Underlying Physiological Mechanisms Controlling the Reproductive Axis of Rabbit Does

An increasing body of evidence unequivocally points to a strict inter-link between nutrition and reproduction. The paradigmatic case of leptin is examined to uncover nutritional-related physiological, cellular and molecular mechanisms. The presence of leptin receptors (Ob-R) in the ovary, oviduct, hypothalamus and anterior pituitary suggests that leptin is involved in a large array of regulatory actions at different levels of the hypothalamus-pituitary-ovary (HPO) axis of the rabbit. In luteal tissue, leptin increases prostaglandin (PG) F2α synthesis but inhibits progesterone release using, respectively, the JAK/STAT and MAPK pathways. In the oviducts, leptin inhibits PGF2α, but stimulates PGE2 synthesis. A nutritional challenge, evoked by 48-h fasting before AI, depresses all the reproductive parameters, reduces estradiol-17β pulse frequency and amplitude, lowers LH peak surge following GnRH injection, down-regulates the expression of oestrogen receptors (ER) in anterior pituitary, and causes a fall in plasma leptin concentrations. Although leptin secretion seems to be regulated by caloric intake rather than by adipose mass, taken together these findings support that leptin may act as a metabolic signal to switch on or off reproductive activity. Stress-related mechanisms are briefly discussed from the perspective of the potential benefit derived by modulating the neuroendocrine as well as the immune system during early development. Regarding the luteal function, several different luteolytic and luteotrophic forces at work as well as many levels at which these opposing and balancing influences may exert, via paracrine and/or autocrine mechanisms, their action in the corpus luteum (CL). The emerging role of the nitric oxide (NO)/NO synthase (NOS) system in the regulation of rabbit CL function is presented. Both endothelial and inducible isoforms of NOS are expressed at gene and protein levels in the CL, eNOS being regulated during pseudopregnancy. PGE2 exerts its luteotrophic effect through NOS down-regulation, while the PGF2α luteolytic effect is mediated by NOS up -regulation both in vitro and in vivo. During luteolysis, luteal cytokines may be involved in the up-regulation of NOS activity, while downstream NO may inhibit steroidogenesis and induce, after removal of the protective action of progesterone, the expression of p53 gene, a transcriptional regulator of apoptotic genes. First evidence for the action of endothelin–1 (ET-1), a potent vasoconstrictor synthesized by vascular endothelium, in promoting the luteolytic cascade mechanism in rabbits is enlightened.