Department of Pathology, University of Michigan Medical School, Ann Arbor, MI, USA.
Obstetrics & Gynecology Hospital of Fudan University, Shanghai, PR China.
J Pathol. 2019 Oct;249(2):206-214. doi: 10.1002/path.5308. Epub 2019 Jul 8.
Most high-grade serous carcinomas are thought to arise from Fallopian tube epithelium (FTE), but some likely arise outside of the tube, perhaps from ectopic tubal-type epithelium known as endosalpingiosis. Importantly, the origin of endosalpingiosis is poorly understood. The proximity of the tubal fimbriae to the ovaries has led to the proposal that disruptions in the ovarian surface that occur during ovulation may allow detached FTE to implant in the ovary and form tubal-type glands and cysts. An alternative model suggests that cells present in ectopic locations outside the Müllerian tract retain the capacity for multi-lineage differentiation and can form glands with tubal-type epithelium. We used double transgenic Ovgp1-iCreER ;R26R mice, which express an eYFP reporter protein in OVGP1-positive tissues following transient tamoxifen (TAM) treatment, to track the fate of oviductal epithelial cells. Cohorts of adult mice were given TAM to activate eYFP expression in oviductal epithelium, and ovaries were examined at time points ranging from 2 days to 12 months post-TAM. To test whether superovulation might increase acquisition of endosalpingiosis, additional cohorts of TAM-treated mice underwent up to five cycles of superovulation and ovaries were examined at 1, 6, and 12 months post-TAM. Ovaries were sectioned in their entirety to identify endosalpingiosis. Immunohistochemical staining for PAX8, tubulin, OVGP1, and eYFP was employed to study endosalpingiosis lesions. Ovarian endosalpingiosis was identified in 14.2% of TAM-treated adult mice. The endosalpingiotic inclusion glands and cysts were lined by secretory and ciliated cells and expressed PAX8, tubulin, OVGP1, and eYFP. Neither age nor superovulation was associated with a significant increase in endosalpingiosis. Endosalpingiosis was also occasionally present in the ovaries of pre-pubertal mice. The findings imply that ovarian endosalpingiosis in the mouse does not likely arise as a consequence of detachment and implantation of tubal epithelium and other mechanisms may be relevant. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
大多数高级别浆液性癌被认为起源于输卵管上皮（FTE），但有些可能起源于管外，可能来自称为卵管型内胚层化生的异位卵管型上皮。重要的是，卵管型内胚层化生的起源尚不清楚。输卵管伞部与卵巢的接近导致了这样的建议，即在排卵过程中卵巢表面发生的破坏可能允许分离的 FTE 植入卵巢并形成卵管型腺体和囊肿。另一种模型表明，存在于米勒管系统外异位位置的细胞保留多谱系分化的能力，并可以形成具有卵管型上皮的腺体。我们使用双转基因 Ovgp1-iCreER ；R26R 小鼠，在短暂给予他莫昔芬（TAM）治疗后，OVGP1 阳性组织中表达 eYFP 报告蛋白，来追踪输卵管上皮细胞的命运。将成年小鼠的多个队列给予 TAM 以激活输卵管上皮中的 eYFP 表达，并在 TAM 后 2 天至 12 个月的时间点检查卵巢。为了测试超排卵是否会增加卵管型内胚层化生的发生，额外的 TAM 处理的小鼠队列接受了多达五次超排卵，在 TAM 后 1、6 和 12 个月检查卵巢。将卵巢全部切片以识别卵管型内胚层化生。进行 PAX8、微管蛋白、OVGP1 和 eYFP 的免疫组织化学染色以研究卵管型内胚层化生病变。在 14.2%的 TAM 处理的成年小鼠中发现了卵巢卵管型内胚层化生。卵管型内胚层化生包含的腺体和囊肿由分泌细胞和纤毛细胞组成，表达 PAX8、微管蛋白、OVGP1 和 eYFP。年龄和超排卵均与卵管型内胚层化生的显著增加无关。在青春期前的小鼠的卵巢中偶尔也存在卵管型内胚层化生。这些发现表明，小鼠的卵巢卵管型内胚层化生不太可能是由于输卵管上皮的分离和植入引起的，其他机制可能是相关的。
