Identification of the estrogen receptor subtypes associated with testis-ova induction in the medaka

Exposure to estrogenic endocrine disrupting chemicals (EDCs) poses a significant threat to aquatic wildlife. They are known to induce a range of adverse reproductive and developmental disorders that include induction of oocytes in the testis (testis-ova), however, mechanisms underlying the testis-ova induction are not fully understood. In this study, applying the use of estrogen receptor (esr) 1, esr2a and esr2b knock out (KO) in medaka exposed to 17β-estradiol (E2), we investigated which Esr subtypes mediate testis-ova formation. Loss of any esr subtype did not affect gonadal differentiation. Upon estrogen exposure, testis-ova was not induced in either esr1 or esr2a KO testes, whereas some esr2b KO male medaka developed testis-ova. These results illustrate that both esr1 and esr2a have essential roles in testis-ova formation, while esr2b likely plays a partial, but non-essential, roles on this process. Expressions of genes associated with testis-ova, such as zpc5, 42sp50, and figa showed no significant increase upon E2 exposure in all esr KO medaka testes. We thus provide evidence for different functionalization of Esr subtypes in vivo regarding endocrine disrupting effects. Our findings contribute to understanding the molecular initiating events of adverse effects induced by estrogenic EDCs.