Reproduction potentiated in nematodes (Caenorhabditis elegans) and guppy fish (Poecilia reticulata) by adding a synthetic peptide to their aqueous environment

Abstract

Ambient exposure to a short synthetic peptide has enhanced fecundity (number of offspring) in invertebrates and vertebrates, ostensibly by disinhibiting reproduction. In separate experiments, nematodes (Caenorhabditis elegans) and guppy fish (Poecilia reticulata) were exposed via their aqueous environment to a dissolved synthetic hexamer (6mer) peptide, IEPVFT (EPL036), at a concentration of. In the case of the worms, peptide was added to their aqueous buffer daily throughout the experiment (14 days); for the guppies, peptide administration was on the first 15 alternate days in a 50 week experiment. Fecundity rose by 79% among the worms. The number of descendants of the treated guppies was more than four times that of controls by week 26 (103 versus 25, including 72 juveniles versus 6), with 15.4% more estimated biomass in the test tank in total (i.e. including founders). It was deduced that treated females bred earlier, at a smaller size, and had larger brood sizes. The total number of fish in the control tank had caught up by termination, but biomass continued to lag the test tank. There were no overt signs of toxicity among either the worms or the fish. Bioinformatics has been unilluminating in explaining these results in terms, for example, of mimicry of an endogenous regulator. A mass spectrometric campaign to identify a receptor, using murine brain for expediency, proved inconclusive. Molecular modelling in silico indicated unexpectedly that the hexamer EPL036 might be acting as an antagonist, to pro-fecundity effect; that is, as a blocker of an inhibitor. This suggests that there awaits discovery an evolutionarily conserved reproductive inhibitor and its (anti-fecundity) receptor.

Mysterious inhibitory cell regulator investigated and found likely to be secretogranin II related

“…The low salt/high salt 7–8 kDa forms determined in anionic exchange chromatography fractions by western blotting could be accounted for by differential charge distribution of the kind seen in SgII and particularly associated with amphipathic helices and sorting domains ( Courel et al, 2008 ). A receptor identification study using EPL001 involved mouse brain ( Davies et al, 2015 ). No conventional receptors were identified.…”

“…The 14 aa sequence also proved resistant to multiple attempts at molecular biological elucidation, based on probing DNA and RNA libraries. Molecular modelling coupled with quantitative structure activity relationship (QSAR) analysis, as used previously ( Davies et al, 2015 ), pointed to EPL001’s C -terminal FNNI as a potentially key binding site, representing a lipophilic/hydrophobic cleft. An anti-EPL001 antibody targeted at the C -terminal end of the peptide has accordingly been deployed here in an attempt to purify molecular species that bound to the antibody in material from the rat and sheep and, for a cross-phylum comparison, the fruit fly D. melanogaster .…”

Hexapeptides from a mammalian inhibitory hormone activate and inactivate nematode reproduction

“…In line with the latter observation, EPL030's Front 6, EPL630, is anti-fecundity in S. siamkayai, while as yet untried in C. elegans. Meanwhile, the grandparental EPL001 14mer in C. elegans is pro-fecundity (Davies & Hart, 2008;Davies et al, 2015). How is all this to be untangled?…”

“…The lock is possibly a granin-style non-canonical receptor, representing a novel protein target for drug development. EPL001 has been deployed in mammalian binding studies to inconclusive effect (Davies et al, 2015). The use of the more reliably active EPL120 and EPL601 can be suggested as the next step in the research, to snare the receptor and enable its deployment to trap the endogenous ligand.…”

“…The attempt was made here to replicate prior fecundity work (Davies & Hart, 2008;Davies et al, 2015) in another species of nematode, the entomopathogenic (insect slaying) Steinernema siamkayai Stock, Somsook & Reid 1998. Species confirmation involved standard morphological and molecular techniques (S3, Nematodes).…”