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
Understanding molecular structure and its influence on chemical reactivity is a fundamental component in Chemistry curriculum. For example, acidic protons ionize, or ionic solids dissociate to form charge, inducing electrolyte properties depending on molecular structure. An active learning lab is designed to demonstrate connection between electrolyte behavior and structure of various molecules. Experiments are shared to show interdisciplinary aspect of electrolytes within biology and chemistry. Specifically, how biomolecules exhibit electrolyte behavior due to chemical composition.