Follicle Atresia Is Regulated by Fibroblast Growth Factor-18 in Cattle.
Notice bibliographique
Résumé
Understanding the paracrine events that regulate fertility in the cow is necessary not only because of the agricultural importance of this species, but also its potential use as a model for humans. Fibroblast growth factors (FGF) and their receptors are involved in the paracrine modulation of ovarian function. For example, FGF2, 7 and 10 inhibit estradiol secretion by granulosa cells in vitro. Another member of this family, FGF8, is an oocyte-derived protein that modulates glycolysis in cumulus cells. FGFs are grouped into subfamilies of closely-related proteins, and FGF18 is in the same subfamily as FGF8 and has also been detected in mouse oocytes. The existance of a subfamily of FGFs that are specifically derived from the oocyte are potentially interesting paracrine regulators of fertility. The objectives of the present study were to localize the expression of FGF18 in the bovine follicle, to gain insight into the control of FGF18 expression and to identify potential actions of FGF18 in the follicle. Bovine ovaries were obtained from an abattoir for localizing expression patterns by real-time PCR and immunohistochemistry. FGF18 mRNA was not detected in pooled oocytes by PCR, but was present in isolated theca and granulosa cells (GC), and protein was detected in the follicle wall by immunohistochemistry. Expression during follicle growth was measured by collecting the two largest follicles per cow at defined stages of the first follicle wave. The follicles were classified as dominant and subordinate according to estradiol levels in follicular fluid and aromatase mRNA abundance in GC. FGF18 mRNA abundance in both GC and theca cells was higher in subordinate follicles compared with dominant follicles (P<0.05). To determine regulation and function of FGF18, granulosa cells were isolated from 5-8 mm follicles and employed in an estrogenic, serum-free culture system. In vitro, FGF18 expression was down-regulated by IGF1, insulin, FGF2, FGF10 (P<0.05) in GC. In further experiments, the addition of graded doses of FGF18 (0, 1, 10, 100 ng/ml) to GC in culture inhibited estradiol secretion and abundance of mRNA encoding the estrogenic enzymes aromatase and 17β-hydroxysteroid dehydrogenase (17βHSD), and the FSH receptor. Progesterone secretion was also inhibited, which was associated with decreased abundance of mRNA encoding CYP11, StAR and 3βHSD. Assessment of apoptosis by flow cytometry showed that FGF18 significantly increased the proportion of apoptotic cells, and this was accompanied by decreased abundance of mRNA encoding antiapoptotic and proliferation genes (MIF, RFC4 and GADD45B). In summary, FGF18 is expressed in GC and theca cells but--in contrast to the subfamily prototype, FGF8--not in oocytes in cattle. As FGF18 expression is increased in atretic follicles, and as FGF18 protein inhibits estradiol secretion and induces apoptosis, we conclude that FGF18 plays a role in follicular atresia. Supported by NSERC Canada, CNPq and FAPESP, Brazil. (platform)
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Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
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