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Publication : Deletion of inositol polyphosphate 4-phosphatase type-II B affects spermatogenesis in mice.

First Author  Ceyhan Y Year  2020
Journal  PLoS One Volume  15
Issue  5 Pages  e0233163
PubMed ID  32413098 Mgi Jnum  J:343132
Mgi Id  MGI:6432928 Doi  10.1371/journal.pone.0233163
Citation  Ceyhan Y, et al. (2020) Deletion of inositol polyphosphate 4-phosphatase type-II B affects spermatogenesis in mice. PLoS One 15(5):e0233163
abstractText  Inositol polyphosphate-4-phosphatase type II (INPP4B) is a dual-specificity phosphatase that acts as a tumor suppressor in multiple cancers. INPP4B dephosphorylates phospholipids at the 4th position of the inositol ring and inhibits AKT and PKC signaling by hydrolyzing of PI(3,4)P2 and PI(4,5)P2, respectively. INPP4B protein phosphatase targets include phospho-tyrosines on Akt and phospho-serine and phospho-threonine on PTEN. INPP4B is highly expressed in testes, suggesting its role in testes development and physiology. The objective of this study was to determine whether Inpp4b deletion impacts testicular function in mice. In testis, Inpp4b expression was the highest in postmeiotic germ cells in both mice and men. The testes of Inpp4b knockout male mice were significantly smaller compared to the testes of wild-type (WT) males. Inpp4b-/- males produced fewer mature sperm cells compared to WT, and this difference increased with age and high fat diet (HFD). Reduction in early steroidogenic enzymes and luteinizing hormone (LH) receptor gene expression was detected, although androgen receptor (AR) protein level was similar in WT and Inpp4b-/- testes. Germ cell apoptosis was significantly increased in the knockout mice, while expression of meiotic marker gammaH2A.X was decreased. Our data demonstrate that INPP4B plays a role in maintenance of male germ cell differentiation and protects testis functions against deleterious effects of aging and high fat diet.
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