The Threshold of Spermatogonial Stem Cell Numbers That Allows Male Fertility Restoration in Mice after a Treatment with an Alkylating Agent, Busulfan.
Notice bibliographique
Résumé
As the cancer survival rate has been increasing steadily in recent years, the risk of infertility induced by anti-cancer regimen has become a significant concern for the quality of post-cancer life. Spermatogonial stem cells (SSCs) constitute the foundation of spermatogenesis and represent a crucial resource for the male fertility restoration. Using the mouse as a model, we investigated in this study the cytotoxic effect on SSCs of an alkylating agent, busulfan, and correlated the kinetics of SSC loss and proliferation with those of male fertility loss and restoration. We treated male transgenic mice, which carry LacZ in all male germ cells, with busulfan at three doses (15, 30 and 45 mg/kg) and examined their fertility by mating with intact females at different times post treatment. We measured SSC numbers by a transplantation assay using immunocompatible recipient mice. Colonies of donor-derived spermatogenesis were visualized by incubating recipient testes with 5-bromo-4chloro-3-indolyl β-galactosidase (X-gal) to determine the number of functional donor SSCs at each time point. We also measured testis weights and sperm counts and assessed spermatogenic recovery in histology. We found that fertility was lost within 4 weeks after treatment, regardless of busulfan doses. However, most SSCs were lost (>95%) in a dose-dependent manner within 3 days after treatment. Male fertility was restored in 12 weeks following treatment with 15 mg/kg busulfan, while 26 and 30 weeks were required when the males received 30 and 45 mg/kg busulfan, respectively, demonstrating a dose-dependent effect on SSC recovery. Interestingly, however, SSC numbers reached 30% of the before-treatment level by 4 weeks prior to the time of fertility restoration, regardless of busulfan doses (i.e., 8, 22, and 26 weeks with 15, 30, and 45 mg/kg busulfan, respectively). In agreement with these results, testis weights and spermatogenic recovery showed a dose-dependent effect of busulfan and its preferential killing of SSCs. The results of sperm counts showed that 17.5% of the before-treatment sperm number is required to grant fertility in mice, below which mice remained infertile. These results demonstrate that the loss and restoration of fertility after busulfan treatment are a direct consequence of SSC loss and proliferation. Importantly, the fact that the SSC numbers at 4 weeks before fertility recovery are nearly identical across the busulfan doses used indicate that there is a threshold in SSC numbers that allows the restoration of male fertility, which is 30% of the initial SSC numbers. In addition, these results set 17.5% of sperm count as a critical size of sperm population that allows male fertility in mice. (poster)
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| 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 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,002 | 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 source (Gemma direct ou Codex distillé), 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 ».