Neuroscience Program, University of Illinois at Urbana-Champaign, 603 E. Daniel Street, Champaign, IL, 61820, United States.
Department of Psychology, Bowling Green State University, 822 E Merry Ave, Bowling Green, OH, 43403, United States.
Neurotoxicology. 2021 Dec;87:167-173. doi: 10.1016/j.neuro.2021.09.007. Epub 2021 Sep 29.
Phthalates are a class of endocrine disruptors found in a variety of consumer goods, and offspring can be exposed to these compounds during gestation and lactation. Our laboratory has found that perinatal exposure to an environmentally relevant mixture of phthalates resulted in a decrease in cognitive flexibility and in neuron number in the adult rat medial prefrontal cortex (mPFC). Here, we examine effects of phthalate treatment on prenatal cellular proliferation and perinatal apoptosis in the mPFC. To examine the phthalate effects on cellular proliferation, dams consumed 0, 1, or 5 mg/kg of the phthalate mixture daily from embryonic day 2 (E2) through the day of birth (P0), and on E16 and E17, they were injected with BrdU. The mPFC of offspring was analyzed on P5 and showed a decrease in labelled cells in the phthalate exposed groups. To examine whether changes in BrdU density observed on P5 were due to altered cell survival, cell death was measured on E18, P0, and P5 using a TUNEL assay in a separate cohort of prenatally exposed offspring. There was an increase in TUNEL labelled cells at E18 in the phthalate exposed groups. In the final experiment, dams consumed the phthalate mixture from E2 through P10, at which time mPFC tissue was stained with TUNEL. Phthalate treated subjects showed a higher density of apoptotic cells at P10. These results indicate both pre- and postnatal phthalate exposure increases apoptosis in the male and female rat mPFC. While the impact of phthalates on proliferation cannot be ruled out, these data do not allow for definitive conclusions.
邻苯二甲酸酯是一类存在于各种消费品中的内分泌干扰物，后代在妊娠和哺乳期可能会接触到这些化合物。我们的实验室发现，围产期暴露于环境相关的邻苯二甲酸酯混合物会导致成年大鼠前额皮质（mPFC）中的认知灵活性和神经元数量下降。在这里，我们研究了邻苯二甲酸酯处理对 mPFC 产前细胞增殖和围产期细胞凋亡的影响。为了研究邻苯二甲酸酯对细胞增殖的影响，母鼠从胚胎期第 2 天（E2）到出生日（P0）每天摄入 0、1 或 5mg/kg 的邻苯二甲酸酯混合物，并在 E16 和 E17 时注射 BrdU。对后代的 mPFC 进行分析，发现暴露于邻苯二甲酸酯的组中标记细胞减少。为了研究 P5 时观察到的 BrdU 密度变化是否是由于细胞存活改变所致，我们在另一组产前暴露的后代中使用 TUNEL 测定法测量了 E18、P0 和 P5 时的细胞死亡情况。暴露于邻苯二甲酸酯的组在 E18 时 TUNEL 标记细胞增加。在最后的实验中，母鼠从 E2 到 P10 期间摄入邻苯二甲酸酯混合物，此时用 TUNEL 对 mPFC 组织进行染色。邻苯二甲酸酯处理的对象在 P10 时显示出更高密度的凋亡细胞。这些结果表明，雄性和雌性大鼠 mPFC 中均存在产前和产后邻苯二甲酸酯暴露增加细胞凋亡的现象。虽然不能排除邻苯二甲酸酯对增殖的影响，但这些数据并不能得出明确的结论。
