Beta-N-acetylhexosaminidase activity in human oocytes and preimplantation embryos.

beta-N-acetylhexosaminidase is a lysosomal enzyme, which has two isoenzymes: beta-Hex A, a trimer consisting of one alpha-chain and two beta-chains (alpha beta 2) and beta-Hex B, a tetramer formed of four beta-chains (beta 2 beta 2). Genetic defects in the alpha-chain lead to Tay-Sachs disease, whereas mutations in the beta-chain gene lead to Sandhoff disease. In a previous study we developed a microassay for total beta-N-acetylhexosaminidase and used this for measuring activities in mouse oocytes and preimplantation embryos. In this study, to assess the feasibility of transferring this technique to the human for the purposes of preimplantation diagnosis for Tay-Sachs and Sandhoff disease, beta-Hex activity was assayed in human oocytes and embryos and in the medium in which they had been cultured. We showed that although the activity of beta-N-acetylhexosaminidase in human oocytes and embryos was > 500 times higher than in the mouse, it was not detectable in the culture medium and the activity in oocytes and embryos remained virtually constant throughout human preimplantation development, making it difficult to distinguish embryonic from maternal enzyme activity. In the absence of this distinction it would be inappropriate to use beta-N-acetylhexosaminidase activity for the purposes of preimplantation diagnosis of Sandhoff or Tay-Sachs disease. These experiments demonstrate that measuring the beta-N-acetylhexosaminidase activity in human embryos cannot be used at present for preimplantation diagnosis.