Paternal starvation affects metabolic gene expression during zebrafish offspring development and lifelong fitness

Dietary restriction in the form of fasting is a putative key to a healthier and longer life, but these benefits may come at a trade‐off with reproductive fitness and may affect the following generation(s). The potential inter‐ and transgenerational effects of long‐term fasting and starvation are particularly poorly understood in vertebrates when they originate from the paternal line. We utilised the externally fertilising zebrafish amenable to a split‐egg clutch design to explore the male‐specific effects of fasting/starvation on fertility and fitness of offspring independently of maternal contribution. Eighteen days of fasting resulted in reduced fertility in exposed males. While average offspring survival was not affected, we detected increased larval growth rate in F1 offspring from starved males and more malformed embryos at 24 h post‐fertilisation in F2 offspring produced by F1 offspring from starved males. Comparing the transcriptomes of F1 embryos sired by starved and fed fathers revealed robust and reproducible increased expression of muscle composition genes but lower expression of lipid metabolism and lysosome genes in embryos from starved fathers. A large proportion of these genes showed enrichment in the yolk syncytial layer suggesting gene regulatory responses associated with metabolism of nutrients through paternal effects on extra‐embryonic tissues which are loaded with maternal factors. We compared the embryo transcriptomes to published adult transcriptome datasets and found comparable repressive effects of starvation on metabolism‐associated genes. These similarities suggest a physiologically relevant, directed and potentially adaptive response transmitted by the father, independently from the offspring's nutritional state, which was defined by the mother.