Lipopolysaccharide Reduces the Primordial Follicle Pool in the Bovine Ovarian Cortex Ex Vivo and in the Murine Ovary In Vivo
Lipopolysaccharide Reduces the Primordial Follicle Pool in the Bovine Ovarian Cortex Ex Vivo and in the Murine Ovary In Vivo
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DOI：
10.1095/biolreprod.112.106914
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发表时间：
2013-04-01
影响因子：
3.6
通讯作者：
Sheldon, I. Martin
中科院分区：
文献类型：
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作者：
Bromfield, John J.;Sheldon, I. Martin
子宫或乳腺感染革兰氏阴性菌会导致牛不育，不仅在患病期间，而且在患病后一段时间内也会如此。即使这些感染发生在远离卵巢的器官，子宫炎和乳腺炎也会扰乱体内窦卵泡的发育和功能。虽然来自窦卵泡的颗粒细胞表达Toll样受体4（TLR 4），并检测和产生对来自革兰氏阴性菌的脂多糖（LPS）的炎症反应，但尚不清楚LPS是否影响窦前卵泡发育。本研究验证了LPS干扰原始卵泡发育的假设。牛卵巢皮质离体暴露于LPS减少了与原始卵泡激活增加相关的原始卵泡池。卵巢皮质培养上清液以LPS浓度依赖性方式积累炎症介质IL-1 β、IL-6和IL-8。此外，LPS暴露调节卵泡激活的关键细胞内调节因子，导致原始卵泡PTEN丢失和FOXO 3胞质易位。小鼠体内急性暴露于LPS也减少了与卵泡闭锁增加相关的原始卵泡池。增加的卵泡闭锁是TLR 4依赖性的，因为Tlr 4缺陷小鼠对LPS介导的卵泡闭锁不敏感。然而，LPS不影响单独培养的牛次级卵泡或其封闭的卵母细胞的直径。总之，LPS减少了原始卵泡池在牛卵巢皮质离体和在小鼠卵巢在体内。这些观察结果提供了一个深入了解如何远离卵巢的细菌感染对生育能力的长期影响。
Infections of the uterus or mammary gland with Gram-negative bacteria cause infertility in cattle, not only during disease but also for some time afterward. Even though these infections are in organs distant from the ovary, metritis and mastitis perturb antral follicle development and function in vivo. Although granulosa cells from antral follicles express toll-like receptor 4 (TLR4), and detect and mount an inflammatory response to lipopolysaccharide (LPS) from Gram-negative bacteria, it is not known whether LPS impacts preantral follicle development. The present study tested the hypothesis that LPS perturbs the development of primordial ovarian follicles. Exposure of bovine ovarian cortex ex vivo to LPS reduced the primordial follicle pool associated with increased primordial follicle activation. Ovarian cortex culture supernatants accumulated the inflammatory mediators IL-1beta, IL-6, and IL-8 in an LPS concentration-dependent manner. In addition, LPS exposure modulated key intracellular regulators of follicle activation with loss of the primordial follicle PTEN and cytoplasmic translocation of FOXO3. Acute exposure of mice in vivo to LPS also reduced the primordial follicle pool associated with increased follicle atresia. The increased follicle atresia was TLR4-dependent as Tlr4-deficient mice were insensitive to LPS-mediated follicle atresia. However, LPS did not affect the diameter of individually cultured bovine secondary follicles or their enclosed oocytes. In conclusion, LPS reduced the primordial ovarian follicle pool in the bovine ovarian cortex ex vivo and in the murine ovary in vivo. These observations provide an insight into how bacterial infections distant from the ovary have long term effects on fertility.