camundongos , Camundongos Knockout , Doenças Neurodegenerativas/fisiopatologia , Neuroglia/patologia , Neurônios/patologia , Receptores de Estrogênio/biossíntese , Receptores do FSH/genética , Útero/patologia
17.
Neuroreport ; 14(12): 1617-22, 2003 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-14502087

RESUMO

Progressive and long-term sex hormone imbalance in the FSH-R haploinsufficient menopausal mouse leads to degenerative changes in the CNS associated with increased anxiety. The brain region most affected by aging in these mice is the hippocampus. Choline acetyltransferase (ChAT) enzymatic activity and synapsin immunoreactivity are reduced at 20 months of age. Neurons in the dentate gyrus show signs of progressive degenerative changes, hypertrophy and glyosis, and subsequent cell shrinkage and death. These results suggest that the menopausal mouse mimics degenerative changes in the hippocampus of hormonally imbalanced aging humans. We propose using this animal model to test the effectiveness of potential therapeutics in paradigms of accelerated aging.


Assuntos
Envelhecimento , Sistema Nervoso Central/metabolismo , Hormônios Esteroides Gonadais , Menopausa , Modelos Animais , Receptores do FSH/deficiência , Envelhecimento/sangue , Envelhecimento/patologia , Envelhecimento/psicologia , Animais , Ansiedade/sangue , Ansiedade/patologia , Ansiedade/psicologia , Sistema Nervoso Central/patologia , Estradiol/sangue , Feminino , Hormônios Esteroides Gonadais/sangue , Menopausa/sangue , Menopausa/psicologia , Camundongos , Degeneração Neural/sangue , Degeneração Neural/metabolismo , Degeneração Neural/patologia , Receptores do FSH/genética , Testosterona/sangue
18.
Biol Reprod ; 69(4): 1281-93, 2003 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-12801993

RESUMO

Adult Follitropin Receptor Knockout (FORKO) female mice are infertile and estrogen deficient. In order to understand the peri/postnatal developmental changes, we have now characterized the structural and molecular aberrations by comparing several markers of follicular development in 2-, 10-, and 24-day-old wild-type and FORKO females. By Day 24, FORKO mice have 40%-50% smaller uteri and vaginas. Estradiol is undetectable but testosterone and LH levels are already elevated at this age. FORKO ovaries are 45% smaller, indicating a postnatal or perinatal deficit consequent to FSH receptor ablation. This is attributable to decreased numbers of growing follicles and reduced diameter. Developmental markers, such as Müllerian inhibiting substance, GATA-4, estrogen receptor beta, and androgen receptor, were differentially expressed in granulosa cells. In the 2-day-old mutant neonates, a faster recruitment process was noted that later slowed down, impeding development of follicles. This is noteworthy in light of the controversy regarding the direct role of FSH/receptor system as a determinant of small and preantral follicle development in rodents. As the pool of nongrowing primordial follicles specifies the duration of female fertility and timing of reproductive senescence, we believe that the postnatal FORKO female mouse could help in exploring the signals that impact on early folliculogenesis. In addition, our data suggest that the FSH/receptor system is a major contributor to the formation and recruitment of the nongrowing pool of follicles as early as Postnatal Day 2 in the mouse.


Assuntos
Folículo Ovariano/citologia , Ovário/crescimento & desenvolvimento , Ovário/metabolismo , Animais , Animais Recém-Nascidos , Hormônio Antimülleriano , Peso Corporal/genética , Ciclina D2 , Ciclinas/metabolismo , Proteínas de Ligação a DNA/metabolismo , Receptor beta de Estrogênio , Feminino , Fator de Transcrição GATA4 , Glicoproteínas/metabolismo , Hormônio Luteinizante/sangue , Masculino , Camundongos , Camundongos Knockout , Tamanho do Órgão , Folículo Ovariano/crescimento & desenvolvimento , Ovário/citologia , Receptores Androgênicos/metabolismo , Receptores de Estrogênio/metabolismo , Receptores do FSH/genética , Receptores do FSH/metabolismo , Hormônios Testiculares/metabolismo , Testosterona/sangue , Fatores de Transcrição/metabolismo , Útero/crescimento & desenvolvimento
19.
Biol Reprod ; 69(4): 1294-302, 2003 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-12801992

RESUMO

Targeted disruption of the mouse FSH receptor gene (FSH-R) that mediates the action of the FSH results in a gene dose-related ovarian phenotype in the developing as well as the adult animal. While null females (FORKO) are sterile, the haplo-insufficient mice experience early reproductive senescence. The purpose of this study was to first record changes in oocyte development in the null FORKO and haplo-insufficient mice. Oocyte growth is significantly retarded in the null mutants with thinner zona pellucida in preantral follicles, but thicker zona pellucida in secondary follicles. This morphometric change indicates developmental aberrations in coordination of the germ cell (oocyte) and the somatic granulosa cell (GC) compartments. Markers for primordial germ cell proliferation and oocyte growth, such as the c-Kit/Kit-ligand and bone morphogenetic protein-15 (BMP-15) were downregulated in both null and +/- ovaries, suggesting disrupted communication between oocyte and GCs. Extensive changes in the expression of other oocyte-specific gene products like the zona pellucida glycoproteins (zona pellucida A, B, and C) indicate major alteration in the extracellular matrix surrounding the germ cells. This led to leaky germ cells that allowed infiltration of somatic cells. These results show that the loss of FSH-R signaling alters the follicular environment, where oocyte-granulosa interactions are perturbed, creating an out-of-phase germ cell and somatic cell development. We believe that these data provide an experimental paradigm to explore the mechanisms responsible for preserving the structural integrity and quality of oocytes at different ages.


Assuntos
Oócitos/citologia , Oócitos/fisiologia , Oogênese/genética , Folículo Ovariano/crescimento & desenvolvimento , Receptores de Superfície Celular , Receptores do FSH/deficiência , Animais , Biomarcadores , Proteína Morfogenética Óssea 15 , Comunicação Celular , Proteínas do Ovo/metabolismo , Matriz Extracelular/fisiologia , Matriz Extracelular/ultraestrutura , Feminino , Fator 9 de Diferenciação de Crescimento , Heterozigoto , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Glicoproteínas de Membrana/metabolismo , Camundongos , Camundongos Mutantes , Folículo Ovariano/citologia , Folículo Ovariano/metabolismo , Proteínas Proto-Oncogênicas c-kit/metabolismo , Receptores do FSH/genética , Fator de Células-Tronco/metabolismo , Zona Pelúcida/metabolismo , Zona Pelúcida/fisiologia , Zona Pelúcida/ultraestrutura , Glicoproteínas da Zona Pelúcida
20.
Endocrinology ; 143(9): 3618-27, 2002 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-12193578

RESUMO

A fully functional FSH receptor (Fshr) is required for ovarian follicular development and fertility. Fshr null females are sterile because of failure of follicular maturation, ovulation, and estrogen deficiency. Because Fshr-haploinsufficient females also begin to show age-dependent reproductive deficits that mimic biological aging, we have investigated the changes that occur in the uterus of these mice. The uterine weight in 12-month-old Fshr +/- mice increased 2-fold, and most retired breeders (those that stopped breeding earlier than our wild-type females) developed unilateral uterine masses that appeared similar to several abnormalities that also occur in women and associated with infertility. Curiously, there was a tendency for most of the abnormality to occur in the right horn. Up to 25% of the virgin Fshr-haploinsufficient mice also developed pathology. These transformations were not present in either wild-type mice or the estrogen-deficient Fshr null females at any age. In haploinsufficient females, estrogen and progesterone were reduced and testosterone was elevated in circulation by 1 yr. Fshr-haploinsufficient mice developed an imbalance of progesterone receptor isoforms A and B in the uterus. This alteration of progesterone receptors along with an increase in LH receptors in the uterus may contribute to the induction of high frequency of uterine pathology. Angiogenesis, vascular abnormality, and adenomyosis appeared to be increased in the uterine horn bearing pathological mass. The Fshr-haploinsufficient mice might help in understanding the molecular basis of induction of uterine pathology and tissue patterning.


Assuntos
Envelhecimento , Heterozigoto , Receptores do FSH/deficiência , Receptores do FSH/genética , Útero/patologia , Animais , Endometriose/genética , Endometriose/patologia , Estradiol/sangue , Ciclo Estral , Feminino , Reabsorção do Feto/genética , Infertilidade Feminina/genética , Masculino , Camundongos , Camundongos Knockout , Neovascularização Patológica , Tamanho do Órgão , Gravidez , Progesterona/sangue , Receptores do LH/análise , Receptores do LH/metabolismo , Receptores de Progesterona/análise , Receptores de Progesterona/metabolismo , Testosterona/sangue , Útero/irrigação sanguínea , Útero/química
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