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

Pubertal mammary branching morphogenesis is a hormone-regulated process susceptible to exposure to chemicals with endocrine disruptive capacity, such as the UV-filter benzophenone-3 (BP3). Our aim was to assess whether intrauterine or in vitro exposure to BP3 modified the branching morphogenesis of the female mouse mammary gland. For this, pregnant mice 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 the mammary glands of the offspring were studied on postnatal day 45. Further, mammary organoids from untreated mice were cultured under branching induction conditions and exposed for 9 days to BP3 (1 × 10-6 M, 1 × 10-9 M, or 1 × 10-12 M with 0.01% ethanol as control) to evaluate the branching progression. Mice that were exposed to BP3 in utero showed decreased mRNA levels of progesterone receptor (PR) and WNT4. However, estradiol and progesterone serum levels, mammary histomorphology, proliferation, and protein expression of estrogen receptor alpha (ESR1) and PR were not significantly altered. Interestingly, direct exposure to BP3 in vitro also decreased the mRNA levels of PR, RANKL, and amphiregulin without affecting the branching progression. Most effects were found after exposure to 50 mg/kg/day or 1 × 10-6 M of BP3, both related to sunscreen application in humans. In conclusion, exposure to BP3 does not impair mammary branching morphogenesis in our models. However, BP3 affects PR transcriptional expression and its downstream mediators, suggesting that exposure to BP3 might affect other developmental stages of the mammary gland.

Collagen remodeling during cervical ripening is a key event for successful vaginal delivery

Parturition involves a complex interplay of maternal and fetal factors. An understanding of the physiological mechanisms involved in maternal adaptations would be of great benefit in the diagnosis, management, and outcome of dystocic parturition, an important problem in human health care and animal production. In tjis review, we consider the histofunctional changes in the uterine cervix that are essential for sucessful vaginal delivery and focus on work from our laboratory. The functions of the uterine cervix change considerably during pregnancy. As the uterus enlarges to accommodate the growing fetus, the cervix behaves essentially as a barrier. At term, however, the cervix softens and dilates through a process known as cervical ripening. This process is extremely complex and involves interactions between different cellular compartments and the extracellular matrix, as well as properly timed biochemical cascades, and stromal infiltration by inflammatory cells. Since the main component of the uterine cervix is connective tissue, collagen remodeling is a key event for ripening and delivery. Moreover, because of their intrinsic mechanical properties, elastic fibers may be involved in the recovery of shape immediately after parturition. Despite the advances in our knowledge of cervical ripening, the signals responsible for initiating these changes remain to be elucidated. By understanding the mechanisms involved in these changes, it should be possible to adress complex issues such as cervical incompetence, pre- and post-term delivery, and proper "ripening" of the cervix in order to avoid surgical delivery.