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In women, this typically entails irregular menstrual cycles, anovulation, or luteal phase defect

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However, it is not certain that the −8.8 kb Hdc enhancer is fully responsible for positive regulation of the Hdc gene, because in vivo importance of the +0.3 kb Hdc enhancer in Hdc gene transcription cannot be ruled out by the luciferase reporter gene transcription assay alone ( Despite remarkable progress in genome-wide annotation of potential enhancers, functional validation of annotated enhancers remains an unmet challenge