Rebordão Maria R, Galvão António, Pinto-Bravo Pedro, Pinheiro Joana, Gamboa Sandra, Silva Elisabete, Mateus Luísa, Ferreira-Dias Graça
CIISA, Faculty of Veterinary Medicine, University of Lisbon, Lisbon, Portugal; Department of Animal Science, Coimbra College of Agriculture, Coimbra, Portugal.
CIISA, Faculty of Veterinary Medicine, University of Lisbon, Lisbon, Portugal; Department of Reproductive Immunology and Pathology, Institute of Animal Reproduction and Food Research of PAS, Olsztyn, Poland.
Theriogenology. 2017 Jan 1;87:193-204. doi: 10.1016/j.theriogenology.2016.08.028. Epub 2016 Sep 8.
Oxytocin (OXT) has been used to prolong the luteal phase in mares, but its mechanism of action is unknown. The aim of this study was to evaluate the effect of chronic exogenous OXT administration to mid-luteal phase mares on luteal maintenance. Also, endometrial expression of prostaglandin endoperoxide synthase 2 (PTGS2), prostaglandin Fα, E and I synthases (AKR1C3, PTGES, and PTGIS), oxytocin receptor (OXTR), progesterone receptor (PGR), and estrogen receptors 1 (ESR1) and 2 (ESR2) were assessed in mares experiencing luteal maintenance 2 weeks after chronic exogenous OXT administration. Control mares (n = 5; C group) received 6 mL of saline im, whereas OXT (60 units/mare) was administered im (n = 6; OXT group), every 12 hours, on days 7 to 14 postovulation. After endometrial biopsy in groups C (Day 10) and OXT (Day 24), luteolysis occurred within 3 or 6 days, respectively. Luteal maintenance took place in 4 of 6 (67%) of OXT-treated mares. Progesterone in C group was the highest on biopsy day (P < 0.05). In OXT mares, PTGS2, ESR1 (P < 0.05), PTGES, PTGIS, PGR, and ESR2 (P < 0.01) gene transcription decreased, whereas OXTR increased (P < 0.05) in comparison with the C group. In OXT-treated mares, endometrial ESR2 protein expression decreased (P < 0.05), but OXTR increased (P < 0.05) compared with control animals. In both experimental groups, PTGS2 was mainly immunolocalized in surface epithelium, whereas AKR1C3, PTGES, PTGIS, and PGR were in surface and glandular epithelia. ESR1 and ESR2 were found in glandular epithelium and OXTR in stromal cells. High immunolabeling for PTGES, PTGIS, PGR, and OXTR and low for ESR2 was detected in endometrium of OXT-group mares with extended diestrus. Prolonged luteal function associated with chronic OXT treatment may be related to different spatial expression of OXTR and PGR in the endometrium. The observed reduction of endometrial ESR2 may be responsible for the maintenance of PGR in luminal and glandular epithelium. Also, ESR2 may attenuate the transcriptional activity of ESR1 in mare endometrium. This study offers new knowledge on the endometrial expression of ovarian steroids and OXT receptors in OXT pharmacologically induced luteal maintenance in the mare.
催产素（OXT）已被用于延长母马的黄体期，但其作用机制尚不清楚。本研究的目的是评估在黄体中期向母马长期外源性给予OXT对黄体维持的影响。此外，在长期外源性给予OXT 2周后经历黄体维持的母马中，评估了前列腺素内过氧化物合酶2（PTGS2）、前列腺素Fα、E和I合酶（AKR1C3、PTGES和PTGIS）、催产素受体（OXTR）、孕酮受体（PGR）以及雌激素受体1（ESR1）和2（ESR2）的子宫内膜表达。对照组母马（n = 5；C组）肌肉注射6 mL生理盐水, 而OXT组（n = 6）在排卵后第7至14天每12小时肌肉注射一次OXT（60单位/母马）。在C组（第10天）和OXT组（第24天）进行子宫内膜活检后，分别在3天或6天内发生黄体溶解。6匹接受OXT治疗的母马中有4匹（67%）维持了黄体。C组在活检日的孕酮水平最高（P < 0.05）。与C组相比，OXT组母马的PTGS2、ESR1（P < 0.05）、PTGES、PTGIS、PGR和ESR2（P < 0.01）基因转录减少，而OXTR增加（P < 0.05）。与对照动物相比，在接受OXT治疗的母马中，子宫内膜ESR2蛋白表达降低（P < 0.05），但OXTR增加（P < 0.05）。 在两个实验组中，PTGS2主要免疫定位在表面上皮，而AKR1C3、PTGES、PTGIS和PGR在表面和腺上皮中。ESR1和ESR2存在于腺上皮中，OXTR存在于基质细胞中。在发情间期延长的OXT组母马的子宫内膜中，检测到PTGES、PTGIS、PGR和OXTR的高免疫标记以及ESR2的低免疫标记。与慢性OXT治疗相关的黄体功能延长可能与子宫内膜中OXTR和PGR的不同空间表达有关。观察到的子宫内膜ESR2的减少可能是维持腔上皮和腺上皮中PGR的原因。此外，ESR2可能会减弱母马子宫内膜中ESR1的转录活性。本研究为药理学诱导母马黄体维持过程中卵巢类固醇和OXT受体的子宫内膜表达提供了新知识。
