TCER-1 promotes reproductive health in normal, fertile worms and metabolic homeostasis and longevity in germline-less animals.
A-C.tcer-1 mutants exhibit multiple fertility defects. Reproductive fitness parameters compared between wild type (N2, gray), daf-16 (red) and tcer-1 (orange) mutants, including fecundity (number of eggs laid, A), viability (percent of laid eggs that hatch successfully, B), oocyte production (C) grown at 20°C. tcer-1, but not daf-16, mutants are defective in all aspects and these phenotypes are aggravated further at 25°C (S4C Fig). D-F.tcer-1 mutants make defective sperm and oocytes. Functionality of tcer-1 mutants’ sperm and oocytes was assessed by crossing tcer-1 males to wild-type (N2) hermaphrodites (vertical striped bars) and tcer-1 hermaphrodites to N2 males (diagonal striped bars), respectively. Reproductive health measures were compared against control N2 hermaphrodites and males crossed to each other (gray bars). Shown here are results for fecundity (D) viability of eggs (E) and oocyte production (F). G, H.tcer-1 mutants exhibit inadequate germ-cell development and germline heterochrony. DAPI stained germline of wild type (N2) day 1 adults germ cell nuclei organized in spatial-temporal gradient, whereas, gonads from tcer-1 mutants exhibit significantly reduced germ-cell number. Gonads are outlined with yellow, dotted lines and scale bar in both images is 20μM. Germline heterochrony in the mutants is revealed by the presence of sperm (green arrows) within the proliferating region of the gonad and not within the spermatheca (demarcated with a green dotted line) as seen in N2. Quantification of germline defects is shown in S4 Fig. In A-F, asterisks represent the statistical significance of differences observed in an unpaired, two-tailed t-test with P values 0.05 (*), 0.005 (**) or < 0.0005 (***) between N2 and tcer-1 (orange asterisks) or daf-16 (red asterisks). I-K. Schematic representation of the model proposed based on the findings of this study. Our results suggest mechanisms by which DAF-16 and TCER-1 help maintain metabolic homeostasis in response to changes in the reproductive status of the animal (I). In fertile animals, TCER-1 ensures reproductive fitness, likely by promoting germ-cell proliferation and successful sperm-to-oocyte production switch in synchrony with somatic development (J). When the germline is lost, as in the case of glp-1 mutants, TCER-1 undergoes a role-reversal and inhibits the somatic program of reproduction instead (K). TCER-1 also represses anti-longevity genes independently. DAF-16, on the other hand restrains translation by repressing ribosomal-gene expression (K). Additionally, DAF-16 and TCER-1 enhance the expression of genes involved in both lipid-anabolic and lipid-catabolic pathways (depicted in K) in adaptation to germline depletion. We posit that the simultaneous enhancement of these ostensibly antagonistic processes (a) allows the animal to retain metabolic homeostasis during the physiological flux caused by germline loss, and (b) enables the production of lipid signaling moieties and/or ligands for transcription factors whose activities ultimately advance longevity.