We have demonstrated that tadalafil facilitates fetal growth in mice with L-NG-nitroarginine methyl ester (L-NAME)-induced preeclampsia (PE) with fetal growth restriction (FGR). Tadalafil is a selective phosphodiesterase 5 inhibitor that dilates the maternal blood sinuses in the placenta, thereby facilitating the growth of the fetus. The purpose of this study was to investigate the effects of tadalafil treatment for PE and FGR on the developing brain in FGR offspring using an L-NAME-induced mouse model of PE with FGR. A control group of dams received carboxymethylcellulose (CMC). L-NAME-treated groups received L-NAME dissolved in CMC from 11 days post coitum (d.p.c.). The L-NAME-treated dams were divided into two subgroups 14 d.p.c. One subgroup continued to receive L-NAME. The other subgroup received L-NAME with tadalafil suspended in CMC. Tadalafil treatment for PE with FGR reduced the expression of hypoxia-inducible factor-2α in the placenta and in the brain of the FGR fetus. Moreover, tadalafil treatment in utero shows improved synaptogenesis and myelination in FGR offspring on postnatal day 15 (P15) and P30. These results suggest that tadalafil treatment for PE with FGR not only facilitates fetal growth, but also has neuroprotective effects on the developing brain of FGR offspring through modulating prenatal hypoxic conditions.

中文翻译：

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他达拉非对子痫前期胎儿生长受限的小鼠的治疗通过调节产前低氧状况对后代具有神经有益作用

我们已经证明，他达拉非可促进具有L-NG-硝基精氨酸甲酯（L-NAME）诱导的先兆子痫（PE）的胎儿生长受限（FGR）的小鼠的胎儿生长。他达拉非是一种选择性磷酸二酯酶5抑制剂，可扩张胎盘中的母亲血液窦，从而促进胎儿的生长。这项研究的目的是使用L-NAME诱导的带有FGR的PE小鼠模型，研究他达拉非治疗PE和FGR对FGR后代发育中的大脑的影响。大坝对照组接受羧甲基纤维素（CMC）。L-NAME治疗组从Coitum（dpc）后11天开始接受溶解在CMC中的L-NAME。经L-NAME处理的水坝分为两个子组14 dpc一个子组继续获得L-NAME。另一个小组收到了L-NAME，他达拉非被暂停在CMC中。他达拉非用FGR治疗PE可以降低FGR胎儿胎盘和大脑中缺氧诱导因子2α的表达。而且，他达拉非在子宫内的治疗显示出产后第15天（P15）和P30的FGR后代的突触发生和髓鞘形成改善。这些结果表明他达拉非用FGR治疗PE不仅促进胎儿生长，而且通过调节产前低氧条件对FGR后代的大脑发育具有神经保护作用。