The role of sperm proteasomes during sperm aster formation and early zygote development: Implications for fertilization failure in humans

VY RAWE,; ES DÍAZ,; R ABDELMASSIH,; C WÓJCIK,; P MORALES,; P SUTOVSKY,; HE CHEMES

Human Reproduction

Oxford University Press

Lugar: Oxford UK; Año: 2007

BACKGROUND: Sperm aster organization during bovine and human fertilization requires a paternally-derived centriole that must first disengage from the sperm tail connecting-piece. We investigated the participation of the 26S proteasome in this process. METHODS: Proteasome localization and enzymatic activity were studied innormal and pathological human spermatozoa by immunocytochemistry and enzyme-substrate assays. The role of proteasomes during bovine zygote development was investigated using a pharmacological proteasome-inhibitor, MG132, and with anti-proteasome antibodies delivered by Streptolysin O-permeabilization or with the Chariot reagent. Human zygotes discarded after ICSI failures (n 5 28) were also examined. RESULTS: Proteasomes were localized in the sperm acrosome and connecting-piece, as well as in the pronuclei of bovine and human zygotes. Proteasomal enzymatic activities were decreased in defective human spermatozoa. Disrupted sperm aster formation and pronucleardevelopment were found after pharmacological and immunological block of proteasomes in human/bovine spermatozoaand oocytes, as well as in 28 discarded human post-ICSI fertilization failures. CONCLUSIONS: Specific proteasome inhibition disrupts sperm aster formation and pronuclear development/apposition in bovine and human zygotes. Human spermatozoa with defective centriolar/pericentriolar structures have decreased proteasomal enzymatic activity. Release of a functional sperm centriole that acts as a zygote microtubule-organizing center probably relies on selective proteasomal proteolysis. These findings suggest an important role of sperm proteasomes in zygotic development.n 5 28) were also examined. RESULTS: Proteasomes were localized in the sperm acrosome and connecting-piece, as well as in the pronuclei of bovine and human zygotes. Proteasomal enzymatic activities were decreased in defective human spermatozoa. Disrupted sperm aster formation and pronucleardevelopment were found after pharmacological and immunological block of proteasomes in human/bovine spermatozoaand oocytes, as well as in 28 discarded human post-ICSI fertilization failures. CONCLUSIONS: Specific proteasome inhibition disrupts sperm aster formation and pronuclear development/apposition in bovine and human zygotes. Human spermatozoa with defective centriolar/pericentriolar structures have decreased proteasomal enzymatic activity. Release of a functional sperm centriole that acts as a zygote microtubule-organizing center probably relies on selective proteasomal proteolysis. These findings suggest an important role of sperm proteasomes in zygotic development.