In utero exposure to bisphenol-A disrupts key elements of retinoid system in male mice offspring

Area of Science:

• Endocrinology
• Toxicology
• Developmental Biology

Background:

• The retinoid system regulates critical cellular functions like mitosis and differentiation.
• Endocrine disrupting chemicals (EDCs) can interfere with retinoid signaling.
• Data on bisphenol-A's (BPA) developmental impact on the hepatic retinoid system is limited.

Purpose of the Study:

• To investigate the effects of in utero bisphenol-A (BPA) exposure on the developing hepatic retinoid system in male mice.
• To assess changes in retinoid concentrations and gene expression related to retinoid metabolism and signaling pathways.

Main Methods:

• Male mice were exposed to varying doses of BPA (0, 10, 100 μg/kg bw/day) via maternal subcutaneous injection from gestational day 9-16.
• Liver tissues were collected at postnatal day 30 for analysis of retinoid concentrations and gene expression.
• Key genes involved in retinoid biosynthesis, transport, and signaling were quantified.

Main Results:

• BPA exposure increased all-trans-retinoic acid concentration and the expression of genes involved in its biosynthesis (Adh1, Aox1, Cyp1a2).
• BPA altered retinoid transport by reducing hepatocyte efflux (Mrp3) and increasing biliary excretion (Bcrp).
• Retinoid signaling was disrupted, evidenced by reduced expression of Rxrβ and increased Fgf21, with associations found between specific receptor expressions and all-trans-retinoic acid levels.

Conclusions:

• In utero BPA exposure significantly disrupts the hepatic retinoid system in male mice.
• These disruptions are linked to altered glucose metabolism and pancreatic function in adulthood.
• Findings highlight BPA's potential as an EDC affecting retinoid signaling and metabolic health.