Sugar-coated sperm: Unraveling the functions of the mammalian sperm glycocalyx

Abstract

Mammalian spermatozoa are coated with a thick glycocalyx that is assembled during sperm development, maturation, and upon contact with seminal fluid. The sperm glycocalyx is critical for sperm survival in the female reproductive tract and is modified during capacitation. The complex interplay among the various glycoconjugates generates numerous signaling motifs that may regulate sperm function and, as a result, fertility. Nascent spermatozoa assemble their own glycans while the cells still possess a functional endoplasmic reticulum and Golgi in the seminiferous tubule, but once spermatogenesis is complete, they lose the capacity to produce glycoconjugates de novo. Sperm glycans continue to be modified, during epididymal transit by extracellular glycosidases and glycosyltransferases. Furthermore, epididymal cells secrete glycoconjugates (glycophosphatidylinositol-anchored glycoproteins and glycolipids) and glycan-rich microvesicles that can fuse with the maturing sperm membrane. The sperm glycocalyx mediates numerous functions in the female reproductive tract, including the following: inhibition of premature capacitation; passage through the cervical mucus; protection from innate and adaptive female immunity; formation of the sperm reservoir; and masking sperm proteins involved in fertilization. The immense diversity in sperm-associated glycans within and between species forms a remarkable challenge to our understanding of essential sperm glycan functions.

Figure 1

The major glycan and glycoconjugate classes of the sperm glycocalyx. Monosaccharides are coded by colored symbols explained in the legend. Proteins and lipids are gray, except cholesterol (in yellow), and the lipids of glycosphingolipids (in orange). Mammals synthesize most glycans with a dozen different monosaccharide‐building blocks; some of these monosaccharides can be further modified by sulfation and/or acetylation.

Figure 2

Synthesis of major glycan classes in the endoplasmic reticulum/Golgi of nascent sperm, and subsequent modification in the lumen of the epididymis. Genes or names for glycosylation enzymes discussed in the text are highlighted in red.

Figure 3

Mammalian spermatogenesis. A: Spermatogenesis takes place in the seminiferous tubules inside the testes. B: Primordial germ cells (spermatogonia) differentiate into primary and secondary spermatids, spermatocytes, and spermatozoa. C: Sertoli cells provide the environment for successful spermatogenesis. D: Schematic of meioses I and II. E: Comparison of the levels of gene transcription and glycocalyx formation during sperm maturation, according to the parallel timelines of ‘C’ and ‘D’.

Figure 4

Functions of the sperm glycocalyx. A: N‐glycosylation‐dependent protein folding during spermatogenesis and spermatid‐Sertoli cell adhesion. B: Spatially defined sperm glycan modification in the epididymis. C: Seminal components added to the glycocalyx maintain sperm in a non‐capacitated, acrosome‐intact state. D: Cervical mucus transit requires sialylated beta‐ defensin glycoproteins in primates. E: Immune modulatory glycans, including “self‐associated molecular patterns” and immunosuppressive signals, aid sperm survival in the uterus. F: Sperm passage through the uterotubal junction facilitated by glycosylation‐dependent folding of ADAM proteins. G: Formation of the sperm reservoir by glycan‐dependent adherence of sperm to the oviductal epithelium. H: Loss of glycans, glycoproteins, and cholesterol during capacitation. I: Exposure of masked functional molecules on the sperm cell surface, due to loss of glycans and glycoconjugates, allow for sperm–egg interactions.