Abstract
Declining germline quality is a major cause of reproductive senescence. Potential remedies could be found by studying regulatory pathways that promote germline quality. Several lines of evidence, including a C. elegans male pheromone ascr#10 that counteracts the effects of germline aging in hermaphrodites, suggest that the nervous system plays an important role in regulating germline quality. Inspired by the fact that serotonin mediates ascr#10 signaling, here we show that serotonin reuptake inhibitors recapitulate the effects of ascr#10 on the germline and promote healthy oocyte aging in C. elegans. Surprisingly, we found that pharmacological increase of serotonin signaling stimulates several developmental processes in D. melanogaster, including improved oocyte quality, although underlying mechanisms appear to be different between worms and flies. Our results reveal a plausibly conserved role for serotonin in maintaining germline quality and identify a class of therapeutic interventions using available compounds that could efficiently forestall reproductive aging.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 24-30 |
| Number of pages | 7 |
| Journal | Developmental Biology |
| Volume | 499 |
| DOIs | |
| State | Published - Jul 2023 |
Funding
We thank Rick Morimoto for generous hospitality and Bob Holmgren for flies. This work was funded in part by an NIH ( R01GM126125 ) grant to IR. We thank WormBase and the Caenorhabditis Genetics Center (CGC ). WormBase is supported by grant U41 HG002223 from the National Human Genome Research Institute at the NIH , the UK Medical Research Council , and the UK Biotechnology and Biological Sciences Research Council . The CGC is funded by the NIH Office of Research Infrastructure Programs ( P40 OD010440 ).
Keywords
- C. elegans
- D. melanogaster
- Germline
- SSRIs
- Serotonin
ASJC Scopus subject areas
- Molecular Biology
- Developmental Biology
- Cell Biology