Abstract
Evidences suggest that maternal exposure to endocrine disruptor insecticide cypermethrin (CYP) affects the reproductive functions of offspring. However, its molecular effects are not well researched. This study elucidates the effects of CYP on gonadal steroidogenesis, gametogenesis and sperm epigenome of perinatally exposed F1 rat offspring. CYP (1, 10, 25 mg/kg bw/day) and Diethylestilbestrol (10 µg/kg bw/day; positive control) were gavaged once daily to pregnant dams from gestational day 6 to postnatal day 21 and their effects were assessed in F1 adults. Dysregulated steroidogenesis was observed in F1 testis; expression of Star, Cyp11a1 and Cyp19a1 were upregulated and Hsd3b1, Cyp17a1, Hsd17b3 downregulated. Expression of spermatogenesis cell-type markers Pcna, Plzf, Sohlh2 were upregulated and Ccna1, Sycp1, Ccnb1, Acrv, Amh downregulated. Upon epigenetic investigations of F1 spermatozoa; global hypermethylation, H19 DMR hypomethylation and increased expression of testicular Dnmts were observed. In F1 ovaries, expression of all studied steroidogenesis genes and oogenesis markers such as Amh, Gdf9, Ccnb1 and Pcna were altered. Amh was downregulated and Gdf9 was found to be upregulated. Overall, perinatal CYP exposure hampers molecular control of steroidogenesis and gametogenesis processes along with sperm epigenome in CYP exposed F1 offspring.
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