Antiacrosin antibodies and infertility. II: gene immunization with human proacrosin to assess the effect of immunity toward proacrosin/acrosin upon protein activities and animal fertility
Objective: To assess the effect of antiacrosin antibodies upon proacrosin/acrosin activities and animal fertility. Design: Prospective study. Setting: Basic research laboratory. Patient(s): A gene immunization (GI) model was developed; mice were injected with the sequence encoding human proacrosin (...
| Autores: | , , , , |
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| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2008 |
| País: | Argentina |
| Institución: | Consejo Nacional de Investigaciones Científicas y Técnicas |
| Repositorio: | CONICET Digital (CONICET) |
| Idioma: | inglés |
| OAI Identifier: | oai:ri.conicet.gov.ar:11336/24462 |
| Acceso en línea: | http://hdl.handle.net/11336/24462 |
| Access Level: | acceso abierto |
| Palabra clave: | Proacrosin Spermatozoa Gene Immunization Antisperm Antibodies Acrosin https://purl.org/becyt/ford/1.6 https://purl.org/becyt/ford/1 |
| Sumario: | Objective: To assess the effect of antiacrosin antibodies upon proacrosin/acrosin activities and animal fertility. Design: Prospective study. Setting: Basic research laboratory. Patient(s): A gene immunization (GI) model was developed; mice were injected with the sequence encoding human proacrosin (h-proacrosin), cloned in an expression vector. Intervention(s): Subcloning of h-proacrosin in a eukaryotic expression vector (promoter, CMV; leader sequence, a-1 antitrypsin; pSF2-Acro); GI of female mice with this plasmid. Main Outcome Measure(s): The following parameters were evaluated: [1] adequate conditions for GI protocols, [2] humoral response to GI with pSF2-Acro, [3] protein regions recognized by the antibodies, and [4] effect of antibodies upon proacrosin/acrosin–ZPA binding and amidase activity, and animal fertility. Result(s): Conditions of female mice GI with the proacrosin sequence were established (plasmid purification with anion exchange chromatography and 40 mg of pSF2-Acro per dose) to trigger an immune response, reaching maximum levels at week 9 after the first injection. Antibodies produced by GI recognized human and mouse sperm acrosin systems, inhibited human proacrosin/acrosin interaction with recombinant human ZPA and protease activity, and negatively affected mouse IVF and early embryonic development. In addition, mice immunized with SF2-Acro exhibited a significantly lower size of fetuses. Conclusion(s): Antiacrosin antibodies developed by using GI inhibit human proacrosin/acrosin activities and impair mouse fertility. |
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