1 Department of Histology and Embryology, Faculty of Medicine, Dokuz Eylül University, Izmir, Turkey.
2 Department of Obstetrics and Gynecology, Faculty of Medicine, Celal Bayar University, Manisa, Turkey.
Reprod Sci. 2019 Jan;26(1):128-138. doi: 10.1177/1933719118766266. Epub 2018 Apr 9.
α-Lipoic acid (ALA) is a safe natural molecule involved in the immunomodulation of many physiological processes. Orally administered ALA has been reported to treat several inflammatory pathologies and support pregnancy. Our study aimed at testing ALA vaginal administration in female Wistar rats evaluating its tissue distribution (experiment I), impact on implantation process (experiment II), and effectiveness in contrasting induced preterm birth (experiment III). In experiment I, rats were intravaginally treated with 50 mg/kg or 500 mg/kg ALA, or with a physiologic solution, for 4 days. α-Lipoic acid distribution in uterus and cervical tissues was evaluated by immunohistochemical analyses. In experiment II, rats received intravaginally the above treatments for 5 days, then they were mated and, if pregnant, included in the experiment to evaluate both implantation rate and the content of implantation mediators in uterus tissues. In experiment III, pregnant rats were pretreated with placebo or with vaginal ALA for 4 days and then induced to delivery with mifepristone plus PGE2 on the 19th day of pregnancy. The delivery time was recorded, and the messenger RNA (mRNA) levels of pro-inflammatory cytokines were detected in the uterine tissues by real-time polymerase chain reaction. Immunohistochemistry was also performed. Results showed that vaginal ALA was well absorbed and distributed. The treatment did not affect the implantation process and was able to significantly revert mifepristone plus prostaglandin E2 effects, delaying the timing of delivery and significantly decreasing mRNA synthesis and release of pro-inflammatory cytokines. We provide for the first time new information on vaginal ALA use, even during pregnancy, opening a perspective for further studies.
α-硫辛酸（ALA）是一种安全的天然分子，参与许多生理过程的免疫调节。口服 ALA 已被报道可治疗多种炎症性疾病并支持妊娠。我们的研究旨在测试 ALA 阴道给药在雌性 Wistar 大鼠中的作用，评估其组织分布（实验 I）、对植入过程的影响（实验 II）以及在对抗诱导早产中的效果（实验 III）。在实验 I 中，大鼠阴道内给予 50mg/kg 或 500mg/kg 的 ALA 或生理溶液，连续 4 天。通过免疫组织化学分析评估 ALA 在子宫和宫颈组织中的分布。在实验 II 中，大鼠接受上述阴道内治疗 5 天，然后交配，如果怀孕，则将其纳入实验以评估植入率和子宫组织中植入介质的含量。在实验 III 中，怀孕大鼠用安慰剂或阴道 ALA 预处理 4 天，然后在妊娠第 19 天用米非司酮加 PGE2 诱导分娩。记录分娩时间，并通过实时聚合酶链反应检测子宫组织中促炎细胞因子的信使 RNA（mRNA）水平。还进行了免疫组织化学分析。结果表明，阴道 ALA 被很好地吸收和分布。该治疗不影响植入过程，并且能够显著逆转米非司酮加前列腺素 E2 的作用，延迟分娩时间，并显著降低促炎细胞因子的 mRNA 合成和释放。我们首次提供了阴道 ALA 即使在怀孕期间使用的新信息，为进一步研究开辟了前景。
