227 AN ALTERATION IN GENE EXPRESSION PATTERNS INDUCED BY DI-(2 ETHYLHEXYL) PHTHALATE AND FLUTAMIDE IN THE TESTIS OF IMMATURE MALE RATS
Notice bibliographique
Résumé
In a previous study, we demonstrated that although endocrine disruptors (EDs) with androgenic and anti-androgenic effects may alter reproductive function, their effects on the developing male reproductive organs may be distinct. To continue this line of study, we treated immature rats to examine the adverse effects of di-(2 ethylhexyl) phthalate (DEHP) and flutamide (Flu) on the male reproductive system. Immature male SD rats were treated daily with DEHP and/or Flu at postnatal day (PND) 21 to 35 in a dose-dependent manner, and the changes evoked by these EDs were determined by differences in male reproductive tract and other organ weights, testicular histology, and serum LH and testosterone levels in combination with global microarray analysis. Interestingly, the testes, prostate, seminal vesicle weight, and anogenital distances were significantly decreased in response to the highest dose of DEHP and Flu. There were no differences in serum LH and testosterone concentration at PND 35 for immature male rats exposed to DEHP and/or Flu. However, treatment with DEHP and/or Flu caused histopathological changes in testes in which the degeneration and denseness of germ cells and/or dilatation of the tubular lumen were observed in response to the high dose [500 mg kg–1 of body weight (BW)] of DEHP and medium dose (10 mg kg–1 of BW) of Flu. Additionally, the results from cDNA microarray indicated that 1272 genes were up-regulated (more than 2-fold) and 1969 genes were down-regulated in response to DEPH and/or Flu. These genes were identified based on their roles in some physiological processes (i.e. lipid and cholesterol homeostasis, steroidogenesis, sex determination, and calcium signal transduction). The significant decreases were observed in the expressions of steroidogenic genes (i.e. Star, Cyp11a1, or Hsd3b). In addition, a common set of targeting genes, including CaBP1, Vav2, Plcd1, Lhx1, and Isoc1, were altered following EDs exposure, suggesting a potential set of biomarker genes for screening anti-androgenic and/or androgenicity of EDs. Taken together, we demonstrated that exposure to DEHP and/or Flu resulted in a temporal alteration in gene expression profile in the testes of immature male rats, and their toxicological effects on male reproductive system are distinct depending on their anti-androgenicity, suggesting new insight into molecular mechanism(s) underlying detrimental impacts of EDs with anti-androgenic activities in human and wildlife.
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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 | 0,000 | 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.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».