Department of Pediatrics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands; Section of Reproductive Medicine, Department of Obstetrics and Gynecology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
Department of Pathology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
Am J Pathol. 2019 Oct;189(10):2036-2045. doi: 10.1016/j.ajpath.2019.06.011. Epub 2019 Jul 29.
Bile acids (BAs) are present in ovarian follicular fluid (FF) and are linked to embryo development. However, information on the source of ovarian BA is scarce. Therefore, we aimed to explore local ovarian synthesis and BA transport from blood into FF. BA levels were determined in matching FF and serum from women undergoing in vitro fertilization. In vitro BA production by human mural granulosa cells (MGCs) and cumulus granulosa cells (CGCs) was measured by mass spectrometry. Gene and protein expression were quantified in MGC and CGC and in human ovarian tissue by quantitative PCR and Western blot/immunohistochemistry, respectively. BA levels in blood and FF were significantly correlated (r = 0.186, P = 0.027) but were almost twofold higher in FF (P < 0.001). Primary BA levels were increased in FF, indicating that, in addition to passive diffusion, other sources of ovarian BA might exist. The key BA synthesis enzyme cytochrome P450 A1 was absent in MGC and CGC; BA production in vitro was undetectable. Therefore, local ovarian BA production is unlikely. However, common BA importers (Na/taurocholate cotransporting polypeptide, apical sodium-dependent bile acid transporter) and an exporter (ATP-binding cassette subfamily C member 3) were identified in GC, theca cells, and oocyte. In summary, these results suggest that passive and active transport of BAs from blood into FF constitute sources of FF BA.
胆汁酸（BAs）存在于卵巢卵泡液（FF）中，与胚胎发育有关。然而，关于卵巢 BA 的来源的信息很少。因此，我们旨在探索局部卵巢合成和 BA 从血液向 FF 的转运。通过质谱法测定接受体外受精的女性 FF 和血清中的 BA 水平。通过质谱法测定人壁颗粒细胞（MGC）和卵丘颗粒细胞（CGC）的体外 BA 产量。通过定量 PCR 和 Western blot/免疫组织化学分别定量 MGC 和 CGC 以及人卵巢组织中的基因和蛋白表达。血液和 FF 中的 BA 水平呈显著相关（r = 0.186，P = 0.027），但 FF 中的 BA 水平几乎高出两倍（P < 0.001）。FF 中初级 BA 水平升高，表明除了被动扩散外，卵巢 BA 可能还有其他来源。关键的 BA 合成酶细胞色素 P450 A1 在 MGC 和 CGC 中缺失；体外 BA 产量无法检测到。因此，局部卵巢 BA 合成不太可能。然而，在 GC、膜细胞和卵母细胞中鉴定出了常见的 BA 摄取体（Na/牛磺胆酸钠共转运蛋白、顶端钠依赖性胆汁酸转运蛋白）和外排体（ATP 结合盒亚家族 C 成员 3）。总之，这些结果表明，BA 从血液向 FF 的被动和主动转运构成了 FF BA 的来源。
