Age-related oxidative modifications to uterine albumin impair extravillous trophoblast cells function.,Free Radical Biology and Medicine

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Age-related oxidative modifications to uterine albumin impair extravillous trophoblast cells function.
Free Radical Biology and Medicine ( IF 7.1 ) Pub Date : 2020-03-26 , DOI: 10.1016/j.freeradbiomed.2020.03.020
S Mendes ₁ , F Timóteo-Ferreira ₁ , A I Soares ₁ , A R Rodrigues ₁ , A M N Silva ₂ , S Silveira ₃ , L Matos ₄ , J Saraiva ₅ , L Guedes-Martins ₅ , H Almeida ₆ , E Silva ₁

Affiliation

Ageing and Stress, Instituto de Biologia Molecular e Celular, Instituto de Investigação e Inovação Em Saúde, Universidade do Porto, Rua Alfredo Allen 208, 4200-135, Porto, Portugal; Unidade de Biologia Experimental, Departamento de Biomedicina, Faculdade de Medicina, Universidade do Porto, Alameda Professor Hernâni Monteiro, 4200-319, Porto, Portugal.
REQUIMTE-LAQV, Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade do Porto, Rua do Campo Alegre, s/n, 4169-007, Porto, Portugal.
Unidade de Biologia Experimental, Departamento de Biomedicina, Faculdade de Medicina, Universidade do Porto, Alameda Professor Hernâni Monteiro, 4200-319, Porto, Portugal.
Ageing and Stress, Instituto de Biologia Molecular e Celular, Instituto de Investigação e Inovação Em Saúde, Universidade do Porto, Rua Alfredo Allen 208, 4200-135, Porto, Portugal; Faculdade de Medicina Dentária, Universidade do Porto, Rua Dr. Manuel Pereira da Silva, 4200-393, Porto, Portugal; Faculdade de Ciências da Nutrição e Alimentação, Universidade do Porto, Rua Dr. Roberto Frias, 4200-465, Porto, Portugal.
Ageing and Stress, Instituto de Biologia Molecular e Celular, Instituto de Investigação e Inovação Em Saúde, Universidade do Porto, Rua Alfredo Allen 208, 4200-135, Porto, Portugal; Departamento da Mulher e da Medicina Reprodutiva, Centro Hospitalar do Porto EPE, Largo Prof. Abel Salazar, 4099-001, Porto, Portugal.
Ageing and Stress, Instituto de Biologia Molecular e Celular, Instituto de Investigação e Inovação Em Saúde, Universidade do Porto, Rua Alfredo Allen 208, 4200-135, Porto, Portugal; Unidade de Biologia Experimental, Departamento de Biomedicina, Faculdade de Medicina, Universidade do Porto, Alameda Professor Hernâni Monteiro, 4200-319, Porto, Portugal; Ginecologia-Obstetrícia, Hospital-CUF Porto, Estrada da Circunvalação 14341, 4100-180, Porto, Portugal.

Advanced maternal age is associated not only with a significant reduction in fertility but also with an additional risk of developing pregnancy-related disorders. Most of these disorders are now believed to be the clinical manifestation of an incorrect placentation, namely deficient transformation of maternal spiral arteries and ineffective trophoblast invasion through uterine stroma. In the present study it was hypothesized that an age-related loss in uterine redox homeostasis interferes with the function of extravillous trophoblasts (EVTs) and placentation. To test this hypothesis, relative levels of oxidatively modified proteins were evaluated in human samples from placenta and placental bed, and the role of specific oxidative modifications to proteins in placentation was studied using a cell culture model of EVTs. In the placental bed, the carbonylation level of a 66 kDa protein (identified as albumin) presented a strong, positive and significant correlation with maternal age. Albumin was immunodetected preferentially in endothelial cells and connective tissue between muscle fascicles. In vitro results showed that carbonylated albumin overload did not alter cell viability, but reduced EVTs motility and triggered cell stress response pathways. Moreover, EVTs presented decreased ability to adhere to and invade a collagen extracellular matrix pre-treated with carbonylated albumin. In conclusion, reproductive ageing is accompanied by an increase in maternal uterine carbonylated albumin, that may have a deleterious role in the modulation of EVTs function.

中文翻译：

与年龄相关的子宫白蛋白氧化修饰会损害绒毛外滋养层细胞的功能。

高龄产妇不仅与生育能力显着降低有关，而且与患妊娠相关疾病的风险增加有关。这些疾病中的大多数现在被认为是不正确胎盘的临床表现，即母体螺旋动脉的转化不足和通过子宫基质的滋养层侵入无效。在本研究中，假设与年龄相关的子宫氧化还原稳态丧失会干扰绒毛外滋养细胞 (EVT) 和胎盘的功能。为了验证这一假设，我们在来自胎盘和胎盘床的人体样本中评估了氧化修饰蛋白的相对水平，并使用 EVT 的细胞培养模型研究了特定氧化修饰蛋白在胎盘形成中的作用。在胎盘床上，一个 66 kDa 的蛋白质（被确定为白蛋白）的羰基化水平与母亲的年龄呈现出强烈、正向和显着的相关性。白蛋白优先在内皮细胞和肌肉束之间的结缔组织中进行免疫检测。体外结果表明，羰基化白蛋白超载不会改变细胞活力，但会降低 EVT 的运动性并触发细胞应激反应途径。此外，EVT 表现出粘附和侵入用羰基化白蛋白预处理的胶原细胞外基质的能力降低。总之，生殖衰老伴随着母体子宫羰基化白蛋白的增加，这可能对调节 EVT 功能具有有害作用。与产妇年龄呈显着正相关。白蛋白优先在内皮细胞和肌肉束之间的结缔组织中进行免疫检测。体外结果表明，羰基化白蛋白超载不会改变细胞活力，但会降低 EVT 的运动性并触发细胞应激反应途径。此外，EVT 表现出粘附和侵入用羰基化白蛋白预处理的胶原细胞外基质的能力降低。总之，生殖衰老伴随着母体子宫羰基化白蛋白的增加，这可能对调节 EVT 功能具有有害作用。与产妇年龄呈显着正相关。白蛋白优先在内皮细胞和肌肉束之间的结缔组织中进行免疫检测。体外结果表明，羰基化白蛋白超载不会改变细胞活力，但会降低 EVT 的运动性并触发细胞应激反应途径。此外，EVT 表现出粘附和侵入用羰基化白蛋白预处理的胶原细胞外基质的能力降低。总之，生殖衰老伴随着母体子宫羰基化白蛋白的增加，这可能对调节 EVT 功能具有有害作用。但降低了 EVT 的运动性并触发了细胞应激反应途径。此外，EVT 表现出粘附和侵入用羰基化白蛋白预处理的胶原细胞外基质的能力降低。总之，生殖衰老伴随着母体子宫羰基化白蛋白的增加，这可能对调节 EVT 功能具有有害作用。但降低了 EVT 的运动性并触发了细胞应激反应途径。此外，EVT 表现出粘附和侵入用羰基化白蛋白预处理的胶原细胞外基质的能力降低。总之，生殖衰老伴随着母体子宫羰基化白蛋白的增加，这可能对调节 EVT 功能具有有害作用。

更新日期：2020-03-27

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