Abstract:
Bisphenol A (BPA) is a highly pervasive chemical in consumer products with its ascribed endocrinedisrupting properties. Several studies have shown the cytotoxic, genotoxic, and carcinogenic property
of BPA over a multitude of tissues. Although BPA exposure has earlier been implicated in female infertility, the underlying molecular mechanisms explaining the toxicity of BPA in the ovary remains less
understood. In the present study, a plausible correlation between redox balance or inflammatory
signaling and reproductive fitness upon BPA exposure has been examined in zebrafish (Danio rerio)
ovary. Congruent with significant alteration of major antioxidant enzymes (SOD1, SOD2, catalase, GPx1a,
GSTa1) at the transcript level, 30 d BPA exposure at environmentally relevant concentrations (1, 10 and
100 mg L 1
) promotes ovarian ROS/RNS synthesis, lipid peroxidation but attenuates catalase activity
indicating elevated stress response. BPA promotes a sharp increase in ovarian p38 MAPK, NF-kB phosphorylation (activation), inducible nitric oxide synthase (Nos2a), and pro-inflammatory cytokines (TNF-a
and IL-1b) expression, the reliable markers for inflammatory response. Congruent to an increased
number of atretic follicles, BPA-exposed zebrafish ovary reveals elevated Bax/Bcl2 ratio, activation of
caspase-8, -3 and DNA breakdown suggesting heightened cell death. Importantly, significant alteration in
nuclear estrogen receptor (ER) transcripts (esr1, esr2a, and esr2b) and proteins (ERa, ERb), gonadotropin
receptors, and markers associated with steroidogenesis and growth factor gene expression in BPAexposed ovary correlates well with impaired ovarian functions and maturational response. Collectively, elevated oxidative/nitrosative stress-mediated inflammatory response and altered ER expression
can influence ovarian health and reproductive fitness in organisms exposed to BPA environment.
