Laboratory of Endocrine System Development, A.P. Avtsyn Research Institute of Human Morphology of Federal State Budgetary Scientific Institution "Petrovsky National Research Center of Surgery", 119991 Moscow, Russia.
Department of Human Anatomy and Histology, Federal State Funded Educational Institution of Higher Education I.M. Sechenov First Moscow State Medical University, 119435 Moscow, Russia.
Int J Mol Sci. 2023 Feb 1;24(3):2774. doi: 10.3390/ijms24032774.
Dichlorodiphenyltrichloroethane (DDT) is the most widespread persistent pollutant with endocrine-disrupting properties. DDT has been shown to disrupt secretory and morphogenetic processes in the adrenal cortex. The present investigation aimed to evaluate transcriptional regulation of postnatal growth of the adrenal medulla and formation of the pools necessary for self-renewal of medullary cells in rats that developed under low-dose exposure to DDT. The study was performed using male Wistar rats exposed to low doses of o,p'-DDT during prenatal and postnatal development. Light microscopy and histomorphometry revealed diminished medulla growth in the DDT-exposed rats. Evaluation of Ki-67 expression in chromaffin cells found later activation of proliferation indicative of retarded growth of the adrenal medulla. All DDT-exposed rats exhibited a gradual decrease in tyrosine hydroxylase production by adrenal chromaffin cells. Immunohistochemical evaluation of nuclear β-catenin, transcription factor Oct4, and ligand of sonic hedgehog revealed increased expression of all factors after termination of growth in the control rats. The DDT-exposed rats demonstrated diminished increases in Oct4 and sonic hedgehog expression and lower levels of canonical Wnt signaling activation. Thus, developmental exposure to the endocrine disruptor o,p'-DDT alters the transcriptional regulation of morphogenetic processes in the adrenal medulla and evokes a slowdown in its growth and in the formation of a reserve pool of cells capable of dedifferentiation and proliferation that maintain cellular homeostasis in adult adrenals.
滴滴涕（DDT）是分布最广泛的具有内分泌干扰特性的持久性污染物。DDT 已被证明会干扰肾上腺皮质的分泌和形态发生过程。本研究旨在评估在低剂量滴滴涕暴露下发育的大鼠肾上腺髓质的出生后生长和髓质细胞自我更新所需的池形成的转录调控。该研究使用雄性 Wistar 大鼠进行，这些大鼠在产前和产后发育过程中暴露于低剂量 o,p'-DDT。光镜和组织形态计量学显示，DDT 暴露组的髓质生长减少。在嗜铬细胞中评估 Ki-67 表达发现增殖的后期激活，表明肾上腺髓质的生长迟缓。所有 DDT 暴露组的大鼠均表现出肾上腺嗜铬细胞中酪氨酸羟化酶产生的逐渐减少。对核 β-连环蛋白、转录因子 Oct4 和 sonic hedgehog 配体的免疫组织化学评估显示，在对照大鼠生长停止后，所有因子的表达均增加。DDT 暴露组大鼠的 Oct4 和 sonic hedgehog 表达增加减少，经典 Wnt 信号通路的激活水平降低。因此，发育暴露于内分泌干扰物 o,p'-DDT 会改变肾上腺髓质形态发生过程的转录调控，并导致其生长减缓以及形成能够去分化和增殖的细胞储备池的能力降低，从而维持成年肾上腺的细胞内稳态。
