Spermatogenesis-defective (spe) mutants of the nematode Caenorhabditis elegans provide clues to solve the puzzle of male germline functions during reproduction

Abstract

In most species, each sex produces gametes, usually either sperm or oocytes, from its germline during gametogenesis. The sperm and oocyte subsequently fuse together during fertilization to create the next generation. This review focuses on spermatogenesis and the roles of sperm during fertilization in the nematode Caenorhabditis elegans, where suitable mutants are readily obtained. So far, 186 mutants defective in the C. elegans male germline functions have been isolated, and many of these mutations are alleles for one of the approximately 60 spermatogenesis-defective (spe) genes. Many cloned spe genes are expressed specifically in the male germline, where they play roles during spermatogenesis (spermatid production), spermiogenesis (spermatid activation into spermatozoa), and/or fertilization. Moreover, several spe genes are orthologs of mammalian genes, suggesting that the reproductive processes of the C. elegans and the mammalian male germlines might share common pathways at the molecular level.

Fig. 1

The two sexes of the nematode C. elegans. Top: An adult hermaphrodite has a two-armed gonad that exhibits mirror image symmetry around the single vulval opening. The location of each spermatheca is outlined by red squares. Numbers below the gonad indicate the positions of oocytes according to their developmental stages. Bottom: An adult male has a one-armed gonad. Spermatids accumulate in the single vas deferens until they are ejaculated during mating with a hermaphrodite.

Fig. 2

The three central stages of male germline functions. A: Spermatogenesis. B: Spermiogenesis. C: Fertilization. A blue square shows that a sperm contacts the oocyte plasma membrane through its pseudopod. In these figures, the approximate point where a spe gene is first observed to act (by light microscopy) is indicated in red letters.

Fig. 3

FB-MO morphogenesis during spermatogenesis and spermiogenesis. A: The cytological stages of spermatogenesis and spermiogenesis, and how they are coordinated with FB-MO morphogenesis. B: The stages of FB-MO morphogenesis. Red, wavy lines represent the contents of the MO vesicles, which are released into the extracellular space upon spermiogenesis. Blue lines show polymerized or de-polymerized MSP filaments. These figures are meant to show the fundamental process of FB-MO morphogenesis, so some details are simplified.

Fig. 4

Two predicted pathways for spermiogenesis. Spermatids from hermaphrodites and males probably each have a distinct pathway for spermiogenesis. One pathway is spe-8 class-dependent (surrounded by broken or solid orange line) and another is spe-8 class-independent (broken or solid light blue line). A decision to utilize either pathway might depend on activators that are sex-specific. The spe-8 class-dependent pathway seems to be stimulated by a hermaphrodite-derived activator(s) or the serine protease mixture Pronase, whereas male-derived serine proteases that are targets of the trypsin inhibitor-like protein SWM-1 utilize the spe-8 class-independent pathway. To initiate spermiogenesis, these activators might be required to cleave a certain cell-surface protein(s). There seem to be other possible ways to initiate spermiogenesis. For example, serine proteases targeted by SWM-1 might process a precursor protein(s) of the actual activator(s) for spermiogenesis. The SPE-6 kinase is downstream of SPE-8 class proteins and is one of the common points between these two pathways. This kinase phosphorylates (shown as “P” in a light orange ball) unknown substrate(s), and the phosphorylated protein then plays a role in signal transduction to block onset of spermiogenesis. The signal might affect the SPE-4 presenilin and presumably other proteins (purple and blue diamonds; the precise number is unknown). During spermiogenesis, SPE-6 activity is reduced so that negative regulatory proteins such as SPE-4 cannot function to block spermiogenesis. In this figure, the active and inactive status are shown by solid and broken lines, respectively. Thick, black arrows represent positive regulation, whereas negative regulation is expressed by T-shaped lines. PM, plasma membrane.

Fig. 5

SPE-9 class proteins presumably required for sperm-oocyte interactions. A: SPE-9. E, EGF-like domain. B: SPE-42. The region corresponding to the DC-STAMP domain is indicated by a broken purple line. C: SPE-38. D: SPE-41/TRP-3. In these figures, predicted functions are highlighted by orange letters. Blue cylinders represent the transmembrane domains. PM, plasma membrane.