(113) PFOS caused fertility defects and disrupted spermatogenic gene networks in the male medaka with a transgenerational history of ancestral BPA exposure  

PFOS caused fertility defects and disrupted spermatogenic gene networks in the male medaka with a transgenerational history of ancestral BPA exposure  

Sourav Chakraborty¹; Ramji Kumar Bhandari¹

1. Biological sciences, University of Missouri, Columbia

Abstract Text:

PFOS caused fertility defects and disrupted spermatogenic gene networks in the male medaka with a transgenerational history of ancestral BPA exposure 

Sourav Chakraborty¹; Ramji Kumar Bhandari¹

1.Biological sciences, University of Missouri, Columbia

Environmental chemical exposure effects on reproduction are found to be heritable, suggesting that even when toxic chemicals are phased out, they may remain relevant due to the inter- or transgenerational inheritance of their adverse biological effects and exposure memories. How organisms will respond when they are exposed to contemporary environmental chemicals overlaid upon the transgenerational inheritance of their ancestors’ exposure profiles is currently unknown. In this study, we investigated the effects of a second hit of perfluorooctane sulfonate (PFOS) exposure on male reproductive health in medaka fish (Oryzias latipes) with or without a history of ancestral bisphenol A (BPA) exposure. The PFOS exposure occurred in offspring four generations after ancestors’ BPA exposure (10 µg/L) during their embryonic development. Three concentrations of PFOS (0, 0.002, and 0.02 mg/L for 21 days) were tested in two lineages: control lineage with no ancestral history of BPA exposure and BPA lineage whose ancestors were exposed to BPA four generations ago. Our results show that the second hit of PFOS significantly decreases fertility in the fish with the pre-existing history of ancestral BPA exposure. RNA sequencing of the testis revealed that PFOS exposure in the BPA lineage caused a significant increase in the numbers of upregulated genes. In contrast, in the control lineage, PFOS exposure led to an increase in the number of downregulated genes, particularly those related to cell cycle dysregulation in the testes. Differentially expressed genes in the PFOS exposed BPA lineage fish were unique, with the pathway enrichment related to apoptosis, proteolysis, and cytoskeletal disarrangement. The genes associated with Sertoli cell function and spermatogenesis, mainly associated with locomotion, mitotic cycle, and cell morphogenesis and were significantly dysregulated in the BPA lineage fish. Altogether, the present study found exacerbated fertility defects and significant alterations in the molecular networks associated with Sertoli cell function & spermatogenesis due to the second hit of PFOS in the fish with a history of ancestral BPA exposure, suggesting that a pre-existing history of ancestral environmental chemical exposure can be a contributing factor for adverse health outcomes in the upcoming generations upon exposure to contemporary legacy chemicals.