Branching morphogenesis of the mouse mammary gland after exposure to benzophenone-3

SCHIERANO-MAROTTI, GONZALO; ALTAMIRANO, GABRIELA A.; ODDI, SOFÍA; GOMEZ, AYELEN L.; MEYER NICOLE; MUÑOZ-DE-TORO, MÓNICA; ZENCLUSSEN, ANA CLAUDIA; RODRIGUEZ, HORACIO A.; KASS, LAURA

TOXICOLOGY AND APPLIED PHARMACOLOGY

ACADEMIC PRESS INC ELSEVIER SCIENCE

Lugar: Amsterdam; Año: 2023

0041-008X

Pubertal mammary branching morphogenesis is a hormone-regulated processsusceptible to exposure to chemicals with endocrine disruptive capacity, such as theUV-filter benzophenone-3 (BP3). Our aim was to assess whether intrauterine or in vitroexposure to BP3 modified the branching morphogenesis of the female mousemammary gland. For this, pregnant mice were dermally exposed to BP3 (0.15 or 50mg/kg/day) from gestation day (GD) 8.5 to GD18.5. Sesame oil treatment served ascontrol. Changes of the mammary glands of the offspring were studied on postnatalday 45. Further, mammary organoids from untreated mice were cultured underbranching induction conditions and exposed for 9 days to BP3 (1×10-6 M, 1×10-9 M, or1×10-12 M with 0.01% ethanol as control) to evaluate the branching progression. Micethat were exposed to BP3 in utero showed decreased mRNA levels of progesteronereceptor (PR) and WNT4. However, estradiol and progesterone serum levels,mammary histomorphology, proliferation, and protein expression of estrogen receptoralpha (ESR1) and PR were not significantly altered. Interestingly, direct exposure toBP3 in vitro also decreased the mRNA levels of PR, RANKL, and amphiregulin withoutaffecting the branching progression. Most effects were found after exposure to 50mg/kg/day or 1×10-6 M of BP3, both related to sunscreen application in humans. Inconclusion, exposure to BP3 does not impair mammary branching morphogenesis inour models. However, BP3 affects PR transcriptional expression and its downstreammediators, suggesting that exposure to BP3 might affect other developmental stages ofthe mammary gland.