FISH REPRODUCTION - EXACTLY WHO IS IN CONTROL?

The conventional wisdom is that reproduction is controlled by the brain-pituitary-gonadal (BPG) axis. A series of brain peptides, including kisspeptins, GnRHs and GnIHs regulate the synthesis and release of the gonadotropins - luteinizing hormone (LH) and follicle stimulating hormone (FSH) from the pituitary. LH and FSH, in turn, regulate steroidogenesis in the gonads, which drives spermatogenesis in the males and oogenesis in the females. However, recent advances in gene editing and functional genomics, using zebrafish as a model, demonstrate that this dogma may prove to be too simplistic. Silencing of several of the main hormones along the BP axis using TALEN and CRISPR knockout technologies, which completely eliminate the expression of the peptides/proteins throughout the full life span of the fish and is hereditary, does not always lead to loss of reproduction. In all cases, fish that do not express key hormones such as the two kisspeptins and their receptors, the two GnRHs, LH and FSH continue to display different degrees of reproduction, including full gametogenesis (with the exception of LH knockout fish, which do not undergo final oocyte maturation and ovulation) leading to the production of functional gametes, viable embryos, and phenotypically normal offspring that carry the gene mutations into the next generation and continue to reproduce. These findings are quite confusing to fish reproductive biologists and challenge the simple BPG concept. Interestingly, using laser ablation to entirely remove the soma and neurons of the reproductively most relevant GnRH3 during early development does lead to the arrest of gametogenesis and to sterile fish. Contrary to the finding in the brain and the pituitary, silencing of certain reproductive genes in early germ cells leads to a total lack of gametogenesis and sterile fish. Taken together, these findings demonstrate that fish can continue to reproduce despite the total absence of key reproductive hormones in the brain and the pituitary. This data further suggests that fish have developed back-up strategies and redundancies in which yet-to-be-discovered hormones and mechanisms compensate for the absence of the known reproductive regulators, thereby ensuring the continuation of reproduction and survival of the species. This new understanding has important implications for controlling fertility and sterility in aquaculture, which will be discussed.