Atrazine or bisphenol A mediated negative modulation of mismatch repair gene, mlh1 leads to defective oogenesis and reduced female fertility in Drosophila melanogaster

The study reports the effects of an herbicide (atrazine) and a plasticizer (Bisphenol A, BPA) on the transcriptional modulation of a mismatch repair gene (mlh1) and its adverse consequences on female fertility using Drosophila as a model. Through a chemical screen, we show that exposure to atrazine or BPA significantly downregulates mlh1 and the exposed flies had reduced fertility with smaller ovaries having reduced number of mature oocytes and abnormal distribution of ovarian follicles with increased apoptosis in them. These females had increased double-strand breaks as well as reduced synaptonemal complex formation in their ovaries suggesting altered meiotic crossing over. The eggs of these females were defective in their maternal transcripts as well as proteins and consequently, after fertilization, these eggs exhibited abnormal embryonic development. Interestingly, these phenotypes parallel that of mlh1 mutants. Further, exposure of females having reduced Mlh1 levels (mlh1(e00130)/CyO) to atrazine or BPA caused severe defective phenotypes at a higher proportion than normal flies. Our findings reveal the critical role of mlh1 in atrazine and BPA mediated female reproductive toxicity, and opens up a possibility of toxicants affecting female fertility by modulating the MMR genes. (C) 2019 Elsevier Ltd. All rights reserved.