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Ovary |
INSERM U-407, Faculté de Médecine Lyon-Sud, 69921 Oullins, France
The present study was designed to establish the cellular localization and expression of transforming growth factor ß (TGFß) signaling pathway components, including TGFß1 and ß2; TGFß receptors type I (TßRI) and II (TßRII); and Smads 2, 3, 4, and 6 during gonadotropin-induced follicular maturation and ovulation in the mouse ovary. Immature 21-day-old mice were sequentially treated with recombinant human FSH, 5 IU daily for 3 days, and hCG once at Day 24 of life. Immunohistochemical experiments revealed a TGFß1 staining in granulosa cells (GC) and theca interna cells (TIC) as well as in oocytes, whereas that of TGFß2 was mainly localized in oocytes and GC. Strong immunostaining for both TßRI and -RII was observed in the TIC and, to a lesser extent, in GC. Whereas oocytes did not exhibit any staining for TßRII, their TßRI immunostaining was strong. Smads were detected in oocytes, GC, and luteal cells and in a lesser amount in TIC; the immunostaining for Smad 4 was the strongest. Western blotting and reverse transcription-polymerase chain reaction analyses indicated that, in response to gonadotropins, TGFß2, TßRI, Smad 2 and Smad 4 mRNA and protein levels increased, while those of Smad 6 decreased in ovarian homogenates. In conclusion, these results show that, in a model of immature mouse exposed to a sequential gonadotropin treatment, FSH and LH increased the expression of the TGFß signaling system through the increase of TGFß2, TßRI, stimulatory Smad 2, and common Smad 4 expression, which occurred concomitantly with a decrease of the inhibitory Smad 6 expression.
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