TY - JOUR
T1 - Bugs on Drugs:
T2 - Paracetamol Exposure Reveals Genotype-Specific Generational Effects on Life History Traits in Drosophila melanogaster
AU - Hundebøl, Birk Nete Randlev Gleerup
AU - Rohde, Palle Duun
AU - Kristensen, Torsten Nygaard
AU - Jensen, Rune Wittendorff Mønster
AU - Vosegaard, Thomas
AU - Sørensen, Jesper Givskov
PY - 2024/10/1
Y1 - 2024/10/1
N2 - Few investigations have been made to determine whether pharmaceutical drugs cause any generational effects. These effects can be divided into intergenerational and transgenerational effects. In insects, the F1 offspring of exposed individuals are considered to show intergenerational effects (as they have been exposed as germ cells or early embryos), while the F2 generation is fully non-exposed and considered to show transgenerational effects. Here, the common over-the-counter (OTC) drug, paracetamol, is investigated for genotype-specific responses and effects across generations on three life-history traits: fecundity, longevity, and spontaneous locomotor activity levels in the model species Drosophila melanogaster. Seven isofemale D. melanogaster lines were exposed to a high and intermediate dose of paracetamol determined by a dose-response curve. NMR investigations verified the long-term presence of paracetamol in the food substrate. Phenotypic effects of paracetamol ingestion were investigated on flies exposed to the drug and in their offspring and grand-offspring. The dose-response curve indicated genotype-specific responses to paracetamol. In the following experiment, all traits investigated displayed significant effects of paracetamol ingestion for at least one of the seven isofemale lines, and we detected strong genotype-specific responses to paracetamol. Fecundity tended to increase in individuals directly exposed to the drug whereas fecundity in the F2 generation was reduced (transgenerational). Longevity generally decreased in directly exposed individuals but tended to increase in F1 offspring (intergenerational). Paracetamol effects on spontaneous locomotor activity were primarily detected as transgenerational effects and were rarely seen in directly exposed individuals. However, across lines, no clear overall trend could be determined for any trait. The generational effects and marked genotype-specific response to paracetamol warrants further investigation of both genotype-specific responses and generational effects in general.
AB - Few investigations have been made to determine whether pharmaceutical drugs cause any generational effects. These effects can be divided into intergenerational and transgenerational effects. In insects, the F1 offspring of exposed individuals are considered to show intergenerational effects (as they have been exposed as germ cells or early embryos), while the F2 generation is fully non-exposed and considered to show transgenerational effects. Here, the common over-the-counter (OTC) drug, paracetamol, is investigated for genotype-specific responses and effects across generations on three life-history traits: fecundity, longevity, and spontaneous locomotor activity levels in the model species Drosophila melanogaster. Seven isofemale D. melanogaster lines were exposed to a high and intermediate dose of paracetamol determined by a dose-response curve. NMR investigations verified the long-term presence of paracetamol in the food substrate. Phenotypic effects of paracetamol ingestion were investigated on flies exposed to the drug and in their offspring and grand-offspring. The dose-response curve indicated genotype-specific responses to paracetamol. In the following experiment, all traits investigated displayed significant effects of paracetamol ingestion for at least one of the seven isofemale lines, and we detected strong genotype-specific responses to paracetamol. Fecundity tended to increase in individuals directly exposed to the drug whereas fecundity in the F2 generation was reduced (transgenerational). Longevity generally decreased in directly exposed individuals but tended to increase in F1 offspring (intergenerational). Paracetamol effects on spontaneous locomotor activity were primarily detected as transgenerational effects and were rarely seen in directly exposed individuals. However, across lines, no clear overall trend could be determined for any trait. The generational effects and marked genotype-specific response to paracetamol warrants further investigation of both genotype-specific responses and generational effects in general.
KW - epigenetic inheritance
KW - fecundity
KW - genotype by environment
KW - insect model
KW - longevity
KW - personalized medicine
KW - pharmaceutical
KW - precision medicine
KW - spontaneous activity
UR - http://www.scopus.com/inward/record.url?scp=85207639051&partnerID=8YFLogxK
U2 - 10.3390/insects15100763
DO - 10.3390/insects15100763
M3 - Journal article
C2 - 39452339
SN - 2075-4450
VL - 15
JO - Insects
JF - Insects
IS - 10
M1 - 763
ER -