title: Identification of Drosophila-based endpoints for the assessment and understanding of xenobiotic-mediated male reproductive adversities.
abstract: Men are at risk of becoming completely infertile due to innumerable environmental chemicals and pollutants. These xenobiotics, hence, should be tested for their potential adverse effects on male fertility. However, the testing load, a monumental challenge for employing conventional animal models, compels the pursuit of alternative models. Towards this direction, we show here that Drosophila melanogaster, an invertebrate, with its well characterized/conserved male reproductive processes/proteome, recapitulates male reproductive toxicity phenotypes observed in mammals when exposed to a known reproductive toxicant, dibutyl phthalate (DBP). Analogous to mammals, exposure to DBP reduced fertility, sperm counts, seminal proteins, increased oxidative modification/damage in reproductive tract proteins and altered the activity of a hormone receptor (estrogen related receptor) in Drosophila males. In addition, we show here that DBP is metabolized to monobutyl phthalate (MBP) in exposed Drosophila males and that MBP is more toxic than DBP, as observed in higher organisms. These findings suggest Drosophila as a potential alternative to traditional animal models for the prescreening of chemicals for their reproductive adversities and also to gain mechanistic insights into chemical-mediated endocrine disruption and male infertility.
authors: Embryotoxicology, CSIR-Indian Institute of Toxicology Research, Mahatma Gandhi Marg, Lucknow 226001, UP, India Academy of Scientific and Innovative Research (AcSIR), Lucknow 226001, UP, India.
authors: Snigdha
authors: S
authors: Misra
authors: Embryotoxicology, CSIR-Indian Institute of Toxicology Research, Mahatma Gandhi Marg, Lucknow 226001, UP, India.
authors: Anshuman
authors: A
authors: Singh
authors: Analytical Chemistry, CSIR-Indian Institute of Toxicology Research, Mahatma Gandhi Marg, Lucknow 226001, UP, India Academy of Scientific and Innovative Research (AcSIR), Lucknow 226001, UP, India.
authors: Ratnasekhar
authors: R
authors: C H
authors: Embryotoxicology, CSIR-Indian Institute of Toxicology Research, Mahatma Gandhi Marg, Lucknow 226001, UP, India Academy of Scientific and Innovative Research (AcSIR), Lucknow 226001, UP, India.
authors: Vandana
authors: V
authors: Sharma
authors: Analytical Chemistry, CSIR-Indian Institute of Toxicology Research, Mahatma Gandhi Marg, Lucknow 226001, UP, India Academy of Scientific and Innovative Research (AcSIR), Lucknow 226001, UP, India.
authors: Mohana Krishna
authors: MK
authors: Reddy Mudiam
authors: Embryotoxicology, CSIR-Indian Institute of Toxicology Research, Mahatma Gandhi Marg, Lucknow 226001, UP, India Academy of Scientific and Innovative Research (AcSIR), Lucknow 226001, UP, India raviram@iitr.res.in.
authors: Kristipati Ravi
authors: KR
authors: Ram
mesh_terms: D000818:Animals; D003993:Dibutyl Phthalate / Q000493:pharmacokinetics / Q000633:toxicity*; D004331:Drosophila melanogaster / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D004785:Environmental Pollutants / Q000493:pharmacokinetics / Q000633:toxicity*; D005298:Fertility / Q000187:drug effects / Q000235:genetics; D007248:Infertility, Male / Q000139:chemically induced* / Q000235:genetics / Q000473:pathology; D008297:Male; D018613:Microscopy, Confocal; D010795:Phthalic Acids / Q000493:pharmacokinetics / Q000633:toxicity*; D012098:Reproduction / Q000187:drug effects / Q000235:genetics; D013076:Sperm Count; D013094:Spermatozoa / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D059467:Transcriptome / Q000187:drug effects; D015262:Xenobiotics / Q000493:pharmacokinetics / Q000633:toxicity*
chemical_list: D004785:Environmental Pollutants; D010795:Phthalic Acids; D015262:Xenobiotics; D003993:Dibutyl Phthalate; C028577:monobutyl phthalate
keywords: Drosophila; endocrine disruption; estrogen related receptor; male infertility; phthalate