Impact of Hyaluronidase-1 and Hyaluronidase-3 Deficiency on Mouse Female Reproduction.
Notice bibliographique
Résumé
Mammalian hyaluronidases (EC 3.2.1.35) are endo-β-N-acetyl-hexosaminidases, that hydrolyze hyaluronic acid (hyaluronan), and to a lesser extent chondroitin and chondroitin sulfate, to generate mostly tetra-saccharides. In the ovary, expression of three hyaluronidases (Hyal-1, Hyal-2 and Hyal-3) has been documented and our group has recently shown that these enzymes are predominantly expressed in granulosa cells and are involved in follicular atresia. Interestingly, we found Hyal-1 to be preferentially expressed in small antral follicles of immature mice, and to be repressed in gonadotropin-responsive follicles. In addition, we showed that expression of all three hyaluronidases induced granulosa cell apoptosis via activation of the extrinsic apoptotic signaling pathway, although enzymatic activity was not required for this apoptosis induction. It is possible that a direct binding of hyaluronidases to specific protein partners would trigger the apoptotic signaling pathway. In the present work, we investigated the impact of Hyal-1 and Hyal-3 deficiency in female reproduction. Using our established mouse model for ovarian atresia (gonadotropin withdrawal by anti-eCG treatment), we showed that Hyal-1 but not Hyal-3 null mice have decreased apoptotic granulosa cells after atresia induction. Moreover, these Hyal-1 null mice (but not the Hyal-3 null animals) had increased number of retrieved oocytes after ovulation stimulation. Furthermore, young Hyal-1 null mice have significantly higher number of primordial follicles than age matched wild-type animals. Recruitment of these follicles at puberty resulted in increased number of primary and secondary follicles in 6-week-old null mice, but not in animals older than 6 months. These results indicate that Hyal-1 plays a role in the initial phase of follicle recruitment in young mice. Significantly, we observed increased levels of anti-Mullerian hormone (AMH) mRNA expression in pre-pubertal Hyal-1 null mice when compared to wild-type animals. Collectively, our findings indicate that Hyal-1 but not Hyal-3 has an important role in ovarian folliculogenesis and atresia. We suggest that induction of granulosa cell apoptosis by hyaluronidase-1 on follicles of immature mice is an important step for the control of initial primordial follicle recruitment. This enzyme might play a key role in the early phases of folliculogenesis by negatively regulating ovarian follicle growth and survival. Regulatory mechanisms involving expression of intra-ovarian factors of the TGFβ superfamily would participate in this process. Up to now, physiological roles of hyaluronidases in reproduction have been described only for testicular hyaluronidases (e.g. PH20/Spam1, Hyal-5, and Hyalp1), which have sperm-fertilizing ability by dispersing the cumulus layers of the ovulated cumulus-oocyte complex. Our results add somatic hyaluronidases as new players in ovarian folliculogenesis. Supported by NSERC (Natural Sciences and Engineering Research Council of Canada) (platform)
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Comment cette classification a été obtenuedéplier
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 | 0,001 | 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.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».