1 LONG TERM HEALTH AND BEHAVIOR OF ICSI PRODUCED MICE
Notice bibliographique
Résumé
Intracytoplasmic sperm injection (ICSI) is a relatively new treatment for human male-related infertility (1992) and for the production of transgenic animals (1995). However, ICSI bypasses many natural biological processes such as sperm maturation, interaction within the female genital tract, sperm capacitation, interaction with oocyte vestments, and sperm membrane fusion with the oocyte. With the widespread use of this technology, its potential adverse outcomes need to be ascertained. It is theoretically possible that ICSI may cause specific problems through injury to the sperm or egg or injection of damaged or defective sperm. Here, we determined if ICSI has a long-term effect on mouse growth, behavior, and health. Female CD1 mice were superovulated and oocytes were injected with frozen-thawed spermatozoa (without cryoprotector or chelating agent) obtained from CD1 mice epididymes (Moreira et al. 2004 Biol. Reprod. 71, in press). Embryos were cultured 24 h in KSOM, and 2-cell embryos were transferred into CD1 females. Fifty-six mice (36 males and 20 females) produced by ICSI and 41 control mice (18 males and 23 females) obtained from in vivo-fertilized mice were analyzed. On week 20, animals were submitted to the following behavior tests: locomotor activity (open field), exploratory/anxiety behavior (elevated plus maze, open field), and spatial memory (free-choice exploration paradigm in Y maze). Comparison between groups was made using analysis of variance followed by least significant difference post hoc test. Postnatal weight gain of female mice produced by ICSI was heavier than for their control counterparts from 10 weeks on (P < 0.01). Males produced by ICSI showed more anxiety and lower locomotion in the p-maze and the Y-maze tests (P < 0.05), but no significant differences were found in the open-field test. Also, no differences were found in spatial memory or in the habituation pattern. Anatomopathological analysis of animals at 16 months of age showed some large organs (heart, lung, and liver; P < 0.01) and an increase in pathologies (15% of animals produced by ICSI presented some solid tumors in lung, dermis of back, or neck). Loss of imprinting is one of the most common epigenetic changes associated with the development of a wide variety of tumours. An association between some imprinting disorders, rare tumors, and ICSI has recently been reported in humans (Wittermer et al. 2004 Med. Sci. 20, 352). We are now analyzing the epigenetic modifications that may be induced by our ICSI protocol and whether the sperm DNA fragmentation that may take place during sperm freezing before the ICSI procedure might not only affect postnatal development, growth, and physiology, but also increase the risk of tumors in adult animals. Our data suggest that our ICSI method produces mice with sex-dimorphic alterations in aberrant growth and anxiety, as well as with a higher probability of developing a solid tumor.
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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 ».