Egg toxic compounds in the animal kingdom. A comprehensive review.

Covering: 1951 to 2022Packed with nutrients and unable to escape, eggs are the most vulnerable stage of an animal's life cycle. Consequently, many species have evolved chemical defenses and teamed up their eggs with a vast array of toxic molecules for defense against predators, parasites, or pathogens. However, studies on egg toxins are rather scarce and the available information is scattered. The aim of this review is to provide an overview of animal egg toxins and to analyze the trends and patterns with respect to the chemistry and biosynthesis of these toxins. We analyzed their ecology, distribution, sources, occurrence, structure, function, relative toxicity, and mechanistic aspects and include a brief section on the aposematic coloration of toxic eggs. We propose criteria for a multiparametric classification that accounts for the complexity of analyzing the full set of toxins of animal eggs. Around 100 properly identified egg toxins are found in 188 species, distributed in 5 phyla: cnidarians (2) platyhelminths (2), mollusks (9), arthropods (125), and chordates (50). Their scattered pattern among animals suggests that species have evolved this strategy independently on numerous occasions. Alkaloids are the most abundant and widespread, among the 13 types of egg toxins recognized. Egg toxins are derived directly from the environment or are endogenously synthesized, and most of them are transferred by females inside the eggs. Their toxicity ranges from ρmol kg-1 to mmol kg-1, and for some species, experiments support their role in predation deterrence. There is still a huge gap in information to complete the whole picture of this field and the number of toxic eggs seems largely underestimated.

Novel Role for Animal Innate Immune Molecules: Enterotoxic Activity of a Snail Egg MACPF-Toxin.

Gastropod Molluscs rely exclusively on the innate immune system to protect from pathogens, defending their embryos through maternally transferred effectors. In this regard, Pomacea snail eggs, in addition to immune defenses, have evolved the perivitellin-2 or PV2 combining two immune proteins into a neurotoxin: a lectin and a pore-forming protein from the Membrane Attack Complex/Perforin (MACPF) family. This binary structure resembles AB-toxins, a group of toxins otherwise restricted to bacteria and plants. Many of these are enterotoxins, leading us to explore this activity in PV2. Enterotoxins found in bacteria and plants act mainly as pore-forming toxins and toxic lectins, respectively. In animals, although both pore-forming proteins and lectins are ubiquitous, no enterotoxins have been reported. Considering that Pomacea snail eggs ingestion induce morpho-physiological changes in the intestinal mucosa of rodents and is cytotoxic to intestinal cells in culture, we seek for the factor causing these effects and identified PmPV2 from Pomacea maculata eggs. We characterized the enterotoxic activity of PmPV2 through in vitro and in vivo assays. We determined that it withstands the gastrointestinal environment and resisted a wide pH range and enzymatic proteolysis. After binding to Caco-2 cells it promoted changes in surface morphology and an increase in membrane roughness. It was also cytotoxic to both epithelial and immune cells from the digestive system of mammals. It induced enterocyte death by a lytic mechanism and disrupted enterocyte monolayers in a dose-dependent manner. Further, after oral administration to mice PmPV2 attached to enterocytes and induced large dose-dependent morphological changes on their small intestine mucosa, reducing the absorptive surface. Additionally, PmPV2 was detected in the Peyer's patches where it activated lymphoid follicles and triggered apoptosis. We also provide evidence that the toxin can traverse the intestinal barrier and induce oral adaptive immunity with evidence of circulating antibody response. As a whole, these results indicate that PmPV2 is a true enterotoxin, a role that has never been reported to lectins or perforin in animals. This extends by convergent evolution the presence of plant- and bacteria-like enterotoxins to animals, thus expanding the diversity of functions of MACPF proteins in nature.