Peroxisome Proliferator-activated Receptor-D (PPARD) Coordinates Mouse Spermatogenesis by Modulating Extracellular Signal-regulated Kinase (ERK)-dependent Signaling
| Autor: | Pei-Li Yao, Jeffrey M. Peters, Rex A. Hess, Li Ping Chen, Rolf Müller, Frank J. Gonzalez |
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| Rok vydání: | 2015 |
| Předmět: |
Male
MAPK/ERK pathway medicine.medical_specialty MAP Kinase Signaling System Receptors Cytoplasmic and Nuclear Peroxisome proliferator-activated receptor Biology Biochemistry Cell Line Mice Cyclin D1 Cyclin D2 Internal medicine medicine Animals Extracellular Signal-Regulated MAP Kinases Spermatogenesis Receptor Molecular Biology Cell Proliferation chemistry.chemical_classification Sertoli Cells Kinase Cell growth fungi food and beverages Cell Biology Sertoli cell Cell biology Endocrinology medicine.anatomical_structure chemistry Claudins Developmental Biology |
| Zdroj: | Journal of Biological Chemistry. 290:23416-23431 |
| ISSN: | 0021-9258 |
| Popis: | Ppard(-/-) mice exhibit smaller litter size compared with Ppard(+/+) mice. To determine whether peroxisome proliferator-activated receptor-D (PPARD) could possibly influence this phenotype, the role of PPARD in testicular biology was examined. Atrophic testes and testicular degeneration were observed in Ppard(-/-) mice compared with Ppard(+/+) mice, indicating that PPARD modulates spermatogenesis. Higher expression of p27 and decreased expression of proliferating cellular nuclear antigen in Sertoli cells were observed in Ppard(+/+) mice as compared with Ppard(-/-) mice, and these were associated with decreased Sertoli cell number in Ppard(+/+) mice. Cyclin D1 and cyclin D2 expression was lower in Ppard(+/+) as compared with Ppard(-/-) mice. Ligand activation of PPARD inhibited proliferation of a mouse Sertoli cell line, TM4, and an inverse agonist of PPARD (DG172) rescued this effect. Temporal inhibition of extracellular signal-regulated kinase (ERK) activation by PPARD in the testis was observed in Ppard(+/+) mice and was associated with decreased serum follicle-stimulating hormone and higher claudin-11 expression along the blood-testis barrier. PPARD-dependent ERK activation also altered expression of claudin-11, p27, cyclin D1, and cyclin D2 in TM4 cells, causing inhibition of cell proliferation, maturation, and formation of tight junctions in Sertoli cells, thus confirming a requirement for PPARD in accurate Sertoli cell function. Combined, these results reveal for the first time that PPARD regulates spermatogenesis by modulating the function of Sertoli cells during early testis development. |
| Databáze: | OpenAIRE |
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