Roles for Glycans in Mammalian Development and Spermatogenesis

Abstract

N‐ and O‐glycans of mammalian glycoproteins play numerous roles within the secretory pathway and at the cell surface. Thus, deletion of a glycosyltransferase responsible for the synthesis of major classes of glycans usually leads to embryonic death. To identify roles for specific glycans in spermatogenesis, conditional deletion in spermatogonia was performed using males transgenic for Stra8‐iCre recombinase. All male germ cells derive from spermatogonia via differentiation in close association with Sertoli cells to sperm. Of three glycosyltransferase genes inactivated, only conditional deletion of Mgat1, encoding the glycosyltransferase that initiates complex N‐glycan synthesis, disrupted spermatogenesis. A block at the post‐meiotic spermatid stage resulted in male infertility. Interestingly, at an earlier stage of spermatogenesis, Mgat1 gene expression is downregulated in spermatocytes, and expression of a physiological inhibitor of MGAT1 transferase activity, termed GnT1IP‐L, is upregulated. We are testing the hypothesis that high mannose N‐glycans expressed on germ cell glycoproteins when Mgat1 is downregulated and the GnT1IP‐L gene is expressed, are required for spermatocyte/Sertoli cell interactions; while complex N‐glycans, generated when Mgat1 is upregulated and GnT1IP‐L is low, are required for spermatids to differentiate into spermatozoa.