Corticosteroids have been utilised in the assisted reproduction setting with the expectation of suppressing aberrant immune activation and improving fertility in women. However, the effects of corticosteroids on fertility, and on pregnancy and offspring outcomes, are unclear. In this study, mice were administered prednisolone (1 mg/kg) or PBS daily in the pre-implantation phase, and effects on the adaptive immune response, the implantation rate, fetal development and postnatal outcomes were investigated. Prednisolone disrupted the expected expansion of CD4+ T cells in early pregnancy, inhibiting generation of both regulatory T cells (Treg cells) and effector T cells and suppressing IFNG required for T cell functional competence. Prednisolone caused an 8-20% increase in the embryo implantation rate and increased the number of viable pups per litter. In late gestation, fetal and placental weights were reduced in a litter size-dependent manner, and the canonical inverse relationship between litter size and fetal weight was lost. The duration of pregnancy was extended by ~ 0.5 day and birth weight was reduced by ~ 5% after prednisolone treatment. Viability of prednisolone-exposed offspring was comparable to controls, but body weight was altered in adulthood, particularly in male offspring. Thus, while prednisolone given in the pre-implantation phase in mice increases maternal receptivity to implantation and resource investment in fetal growth, there is a trade-off in long-term consequences for fetal development, birth weight and offspring health. These effects are associated with, and likely caused by, prednisolone suppression of the adaptive immune response at the outset of pregnancy.

中文翻译：

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妊娠早期的泼尼松龙抑制调节性 T 细胞生成并改变小鼠的胎儿和胎盘发育。

皮质类固醇已被用于辅助生殖环境，以期抑制异常免疫激活并提高女性的生育能力。然而，皮质类固醇对生育能力、妊娠和后代结局的影响尚不清楚。在这项研究中，小鼠在植入前阶段每天服用泼尼松龙 (1 mg/kg) 或 PBS，并研究对适应性免疫反应、植入率、胎儿发育和出生后结果的影响。泼尼松龙破坏了妊娠早期 CD4+ T 细胞的预期扩增，抑制了调节性 T 细胞（Treg 细胞）和效应 T 细胞的生成，并抑制了 T 细胞功能所需的 IFNG。泼尼松龙使胚胎植入率增加了 8-20%，并增加了每窝可存活幼崽的数量。在妊娠晚期，胎儿和胎盘重量以窝产仔数依赖的方式减少，窝产仔数和胎儿体重之间的典型反比关系消失。泼尼松龙治疗后，妊娠持续时间延长了约 0.5 天，出生体重减少了约 5%。暴露于泼尼松龙的后代的生存能力与对照组相当，但成年后体重发生了变化，尤其是雄性后代。因此，虽然在小鼠植入前阶段给予泼尼松龙增加了母体对植入的接受度和胎儿生长的资源投资，但在胎儿发育、出生体重和后代健康的长期后果方面存在权衡。这些影响与妊娠开始时泼尼松龙对适应性免疫反应的抑制有关，并可能由其引起。