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Publication : Epididymal expression of the forkhead transcription factor Foxi1 is required for male fertility.

First Author  Blomqvist SR Year  2006
Journal  EMBO J Volume  25
Issue  17 Pages  4131-41
PubMed ID  16932748 Mgi Jnum  J:112876
Mgi Id  MGI:3663859 Doi  10.1038/sj.emboj.7601272
Citation  Blomqvist SR, et al. (2006) Epididymal expression of the forkhead transcription factor Foxi1 is required for male fertility. EMBO J 25(17):4131-41
abstractText  An essential aspect of male reproductive capacity is the immediate availability of fertilization-ready spermatozoa. To ensure this, most mammals rely on post-testicular sperm maturation. In epididymis, germ cells are matured and stored in a quiescent state that readily can be altered to produce active spermatozoa. This depends on active proton secretion into the epididymal lumen. We have identified Foxi1 as an important regulator of gene expression in narrow and clear cells-the major proton secretory cells of epididymal epithelia. Foxi1 appears to be required for the expression of the B1-subunit of the vacuolar H+ -ATPase proton pump and for carbonic anhydrase II as well as the chloride/bicarbonate transporter pendrin. Using transfection experiments, we have identified a Foxi1 binding cis-element in the ATP6V1B1 (encoding the B1-subunit) promoter that is critical for reporter gene activation. When this site is mutated to eliminate Foxi1 binding, activation is also abolished. As a consequence of defect Foxi1-dependent epididymal sperm maturation, we demonstrate that spermatozoa from Foxi1 null males fail to reach the female genital tract in sufficient number to allow fertilization.
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