Department of Physiological Sciences, Stellenbosch University, Stellenbosch, South Africa.
Front Immunol. 2020 Feb 13;11:48. doi: 10.3389/fimmu.2020.00048. eCollection 2020.
Generational transfer of maladaptations in offspring have been reported to persist for multiple generations in conditions of chronic inflammation, metabolic and psychological stress. Thus, the current study aimed to expand our understanding of the nature, potential sex specificity, and transgenerational plasticity of inflammatory maladaptations resulting from maternal chronic inflammation. Briefly, F1 and F2 generations of offspring from C57/BL/6 dams exposed to a modified maternal periconception systemic inflammation (MSPI) protocol were profiled in terms of leukocyte and splenocyte counts and cytokine responses, as well as glucocorticoid sensitivity. Overall, F1 male and female LPS groups presented with glucocorticoid hypersensitivity (with elevated corticosterone and increased leukocyte glucocorticoid receptor levels) along with a pro-inflammatory phenotype, which carried over to the F2 generation. The transfer of inflammatory and glucocorticoid responsiveness from F1 to F2 is evident, with heritability of this phenotype in F2. The findings suggest that maternal (F0) perinatal chronic inflammation resulted in glucocorticoid dysregulation and a resultant pro-inflammatory phenotype, which is transferred in the maternal lineage but seems to affect male offspring to a greater extent. Of further interest, upregulation of IL-1β cytokine responses is reported in female offspring only. The cumulative maladaptation reported in F2 offspring when both F1 parents were affected by maternal LPS exposure is suggestive of immune senescence. Given the potential impact of current results and the lack of sex-specific investigations, more research in this context is urgently required.
在慢性炎症、代谢和心理压力等条件下，已经有报道称，后代的适应不良会在多代中持续存在。因此，本研究旨在扩大我们对母体慢性炎症引起的炎症适应不良的性质、潜在性别特异性和跨代可塑性的理解。简而言之，来自暴露于改良母体围产期全身炎症（MSPI）方案的 C57/BL/6 母鼠的 F1 和 F2 代后代在白细胞和脾细胞计数以及细胞因子反应以及糖皮质激素敏感性方面进行了分析。总的来说，F1 雄性和雌性 LPS 组表现出糖皮质激素超敏性（皮质酮升高和白细胞糖皮质激素受体水平升高）以及促炎表型，这种表型一直延续到 F2 代。从 F1 到 F2 的炎症和糖皮质激素反应的传递是明显的，F2 代具有这种表型的遗传性。研究结果表明，母体（F0）围产期慢性炎症导致糖皮质激素失调和由此产生的促炎表型，这种表型在母体谱系中传递，但似乎对雄性后代的影响更大。更有趣的是，仅在雌性后代中报告了 IL-1β细胞因子反应的上调。当 F1 父母都受到母体 LPS 暴露的影响时，F2 后代报告的累积适应不良表明免疫衰老。鉴于当前结果的潜在影响和缺乏性别特异性研究，迫切需要在这方面进行更多的研究。
