title: Detection of transgenerational spermatogenic inheritance of adult male acquired CNS gene expression characteristics using a Drosophila systems model.
abstract: Available instances of inheritance of epigenetic transgenerational phenotype are limited to environmental exposures during embryonic and adult gonadal development. Adult exposures can also affect gametogenesis and thereby potentially result in reprogramming of the germline. Although examples of epigenetic effects on gametogenesis exist, it is notable that transgenerational inheritance of environment-induced adult phenotype has not yet been reported. Epigenetic codes are considered to be critical in neural plasticity. A Drosophila systems model of pentylenetetrazole (PTZ) induced long-term brain plasticity has recently been described. In this model, chronic PTZ treatment of adult males causes alterations in CNS transcriptome. Here, we describe our search for transgenerational spermatogenic inheritance of PTZ induced gene expression phenotype acquired by adult Drosophila males. We generated CNS transcriptomic profiles of F(1) adults after treating F(0) adult males with PTZ and of F(2) adults resulting from a cross between F(1) males and normal females. Surprisingly, microarray clustering showed F(1) male profile as closest to F(1) female and F(0) male profile closest to F(2) male. Differentially expressed genes in F(1) males, F(1) females and F(2) males showed significant overlap with those caused by PTZ. Interestingly, microarray evidence also led to the identification of upregulated rRNA in F(2) males. Next, we generated microarray expression profiles of adult testis from F(0) and F(1) males. Further surprising, clustering of CNS and testis profiles and matching of differentially expressed genes in them provided evidence of a spermatogenic mechanism in the transgenerational effect observed. To our knowledge, we report for the first time detection of transgenerational spermatogenic inheritance of adult acquired somatic gene expression characteristic. The Drosophila systems model offers an excellent opportunity to understand the epigenetic mechanisms underlying the phenomenon. The finding that adult acquired transcriptomic alteration in soma is spermatogenically inherited across generations has potential implications in human health and evolution.
authors.affiliation: Institute of Genomics and Integrative Biology, Council of Scientific and Industrial Research, Delhi, India. abhaysharma@igib.res.in
authors.forename: Abhay
authors.initials: A
authors.lastname: Sharma
authors.forename: Priyanka
authors.initials: P
authors.lastname: Singh
mesh_terms: D000818:Animals; D002490:Central Nervous System / Q000187:drug effects* / Q000196:embryology; D016000:Cluster Analysis; D015331:Cohort Studies; D003433:Crosses, Genetic; D004331:Drosophila melanogaster; D044127:Epigenesis, Genetic; D005260:Female; D006801:Humans; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D010433:Pentylenetetrazole / Q000494:pharmacology; D017422:Sequence Analysis, DNA; D013091:Spermatogenesis; D013737:Testis / Q000378:metabolism
chemical_list: D010433:Pentylenetetrazole