PTEN signaling through RAF1 proto-oncogene serine/threonine kinase (RAF1)/ERK in the epididymis is essential for male fertility

作者: Bingfang Xu , Angela M. Washington , Barry T. Hinton

DOI: 10.1073/PNAS.1413186112

关键词:

摘要: Without a fully developed initial segment, the most proximal region of epididymis, male infertility results. Therefore, it is important to understand development and regulation this crucial region. In addition distinctively high activity levels components ERK pathway, which are essential for initial-segment differentiation, segment exhibits protein phosphatase tensin homolog (PTEN). To role PTEN in we generated mouse model with conditional deletion Pten from epithelial cells epididymis postnatal day 17 (P17) onward. Shortly after deletion, hypertrophy became evident. Loss resulted activation AKT (protein kinase B) pathway P28 onward, turn gradually suppressed RAF1 proto-oncogene serine/threonine (RAF1)/ERK signaling through interaction between RAF1. Consistent progressive changes RAF1/ERK signaling, loss progressively altered cell shape, size, organization, proliferation, survival epithelium dedifferentiation extensive folding. Most importantly, knockout males lost fertility infertile 6 12 mo. Spermatozoa older mice showed lower percentage motility higher flagellar angulation compared controls, suggesting compromised sperm maturation. under normal physiological conditions, suppresses maintain maintains function therefore,

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