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Sci Total Environ ; 274(1-3): 103-13, 2001 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-11453286


The response from exposure to a toxic agent during development may vary depending on the dose, time of exposure and the mode of action. The mode of action and developmental stage sensitivity are established only for a limited number of chemical classes. Some aspects of developmental stage sensitivity that appear to affect the response to androgen agonists and antagonists are the levels and distribution of endogenous androgens and the androgen receptor at particular times during development. This information is summarized and discussed as it relates to two critical windows of development: the period of male reproductive tract differentiation, and the peripubertal period when male sexual maturation occurs. Developmental stage sensitivity and mode of action data for the androgen antagonist vinclozolin are reviewed. Vinclozolin acts by binding to and activating the androgen receptor and affects a number of endpoints of reproductive tract differentiation as well as pubertal maturation. Approaches to incorporating mode of action, developmental stage sensitivity, and dose/potency information into risk assessment, as well as the additional data needed for using mode of action information, both qualitatively and quantitatively, in risk assessment are discussed. These issues are also considered in the context of combining the risks of exposure to two or more chemicals with similar modes of action.

Antagonistas de Androgênios/toxicidade , Androgênios/agonistas , Exposição Ambiental/efeitos adversos , Envelhecimento , Androgênios/fisiologia , Animais , Desenvolvimento Embrionário e Fetal/efeitos dos fármacos , Fungicidas Industriais/toxicidade , Idade Gestacional , Humanos , Masculino , Mamíferos , Oxazóis/toxicidade , Receptores Androgênicos/fisiologia
Dev Biol ; 206(2): 142-56, 1999 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-9986728


The Caenorhabditis elegans gene lin-29 encodes a zinc-finger transcription factor that is required for hypodermal cell terminal differentiation and proper vulva morphogenesis. Here we demonstrate that lin-29 is also required in males for productive mating. We show that lin-29 males can perform the early mating behaviors including response to hermaphrodite contact and vulva location, but they do not perform the subsequent steps of vulva attachment via spicule insertion and sperm transfer. Consistent with this observation, we found that lin-29 mutant spicules are on average 43% shorter than wild-type spicules while other male mating structures appear unaltered. In lin-29 mutants, spicule development goes awry after the generation of spicule cells, when spicule morphogenesis occurs in wild-type males. We show that LIN-29 accumulates in many cells of the wild-type male tail, including those that form the spicules. We demonstrate, through analysis of genetic mosaics, that the formation of wild-type-length spicules requires lin-29(+) in the AB.p lineage, the lineage that gives rise to the spicules and other male copulatory structures. Our mosaic analysis also reveals a role for lin-29(+) in the P1 lineage, which mainly produces sex muscles, cells of the somatic gonad, and body wall muscles.

Proteínas de Caenorhabditis elegans , Caenorhabditis elegans/crescimento & desenvolvimento , Proteínas de Ligação a DNA/fisiologia , Proteínas de Helminto/fisiologia , Proteínas Nucleares , Cauda/crescimento & desenvolvimento , Fatores de Transcrição/fisiologia , Animais , Caenorhabditis elegans/genética , Caenorhabditis elegans/fisiologia , Proteínas de Ligação a DNA/genética , Feminino , Regulação da Expressão Gênica no Desenvolvimento , Genes de Helmintos , Proteínas de Helminto/genética , Masculino , Mosaicismo , Mutação , Comportamento Sexual Animal/fisiologia , Cauda/fisiologia , Fatores de Transcrição/genética
Development ; 124(21): 4333-42, 1997 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-9334281


Caenorhabditis elegans vulval development culminates during exit from the L4-to-adult molt with the formation of an opening through the adult hypodermis and cuticle that is used for egg laying and mating. Vulva formation requires the heterochronic gene lin-29, which triggers hypodermal cell terminal differentiation during the final molt. lin-29 mutants are unable to lay eggs or mate because no vulval opening forms; instead, a protrusion forms at the site of the vulva. We demonstrate through analysis of genetic mosaics that lin-29 is absolutely required in a small subset of lateral hypodermal seam cells, adjacent to the vulva, for wild-type vulva formation and egg laying. However, lin-29 function is not strictly limited to the lateral hypodermis. First, LIN-29 accumulates in many non-hypodermal cells with known roles in vulva formation or egg laying. Second, animals homozygous for one lin-29 allele, ga94, have the vulval defect and cannot lay eggs, despite having a terminally differentiated adult lateral hypodermis. Finally, vulval morphogenesis and egg laying requires lin-29 activity within the EMS lineage, a lineage that does not generate hypodermal cells.

Proteínas de Caenorhabditis elegans , Caenorhabditis elegans/crescimento & desenvolvimento , Caenorhabditis elegans/genética , Proteínas de Ligação a DNA/genética , Oviposição/fisiologia , Fatores de Transcrição/genética , Vulva/crescimento & desenvolvimento , Animais , Diferenciação Celular/genética , Fusão Celular/genética , Códon de Terminação , Feminino , Larva , Mosaicismo , Mutação , Fenótipo , Útero/crescimento & desenvolvimento
Development ; 122(8): 2507-15, 1996 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-8756295


In Caenorhabditis elegans, the fates of the multipotent vulval precursor cells (VPCs) are specified by intercellular signals. The VPCs divide in the third larval stage (L3) of the wild type, producing progeny of determined cell types. In lin-28 mutants, vulva development is similar to wild-type vulva development except that it occurs precociously, in the second larval stage (L2). Consequently, when lin-28 hermaphrodites temporarily arrest development at the end of L2 in the dauer larva stage, they have partially developed vulvae consisting of VPC progeny. During post-dauer development, these otherwise determined VPC progeny become reprogrammed back to the multipotent, signal-sensitive state of VPCs. Our results indicate that VPC fate determination by intercellular signals is reversible by dauer larva developmental arrest and post-dauer development.

Caenorhabditis elegans/embriologia , Células-Tronco/citologia , Animais , Caenorhabditis elegans/citologia , Diferenciação Celular , Divisão Celular , Linhagem Celular , Feminino , Proteínas de Helminto/metabolismo , Transdução de Sinais , Vulva/citologia , Vulva/embriologia
Cell ; 84(5): 667-76, 1996 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-8625405


Heterochronic genes control the timing of vulval development in the C. elegans hermaphrodite. lin-14 or lin-28 loss-of-function mutations cause the vulval precursor cells (VPCs) to enter S phase and to divide one larval stage earlier than in the wild type. A precocious vulva is formed by essentially normal cell lineage patterns, governed by the same intercellular signals as in the wild type. Mutations that prevent the normal developmental down-regulation of lin-14, activity delay or block VPC division and prevent vulval differentiation. A genetic pathway that includes lin-4, lin-14, and lin-28 controls when VPCs complete G1 and also controls when VPCs acquire the competence to respond to the intercellular patterning signals and express vulval fates.

Caenorhabditis elegans/crescimento & desenvolvimento , Caenorhabditis elegans/genética , Genes de Helmintos , Vulva/crescimento & desenvolvimento , Animais , Diferenciação Celular , Divisão Celular , Núcleo Celular/fisiologia , DNA de Helmintos/análise , Feminino , Expressão Gênica , Genótipo , Hidroxiureia/farmacologia , Mutação , Fenótipo , Proteínas Recombinantes/biossíntese , Temperatura , Fatores de Tempo , Vulva/citologia , beta-Galactosidase/análise , beta-Galactosidase/biossíntese