Wojtaszek Malgorzata, Grzesiak Malgorzata, Pawlikowska Olga, Koziorowska Anna, Koziorowski Marek, Slomczynska Maria, Knapczyk-Stwora Katarzyna
Doctoral School of Exact and Natural Sciences, Jagiellonian University, Prof. St. Łojasiewicza 11 Street, Kraków, 30-348, Poland.
Department of Endocrinology, Institute of Zoology and Biomedical Research, Faculty of Biology, Jagiellonian University, Gronostajowa 9 Street, Kraków, 30-387, Poland.
Sci Rep. 2025 Jul 28;15(1):27386. doi: 10.1038/s41598-025-09895-y.
Endocrine-active compounds (EACs) derived from anthropogenic activities and bioactive components in maternal milk influence neonatal development, a critical period for postnatal uterine morphogenesis. Here, using an ex vivo model, we investigated whether neonatal exposure to the antiandrogen 2-hydroxyflutamide, the environmental estrogen 4-tert-octylphenol, and the organochlorine insecticide metabolite HPTE (which exhibits estrogenic, antiestrogenic, and/or antiandrogenic activity) induces oxidative stress and alters proliferation and apoptosis in uterine explants from 10-day-old piglets. Additionally, we assessed whether natural feeding provides protection against the adverse effects of EACs. We found that EACs disrupting androgen or estrogen signaling increased ROS/RNS production, enhanced specific antioxidant enzyme activity, and/or induced apoptosis exclusively in sow-fed piglets, suggesting a compensatory mechanism to maintain cellular homeostasis. Its absence in formula-fed piglets may indicate a reduced capacity to activate protective mechanisms against EACs, potentially due to delayed development. In contrast, EAC-induced alterations in uterine cell proliferation occurred in both feeding groups in a cell type- and feeding-dependent manner. These findings suggest that natural feeding does not fully protect against EAC-induced uterine development disruption, which may have long-term reproductive consequences. Moreover, they reinforce the notion that the neonatal period is a critical window of uterine development, highly sensitive to endocrine disruptors.
源自人为活动的内分泌活性化合物（EACs）以及母乳中的生物活性成分会影响新生儿发育，这是出生后子宫形态发生的关键时期。在此，我们使用体外模型研究了新生仔猪暴露于抗雄激素2-羟基氟他胺、环境雌激素4-叔辛基苯酚以及有机氯杀虫剂代谢物HPTE（其具有雌激素活性、抗雌激素活性和/或抗雄激素活性）是否会诱导氧化应激，并改变10日龄仔猪子宫外植体中的增殖和凋亡情况。此外，我们评估了自然喂养是否能提供保护，使其免受EACs的不利影响。我们发现，干扰雄激素或雌激素信号的EACs会增加活性氧/氮（ROS/RNS）的产生，增强特定抗氧化酶的活性，和/或仅在母乳喂养的仔猪中诱导凋亡，这表明存在一种维持细胞稳态的补偿机制。配方奶喂养的仔猪缺乏这种机制，这可能表明其激活针对EACs的保护机制的能力降低，可能是由于发育延迟所致。相比之下，EACs诱导的子宫细胞增殖变化在两个喂养组中均以细胞类型和喂养方式依赖的方式发生。这些发现表明，自然喂养并不能完全防止EACs对子宫发育的破坏，这可能会产生长期的生殖后果。此外，它们强化了这样一种观念，即新生儿期是子宫发育的关键窗口，对内分泌干扰物高度敏感。
