Medroxyprogesterone acetate affects eye growth and the transcription of associated genes in zebrafish

Medroxyprogesterone acetate (MPA) is a widely used synthetic progestin in contraception pills and hormone replacement therapy. However, its effects on eye growth and development and function were largely unknown. In this study, the transcription of genes in the Notch signaling pathway and the visual cycle network were evaluated after chronic MPA exposure at 4.32 (L), 42.0 (M), and 424 (H) ng L^-1 for 120 days in zebrafish. Meanwhile, the histology of the eyes was also examined. Transcriptional results showed that MPA at all three concentrations significantly increased the transcription of notch1a, dll4, jag1a, ctbp1 and rbpjb (key genes in the Notch signaling pathway) in the eyes of females. The up-regulation of noth1a, ctbp1 and kat2b was also observed in the eyes of males exposed to MPA at 424 ng L^-1. In the visual cycle pathway, MPA increased the transcription of opn1sw1, opn1sw2, arr3a and rpe65a in the eyes of females from the M and H treatments. Histopathological analysis showed that exposure to 42.0 ng L^-1 of MPA increased the thicknesses of inner nuclear layer in females and outer segment in males. Moreover, exposure to 424 ng L^-1 of MPA increased the lens diameter in females. These results indicated that chronic MPA exposure affected the transcription of genes in the Notch signaling and in the visual cycle pathways, resulting in overgrowth of the eyes and interference of the eye functions. This study suggests that MPA pose a risk to fitness and survival of zebrafish in areas where MPA contamination exists.