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1.
Birth Defects Res B Dev Reprod Toxicol ; 92(6): 526-33, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21922642

RESUMO

The objective of this study was to determine whether in utero exposure to Bisphenol A (BPA) induced reproductive tract abnormalities in the adult male testis. Using the C57/Bl6 mouse, we examined sex-organ weights, anogenital distance, and testis histopathology in adult males exposed in utero via oral gavage to sesame oil, 50 µg/kg BPA, 1000 µg/kg BPA, or 2 µg/kg diethylstilbestrol (DES) as a positive control from gestational days 10 to 16. No changes in sperm production or germ cell apoptosis were observed in adult testes after exposure to either chemical. Adult mRNA levels of genes associated with sexual maturation and differentiation, GATA4 and ID2, were significantly lower only in DES-exposed testes. In summary, the data indicate no gross alterations in spermatogenesis after in utero exposure to BPA or DES. At the molecular level, in utero exposure to DES, but not BPA, leads to decreased mRNA expression of genes associated with Sertoli cell differentiation.


Assuntos
Dietilestilbestrol/toxicidade , Estrogênios não Esteroides/toxicidade , Fenóis/toxicidade , Efeitos Tardios da Exposição Pré-Natal , Reprodução/efeitos dos fármacos , Testículo/efeitos dos fármacos , Útero/efeitos dos fármacos , Animais , Apoptose , Compostos Benzidrílicos , Western Blotting , Células Cultivadas , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Gravidez , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Células de Sertoli/citologia , Células de Sertoli/efeitos dos fármacos , Células de Sertoli/metabolismo , Maturidade Sexual/efeitos dos fármacos , Espermatogênese/efeitos dos fármacos
2.
Reprod Toxicol ; 31(1): 17-25, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-20951798

RESUMO

Exposure to 6-propyl-2-thio-uracil (PTU), a neonatal goitrogen, leads to increased testis size and sperm production in rodents. Akt1, a gene involved in cell survival and proliferation is also phosphorylated by thyroxine (T(4)). Therefore, we examined the requirement for Akt1 in germ cell survival following PTU-induced hypothyroidism. Experiments were performed using Akt1+/+, Akt1+/-, and Akt1-/- mice. PTU was administered (0.01% w/v) via the drinking water of dams from birth to PND21. At PND15, T(4) serum levels were similar in all control groups, and significantly lower in all exposed groups with a dramatic decrease in Akt1-/- mice. PTU-exposed Akt1-/- testes displayed smaller tubules, increased apoptosis, delayed lumen formation, and increased inhibin B and AMH mRNA. Relative adult testis weights were similar in all exposure groups; however, no increase in daily sperm production was observed in PTU-exposed Akt1-/- mice. In conclusion, Akt1 contributes to the effects of thyroid hormone on postnatal testis development.


Assuntos
Antitireóideos/toxicidade , Apoptose/efeitos dos fármacos , Exposição Materna/efeitos adversos , Propiltiouracila/toxicidade , Proteínas Proto-Oncogênicas c-akt/genética , Espermatozoides/efeitos dos fármacos , Testículo/efeitos dos fármacos , Animais , Animais Recém-Nascidos , Hormônio Antimülleriano/metabolismo , Apoptose/genética , Feminino , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Hipotireoidismo/induzido quimicamente , Hipotireoidismo/metabolismo , Hipotireoidismo/patologia , Inibinas/metabolismo , Lactação/efeitos dos fármacos , Lactação/fisiologia , Tamanho da Ninhada de Vivíparos/efeitos dos fármacos , Masculino , Camundongos , Camundongos Knockout , Tamanho do Órgão/efeitos dos fármacos , Gravidez , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Mensageiro/metabolismo , Células de Sertoli/efeitos dos fármacos , Células de Sertoli/patologia , Espermatozoides/patologia , Testículo/metabolismo , Testículo/patologia , Tri-Iodotironina/sangue
3.
Biol Reprod ; 82(2): 246-56, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19794155

RESUMO

Mammalian females are endowed with a finite number of primordial follicles at birth. Immediately following formation of the primordial follicle pool, cohorts of follicles are either culled from the ovary or are recruited to grow until the primordial follicle population is depleted. The majority of ovarian follicles, including the oocytes, undergo atresia through apoptotic cell death. As PKB alpha/Akt1 is known to regulate apoptosis, we asked whether Akt1 functioned in the regulation of folliculogenesis in the ovary. Akt1(-/-) females display reduced fertility and abnormal estrous cyclicity. At Postnatal Day (PND) 25, Akt1(-/-) ovaries possessed a reduced number of growing antral follicles, significantly larger primary and secondary oocytes, and an increase in the number of degenerate oocytes. By PND90, there was a significant decrease in the number of primordial follicles in Akt1(-/-) ovaries relative to Akt1(+/+). In vivo granulosa cell proliferation was reduced, as were expression levels of Kitl and Bcl2l1, two factors associated with granulosa cell proliferation/survival. No compensation was observed by Akt2 or Akt3 at the mRNA/protein level. Significantly higher serum LH and trends for lower FSH and higher inhibin A and lower inhibin B relative to Akt1(+/+) females were observed in Akt1(-/-) females. Exposure to exogenous gonadotropins resulted in an increase in the number of secondary follicles in Akt1(-/-) ovaries, but few mature follicles. Collectively, our results suggest that PKB alpha/Akt1 plays an instrumental role in the regulation of the growth and maturation of the ovary, and that the loss of PKB alpha/Akt1 results in premature ovarian failure.


Assuntos
Infertilidade Feminina/etiologia , Oócitos/crescimento & desenvolvimento , Folículo Ovariano/crescimento & desenvolvimento , Proteínas Proto-Oncogênicas c-akt/deficiência , Animais , Peso Corporal , Cruzamento , Ciclina D/análise , Ciclina D/genética , Estradiol/sangue , Ciclo Estral , Feminino , Masculino , Camundongos , Camundongos Knockout , Oócitos/citologia , Tamanho do Órgão , Folículo Ovariano/química , Ovário/química , Ovário/metabolismo , Ovário/patologia , Progesterona/sangue , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/fisiologia , RNA Mensageiro/análise , Maturidade Sexual/fisiologia , Esteroides/biossíntese
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