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

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

TOXICOLOGY AND APPLIED PHARMACOLOGY

ACADEMIC PRESS INC ELSEVIER SCIENCE

Año: 2024 vol. 484

0041-008X

Pubertal mammary branching morphogenesis is ahormone-regulated process susceptible to exposure to chemicals with endocrinedisruptive capacity, such as the UV-filter benzophenone-3 (BP3). Our aim was toassess whether intrauterine or in vitro exposure to BP3 modified thebranching morphogenesis of the female mouse mammary gland. For this, pregnantmice were dermally exposed to BP3 (0.15 or 50 mg/kg/day) from gestation day(GD) 8.5 to GD18.5. Sesame oil treatment served as control. Changes of themammary glands of the offspring were studied on postnatal day 45. Further, mammaryorganoids from untreated mice were cultured under branching inductionconditions and exposed for 9 days to BP3 (1×10-6 M, 1×10-9M, or 1×10-12 M with 0.01% ethanol as control) to evaluate thebranching progression. Mice that were exposed to BP3 in utero showeddecreased mRNA levels of progesterone receptor (PR) and WNT4. However, estradioland progesterone serum levels, mammary histomorphology, proliferation, andprotein expression of estrogen receptor alpha (ESR1) and PR were not significantlyaltered. Interestingly, direct exposure to BP3 in vitro also decreased the mRNA levels of PR, RANKL, and amphiregulinwithout affecting the branching progression. Most effects were found afterexposure to 50 mg/kg/day or 1×10-6 M of BP3, both related tosunscreen application in humans. In conclusion, exposure to BP3 does not impairmammary branching morphogenesis in our models. However, BP3 affects PR transcriptionalexpression and its downstream mediators, suggesting that exposure to BP3 mightaffect other developmental stages of the mammary gland.