Cheng Wanpeng, Zhang Lantian, Sa Peiyue, Luo Jing, Li Mengdi
Jiangsu Key Laboratory of Immunity and Metabolism, Department of Pathogen Biology and Immunology, Xuzhou Medical University, Xuzhou 221004, Jiangsu, China.
Department of Anatomy, Basic Medical College, Xuzhou Medical University, Xuzhou 221004, Jiangsu, China.
Metallomics. 2022 Sep 12;14(9). doi: 10.1093/mtomcs/mfac062.
Selenium deficiency has been considered to increase the risk of gestational complications. Our previous work showed that maternal selenium deficiency suppressed proliferation, induced autophagy dysfunction, and apoptosis in the placenta of mice. However, other effects of maternal selenium deficiency on the placenta and the underlying mechanisms remain unclear. In the present study, dietary selenium deficiency in dams significantly suppressed glutathione peroxidase (GSH-Px) activity, total antioxidant capacity (T-AOC), and increased malondialdehyde (MDA) content in the placentae, confirming the oxidative stress in the placenta. By transcriptome sequencing analysis, the DEGs were involved in many biological processes, including ion transport, lipid metabolic process, immune response, transmembrane transport, and others. According to the KEGG analysis, the DEGs were primarily enriched in metabolic pathways, PI3K-Akt signaling pathway, and others. Among these, the steroid hormone biosynthesis pathway enriched the most DEGs. Hsd3b1, an ER enzyme involved in progesterone synthesis, was validated downregulated. Consistently, the progesterone content in the serum of the selenium-deficient group was decreased. Ion transporters and transmembrane transporters, such as Heph, Trf, Slc39a8, Slc23a1, Atp7b, and Kcnc1, were reduced in the selenium-deficient placentae. Immune response-related genes, including Ccl3, Ccl8, Cxcl10, and Cxcl14, were increased in the selenium-deficient placentae, along with an increase in macrophage number. These results suggested that maternal selenium deficiency may impair progesterone biosynthesis, reduce nutrient transporters expression, and promote immune response by increasing the oxidative stress of the placentae. This present study provides a novel insight into the possible cause of placenta disorder during pregnancy.
硒缺乏被认为会增加妊娠并发症的风险。我们之前的研究表明，母体硒缺乏会抑制小鼠胎盘的增殖，诱导自噬功能障碍和细胞凋亡。然而，母体硒缺乏对胎盘的其他影响及其潜在机制仍不清楚。在本研究中，母鼠饮食中硒缺乏显著抑制了胎盘谷胱甘肽过氧化物酶（GSH-Px）活性、总抗氧化能力（T-AOC），并增加了丙二醛（MDA）含量，证实了胎盘存在氧化应激。通过转录组测序分析，差异表达基因（DEGs）参与了许多生物学过程，包括离子转运、脂质代谢过程、免疫反应、跨膜转运等。根据KEGG分析，DEGs主要富集在代谢途径、PI3K-Akt信号通路等。其中，类固醇激素生物合成途径富集的DEGs最多。参与孕酮合成的内质网酶Hsd3b1被证实下调。同样，硒缺乏组血清中的孕酮含量降低。在硒缺乏的胎盘中，离子转运体和跨膜转运体，如Heph、Trf、Slc39a8、Slc23a1、Atp7b和Kcnc1减少。与免疫反应相关的基因，包括Ccl3、Ccl8、Cxcl10和Cxcl14，在硒缺乏的胎盘中增加，同时巨噬细胞数量增加。这些结果表明，母体硒缺乏可能通过增加胎盘的氧化应激损害孕酮生物合成，降低营养转运体表达，并促进免疫反应。本研究为孕期胎盘疾病的可能原因提供了新的见解。
