RESUMO
The homeodomain transcription factor SIX3 is a known regulator of eye, nose, and forebrain development, and has recently been implicated in female reproduction. Germline heterozygosity of SIX3 is sufficient to cause subfertility, but the cell populations that mediate this role are unknown. The neuropeptide kisspeptin is a critical component of the reproductive axis and plays roles in sexual maturation, ovulation, and the maintenance of gonadotropin secretion. We used Cre-Lox technology to remove Six3 specifically from kisspeptin neurons in mice to test the hypothesis that SIX3 in kisspeptin neurons is required for reproduction. We found that loss of Six3 in kisspeptin neurons causes subfertility and estrous cycle irregularities in females, but no effect in males. Overall, we find that SIX3 expression in kisspeptin neurons is an important contributor to female fertility.
Assuntos
Proteínas do Olho , Proteínas de Homeodomínio , Infertilidade , Kisspeptinas , Proteínas do Tecido Nervoso , Neurônios , Animais , Proteínas do Olho/genética , Proteínas do Olho/metabolismo , Feminino , Hormônio Liberador de Gonadotropina/metabolismo , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Kisspeptinas/genética , Kisspeptinas/metabolismo , Masculino , Camundongos , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Neurônios/metabolismo , Neuropeptídeos/metabolismo , Reprodução/fisiologia , Proteína Homeobox SIX3RESUMO
Regulation of Kiss1 transcription is crucial to the development and function of the reproductive axis. The homeodomain transcription factor, ventral anterior homeobox 1 (VAX1), has been implicated as a potential regulator of Kiss1 transcription. However, it is unknown whether VAX1 directly mediates transcription within kisspeptin neurons or works indirectly by acting upstream of kisspeptin neuron populations. This study tested the hypothesis that VAX1 within kisspeptin neurons regulates Kiss1 gene expression. We found that VAX1 acts as a repressor of Kiss1 in vitro and within the male arcuate nucleus in vivo. In female mice, we found that the loss of VAX1 caused a reduction in Kiss1 expression and Kiss1-containing neurons in the anteroventral periventricular nucleus at the time of the preovulatory luteinizing hormone surge, but was compensated by an increase in Kiss1-cFos colocalization. Despite changes in Kiss1 transcription, gonadotropin levels were unaffected and there were no impairments to fertility.
Assuntos
Núcleo Arqueado do Hipotálamo/metabolismo , Proteínas de Homeodomínio/genética , Hipotálamo Anterior/metabolismo , Kisspeptinas/genética , Neuropeptídeos/genética , Animais , Linhagem Celular , Feminino , Deleção de Genes , Regulação da Expressão Gênica , Gonadotropinas/metabolismo , Proteínas de Homeodomínio/metabolismo , Humanos , Kisspeptinas/metabolismo , Masculino , Camundongos , Camundongos Transgênicos , Neuropeptídeos/metabolismo , Regiões Promotoras Genéticas , Caracteres SexuaisRESUMO
OBJECTIVE: In 2002, the Chicago Department of Public Health (CDPH; Chicago, Illinois) convened the Chicago-Area Neonatal MRSA Working Group (CANMWG) to discuss and compare approaches aimed at control of methicillin-resistant Staphylococcus aureus (MRSA) in neonatal intensive care units (NICUs). To better understand these issues on a regional level, the CDPH and the Evanston Department of Health and Human Services (EDHHS; Evanston, Illinois) began an investigation. DESIGN: Survey to collect demographic, clinical, microbiologic, and epidemiologic data on individual cases and clusters of MRSA infection; an additional survey collected data on infection control practices. SETTING: Level III NICUs at Chicago-area hospitals. PARTICIPANTS: Neonates and healthcare workers associated with the level III NICUs. METHODS: From June 2001 through September 2002, the participating hospitals reported all clusters of MRSA infection in their respective level III NICUs to the CDPH and the EDHHS. RESULTS: Thirteen clusters of MRSA infection were detected in level III NICUs, and 149 MRSA-positive infants were reported. Infection control surveys showed that hospitals took different approaches for controlling MRSA colonization and infection in NICUs. CONCLUSION: The CANMWG developed recommendations for the prevention and control of MRSA colonization and infection in the NICU and agreed that recommendations should expand to include future data generated by further studies. Continuing partnerships between hospital infection control personnel and public health professionals will be crucial in honing appropriate guidelines for effective approaches to the management and control of MRSA colonization and infection in NICUs.
Assuntos
Controle de Infecções/organização & administração , Unidades de Terapia Intensiva Neonatal , Resistência a Meticilina , Infecções Estafilocócicas/epidemiologia , Chicago/epidemiologia , Infecção Hospitalar/prevenção & controle , Surtos de Doenças , Pesquisas sobre Atenção à Saúde , Humanos , Infecções Estafilocócicas/transmissão , Staphylococcus aureus/efeitos dos fármacosRESUMO
Hand hygiene is the best method of preventing transmission of infections in health care, but compliance is usually suboptimal. In one hospital, compliance with hand hygiene was improved and sustained using a multifaceted bundle approach. A unique aspect of the bundle was the creation of a violation letter that was sent to and enforced by managers of noncompliant personnel. The letter appeared to be the major factor in raising the hand hygiene compliance rate from 34% to >90% in a 2-year period.