Roles for Golgi Glycans in Oogenesis and Spermatogenesis

Abstract

Glycosylation of proteins by N- and O-glycans or glycosaminoglycans (GAGs) mostly begins in the endoplasmic reticulum and is further orchestrated in the Golgi compartment via the action of >100 glycosyltransferases that reside in this complex organelle. The synthesis of glycolipids occurs in the Golgi, also by resident glycosyltransferases. A defect in the glycosylation machinery may impair the functions of glycoproteins and other glycosylated molecules, and lead to a congenital disorder of glycosylation (CDG). Spermatogenesis in the male and oogenesis in the female are tightly regulated differentiation events leading to the production of functional gametes. Insights into roles for glycans in gamete production have been obtained from mutant mice following deletion or inactivation of genes that encode a glycosylation activity. In this review, we will summarize the effects of altering the synthesis of N-glycans, O-glycans, proteoglycans, glycophosphatidylinositol (GPI) anchored proteins, and glycolipids during gametogenesis in the mouse. Glycosylation genes whose deletion causes embryonic lethality have been investigated following conditional deletion using various Cre recombinase transgenes with a cell-type specific promoter. The potential effects of mutations in corresponding glycosylation genes of humans will be discussed in relation to consequences to fertility and potential for use in contraception.

Keywords: Golgi; fertility; glycans; glycosylation; oogenesis; spermatogenesis.

FIGURE 1

Cell Surface Glycans in Mammals. The diagram depicts one or more glycans from each class of mammalian glycan. The diagram is modified from Figure in Stanley (2016) with permission. Sugar symbols are according to the Symbol Nomenclature for Glycans (Varki et al., 2015).

FIGURE 2

Oogenesis in Mammals. The diagram describes the different stages of oogenesis and identifies the follicular stage in which the ZP3 and Vasa promoters are active in oocytes. Both these promoters are used for oocyte-specific deletion by Cre recombinase. The diagram is modified from (Zhao and Dean, 2002) with permission.

FIGURE 3

Spermatogenesis in Mammals. The diagram describes germ cell differentiation during spermatogenesis and identifies the germ cell type in which different promoters are active. 2n diploid; 4n, tetraploid; 1n haploid.

FIGURE 4

Glycans required for spermatogenesis or oogenesis. Summary of known roles for individual glycans in mouse gametogenesis (see main text). (A) N-glycan maturation; (B) O-GalNAc core 1 and core 2 glycan synthesis; (C) Glycolipid synthesis; (D) Seminolipid synthesis; (E) O-Fucose glycan synthesis; (F) Chondroitin sulfate synthesis. X indicates a defect in male or female gametogenesis and √ indicates no known defect when related gene is deleted; Cer, ceramide; Eag, alkylacylglycerol. Sugar symbols are according to the Symbol Nomenclature for Glycans (Varki et al., 2015).