Zika virus (ZIKV) infection is associated with adverse pregnancy outcomes in humans, and infection in the first trimester can lead to miscarriage and stillbirth. Vertical and sexual transmissions of ZIKV have been demonstrated, yet the impact of infection during the initial stages of pregnancy remains unexplored. Here we defined the impact of ZIKV on early embryonic and placental development with a rhesus macaque model. During in vitro fertilization (IVF), macaque gametes were inoculated with a physiologically relevant dose of 5.48log₁₀ plaque-forming units (PFU) of Zika virus/H.sapiens-tc/PUR/2015/PRVABC59_v3c2. Exposure at fertilization did not alter blastocyst formation rates compared to controls. To determine the impact of ZIKV exposure at implantation, hatched blastocysts were incubated with 3.26log₁₀, 4.26log₁₀, or 5.26log₁₀ PFU, or not exposed to ZIKV, followed by extended embryo culture for 10 days. ZIKV exposure negatively impacted attachment, growth, and survival in comparison to controls, with exposure to 5.26log₁₀ PFU ZIKV resulting in embryonic degeneration by day 2. Embryonic secretion of pregnancy hormones was lower in ZIKV-exposed embryos. Increasing levels of infectious virus were detected in the culture media post-exposure, suggesting that the trophectoderm is susceptible to productive ZIKV infection. These results demonstrate that ZIKV exposure severely impacts the zona-free blastocyst, whereas exposure at the time of fertilization does not hinder blastocyst formation. Overall, early stages of pregnancy may be profoundly sensitive to infection and pregnancy loss, and the negative impact of ZIKV infection on pregnancy outcomes may be underestimated.

中文翻译：

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寨卡病毒对恒河猴体外植入模型的胚胎毒性影响†。

寨卡病毒 (ZIKV) 感染与人类的不良妊娠结局有关，妊娠头三个月的感染可导致流产和死产。ZIKV 的垂直传播和性传播已经得到证实，但在怀孕初期感染的影响仍有待探索。在这里，我们使用恒河猴模型定义了 ZIKV 对早期胚胎和胎盘发育的影响。在体外受精 (IVF) 过程中，猕猴配子接种了生理相关剂量的 5.48log _{10 个}斑块形成单位 (PFU) 的寨卡病毒/H.sapiens-tc/PUR/2015/PRVABC59_v3c2。与对照相比，受精时的暴露不会改变囊胚形成率。为了确定 ZIKV 在着床时暴露的影响，孵化的囊胚与 3.26log₁₀，4.26log ₁₀，或5.26log ₁₀ PFU，或不暴露于ZIKV，随后扩展胚胎培养10天。与对照组相比，ZIKV 暴露对附着、生长和存活产生负面影响，暴露于 5.26log ₁₀PFU ZIKV 导致第 2 天胚胎退化。在暴露于 ZIKV 的胚胎中，妊娠激素的胚胎分泌较低。在暴露后的培养基中检测到感染性病毒的水平增加，表明滋养外胚层容易受到生产性 ZIKV 感染。这些结果表明，ZIKV 暴露严重影响无带囊胚，而在受精时暴露不会阻碍囊胚形成。总体而言，妊娠早期可能对感染和流产极为敏感，可能低估了 ZIKV 感染对妊娠结局的负面影响。