Optimizing fecundity in Caenorhabditis elegans necessitates tuning the allocation of nutrients to growth, longevity, and progeny production. Thus, it is often proposed that these traits are mutually exclusive under optimized conditions. Accordingly, crosstalk between the germline and soma in lifespan regulation has been extensively studied. In a screen for modifiers of NHR-49 activities, we identified two proteins that impact progeny production: the nuclear hormone receptor NHR-88 and the cytochrome P450 CYP-35A5. Initial mutant characterization showed that
nhr-88(
tm1033) does not affect progeny production, while the cyp-35a5
(ok1985) allele decreases total brood. Analysis of the germline in cyp-35a5 mutants revealed a reduction in the number of germ cells and a shortened mitotic region. Surprisingly, a strain carrying mutations in both
nhr-88 and cyp-35a5 not only rescued the brood size defect of the cyp-35a5 single mutant, but increased progeny production to 35% over that of wildtype. This dramatic effect on fecundity is seen despite incomplete rescue of germline phenotypes. Interestingly, the role of the
nhr-88 mutation in increasing brood size in a cyp-35a5 background is temperature-sensitive, showing an increase only at moderate growth temperatures.
Consistent with the idea of an inverse correlation between fecundity and longevity, we see that the reduced germline in cyp-35a5 mutants corresponds to a 17% increase in mean lifespan. However, the
nhr-88;cyp-35a5 double mutant shows a modest increase in lifespan while also increasing brood size, suggesting that the number of mitotic germ cells may have a stronger effect on longevity than the number of progeny produced. We propose that these genes act together to affect brood production by altering proliferation in the germline via a shift in the mitosis-to-meiosis transition zone. Additionally, cyp-35a5 animals contain high levels of several polyunsaturated fatty acids, many of which have been shown to affect germ cell proliferation or brood size. Our data are consistent with a model in which CYP-35A5 negatively regulates NHR-88 to delay exit from mitosis, possibly by destroying an NHR-88 agonist. Further studies are underway to determine whether the NHR-88-dependent impact of CYP-35A5 on the germline is mediated by these fatty acid species.