Spann Redin A, Taylor Erin B, Welch Bradley A, Grayson Bernadette E
Department of Neurobiology and Anatomical Sciences, University of Mississippi Medical Center, Jackson, Mississippi.
Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, Mississippi.
Am J Physiol Regul Integr Comp Physiol. 2019 Dec 1;317(6):R852-R863. doi: 10.1152/ajpregu.00230.2019. Epub 2019 Nov 6.
Obesity in women results in reduced fertility and increased complications during pregnancy. Vertical sleeve gastrectomy (VSG) effectively reduces weight, type 2 diabetes, and dyslipidemia, but is also associated with preterm and small-for-gestational age births. The mechanism by which VSG influences fetal development remains unknown. Here we hypothesize that previously reported immune changes during rat VSG pregnancy are reflected long term in the immune system of the offspring. Offspring of VSG and sham dams were evaluated at postnatal day (PND) 21 and PND60. At PND21, VSG pups have lower numbers of circulating B lymphocytes compared with sham pups ( < 0.05) and have lower transcription of lymphocyte marker ( < 0.01) in the spleen, while other lymphocyte populations measured are not different. Total plasma IgG is higher ( < 0.01) and C-reactive protein is lower ( < 0.05) in VSG offspring compared with sham offspring at PND21. The central nervous system of VSG pups is also affected at PND21, having higher expression of mRNA ( < 0.05) and higher immunoreactivity of microglia marker, IBA1, in the hypothalamus. At PND60, the immune-hematological differences are not present; however, mRNA expression of is elevated ( < 0.001) in the spleen of VSG offspring along with markers of T cells. These data suggest that the immune system of VSG offspring is compromised early in life, but rebounds after weaning and may even become hyperactive. Future work is needed to determine whether the immune system of VSG offspring is capable of mounting a proper defense and whether other aspects of development are affected.
女性肥胖会导致生育能力下降以及孕期并发症增加。垂直袖状胃切除术（VSG）能有效减轻体重、改善2型糖尿病和血脂异常，但也与早产和小于胎龄儿出生有关。VSG影响胎儿发育的机制尚不清楚。在此，我们假设先前报道的大鼠VSG孕期免疫变化会在后代免疫系统中得到长期反映。对VSG和假手术母鼠的后代在出生后第21天（PND21）和第60天（PND60）进行评估。在PND21时，与假手术组幼崽相比，VSG组幼崽循环B淋巴细胞数量更低（<0.05），脾脏中淋巴细胞标志物的转录水平更低（<0.01），而所检测的其他淋巴细胞群体无差异。与假手术组后代相比，VSG组后代在PND21时血浆总IgG更高（<0.01），C反应蛋白更低（<0.05）。VSG组幼崽的中枢神经系统在PND21时也受到影响，下丘脑中有更高的mRNA表达（<0.05）以及小胶质细胞标志物IBA1的免疫反应性更高。在PND60时，免疫血液学差异不存在；然而，VSG组后代脾脏中mRNA的表达升高（<0.001），同时伴有T细胞标志物升高。这些数据表明，VSG组后代的免疫系统在生命早期受到损害，但断奶后会反弹，甚至可能变得过度活跃。需要进一步的研究来确定VSG组后代的免疫系统是否能够进行适当的防御，以及发育的其他方面是否受到影响。
