ABSTRACT
The role of fibroblast growth factor (FGF) 2 and FGF9 as mediators of cell-cell interactions between Sertoli cells (SCs) and peritubular cells (PCs) was investigated. Using RT-PCR, we demonstrated that SCs and PCs recovered from 20-day-old rats expressed several of the seven FGF receptors (FGFRs), and more specifically the FGFR1 IIIc. FGF2 and FGF9 did not elicit any morphological changes in primary cultures of SCs, nor did they alter the number of SCs in culture. By contrast, changes in shape were observed in FGF2- and FGF9-treated PCs. In addition, FGF2 but not FGF9 enhanced significantly and dose-dependently the number of PCs in culture, indicating that FGF2 was a survival factor for these cells. It was also mitogenic because it enhanced the [3H]thymidine labeling index in PCs. We next examined the effects of FGF2 and FGF9 in a coculture system using 20-day-old rat SCs and PCs, and in an organotypic culture system using XY rat embryonic gonads. In both models, FGF2 and FGF9 were found to promote cellular interactions as evidenced by the extent of cellular reorganization in the coculture system, and cord morphogenesis and growth in the organotypic culture system. A key feature in SC-PC interactions is the synthesis and remodeling of the basement membrane which is co-elaborated by the two cell types. Since basement membrane homeostasis depends upon the coordinated activity of proteinases and inhibitors, the proteinases and inhibitors produced by PCs and SCs degrading or opposing degradation of the major components of the basement membrane were further studied. Specifically, we monitored the metalloproteinases (MMP)-2 and -9 and the tissue inhibitors -1, -2 and -3, the plasminogen activators (PAs) and the PA inhibitor-1, using zymography for the proteinases and Western blots for the cognate inhibitors. Cocultures received FGF or an analog of cAMP in order to prevent cellular reorganization. We found that FGF2 was unique in inducing MMP-9 in coculture. Also, the enhanced levels of the PA inhibitor-1 and the 30 kDa band glycosylated form of tissue inhibitor-3 correlated with the enhanced SC-PC reorganization. It was concluded that FGF2 and FGF9 are morphogens for the formation of testicular cords.
Subject(s)
Epithelial Cells/cytology , Fibroblast Growth Factor 2/pharmacology , Fibroblast Growth Factor 9/pharmacology , Mesoderm/cytology , Testis/embryology , Animals , Cell Division/drug effects , Cell Shape/drug effects , Cells, Cultured , Coculture Techniques , DNA/biosynthesis , Epithelial Cells/drug effects , Male , Mesoderm/drug effects , Organ Culture Techniques , Rats , Reverse Transcriptase Polymerase Chain Reaction , Seminiferous Tubules/cytology , Seminiferous Tubules/drug effects , Sertoli Cells/cytology , Sertoli Cells/drug effects , Testis/drug effectsSubject(s)
Ovarian Follicle/growth & development , Ovary/growth & development , Aging , Animals , Female , Follicular Atresia , Rats , Sexual MaturationABSTRACT
Lhx9 (LIM/Homeobox gene 9) encodes a transcription factor implicated in various developmental processes, including gonadogenesis. Our observations in the rat show that Lhx9 expression present in undifferentiated gonads disappears as epithelial cells differentiate into Sertoli cells and begin to express AMH. In rat and in chick testes, Lhx9 expression present in interstitial cells decreases progressively to become undetectable after birth. In the female rat, Lhx9 is highly expressed in epithelial ovigerous cords of the fetal ovary. Its expression is down-regulated as epithelial cells differentiate into granulosa cells during the process of folliculogenesis occurring at birth. If this process is impaired by the lack of oocytes, ovigerous cord organization is maintained together with Lhx9 expression. In conclusion, Lhx9 expression can be inversely correlated with the commitment into a differentiation pathway of the different categories of mesothelium-derived cells of the gonad.
Subject(s)
Cell Differentiation/physiology , Homeodomain Proteins/genetics , Ovary/metabolism , Testis/metabolism , Amino Acid Sequence , Animals , Base Sequence , Chick Embryo , Epithelium/embryology , Epithelium/metabolism , Female , Gene Expression Profiling , Homeodomain Proteins/biosynthesis , Homeodomain Proteins/metabolism , LIM-Homeodomain Proteins , Male , Molecular Sequence Data , Ovary/embryology , Rats , Testis/embryology , Transcription FactorsABSTRACT
UNLABELLED: We report a rash after the first dose of antituberculosis polytherapy which raises questions concerning procedures to be followed. CASE REPORT: An 8-year-old child presented with a pruritic rash 1.5 hours after the first dose of isoniazide, rifampicine, pyrazinamide and ethambutol was simultaneously administered, which did not recur after successive re-administration of isoniazide and rifampicine. Pyrazinamide, which was re-administered last, induced a recurrence. Slower pyrazinamide re-administration allowed continuation of treatment. CONCLUSION: A protocol for re-administration of the four drugs is suggested.
