ZP2 peptide beads select human sperm in vitro, decoy mouse sperm in vivo, and provide reversible contraception
| Autor: | Anna Burkart Sadusky, Matteo Alessandro Avella, María Jiménez-Movilla, Jurrien Dean, Boris Baibakov |
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| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Male endocrine system Peptide Reproductive technology Fertilization in Vitro Biology Article Andrology 03 medical and health sciences Mice Human fertilization In vivo medicine Animals Humans Acrosome Zona pellucida reproductive and urinary physiology Zona Pellucida Ovum chemistry.chemical_classification urogenital system General Medicine Sperm Spermatozoa 030104 developmental biology medicine.anatomical_structure Contraception chemistry Fertilization Oviduct Female Peptides |
| Zdroj: | Science translational medicine. 8(336) |
| ISSN: | 1946-6242 |
| Popis: | Gamete recognition in the female reproductive tract occurs at the surface of the zona pellucida surrounding ovulated eggs. The acellular zona matrix is composed of three (mouse) or four (human) proteins (ZP1 to ZP4), and the amino terminus of ZP2 is the primary sperm-binding ligand. Mouse and human sperm bind, respectively, to recombinant moZP2(35-149) and huZP2(39-154) peptides attached to agarose beads. Mouse ZP2 peptide beads markedly inhibited fertilization of ovulated mouse eggs inseminated in vitro and incubated overnight. Similarly, human ZP2 peptide beads prevented sperm binding and penetration of transgenic ZP2(Rescue) zonae pellucidae, in which human ZP2 replaced mouse ZP2. When mouse ZP2 peptide beads were transcervically deposited into the uterus, there was no change in mating behavior and copulatory plugs were present, but bound sperm did not progress into the oviduct and female mice were infertile. On average, contraception lasted >10 estrus cycles but was reversible with no detectable pathology in the reproductive tract. Despite the long-term contraceptive effect, initial sperm binding to the peptide beads was reversible in vitro. We exploited this observation to select human sperm that were better able to penetrate the zonae of human ZP2(Rescue) eggs, and the approach holds promise for identifying superior sperm for human assisted reproductive technologies (ART). We conclude that the amino-terminal ZP2 peptide supports sperm binding, which is initially reversible but, with time, becomes irreversible. Short-term, reversible binding may be useful in selecting sperm for ART, and long-term binding decoys sperm and results in effective contraception in mice. |
| Databáze: | OpenAIRE |
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