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孕激素烯丙孕素处理早期妊娠母马对子宫内膜和胚胎中胚胎发育和基因表达的影响。

Influences of treatment of early pregnant mares with the progestin altrenogest on embryonic development and gene expression in the endometrium and conceptus.

机构信息

Graf Lehndorff Institute for Equine Science, Brandenburg State Stud, Neustadt (Dosse), Germany.

出版信息

Theriogenology. 2011 Jul 1;76(1):61-73. doi: 10.1016/j.theriogenology.2011.01.018. Epub 2011 Mar 11.

DOI:10.1016/j.theriogenology.2011.01.018
PMID:21396689
Abstract

A positive influence of altrenogest treatment on a retarded development of the conceptus around the beginning of placentation in mares older than 8 years could be recently demonstrated. In the present study, effects of altrenogest treatment in early-pregnant mares on conceptus development and expression of endometrial and embryonic genes were investigated. Genes were chosen according to a possible involvement in embryo-maternal interaction and embryonic development in the equine species. Mares were treated with altrenogest (0.044 mg/kg bodyweight) or sunflower oil (placebo) from day 5 to 11 after ovulation. Embryos (altrenogest n = 13, placebo n = 12) and biopsies were collected on day 11. Pregnancy rate and embryonic size were not influenced by treatment (embryonic diameter: altrenogest 7.0 ± 2.5, placebo 6.5 ± 1.7 mm, n.s.). The percentage of luminal epithelial cells, superficial glandular epithelial cells and interstitial cells with nuclei staining positively for the progesterone receptor was significantly lower (P < 0.05) in samples collected from altrenogest-treated than from placebo-treated mares (e.g., luminal epithelium: altrenogest 1.9 ± 1.7%, placebo 23.0 ± 10.5%, P < 0.05). Staining for COX2 (cyclooxygenase-2) was not affected by treatment. In the endometrium a slight but significant increase in the number of PMN (polymorph nuclear neutrophils) was seen in response to treatment (altrenogest 0.8 ± 0.5 PMN/field, placebo 0.3 ± 0.3 PMN/field; P < 0.05). No differences in the relative gene expression of COX2, the receptors for progesterone, estrogens and growth hormone as well as for IGF (insulin-like growth factor) 1 and 2 were detected. The relative gene expression of aquaporin 3 in relation to β-actin differed significantly (P < 0.05) between embryos from altrenogest (3.2 ± 0.8) and placebo-treated mares (1.3 ± 0.2), but no other genes were affected. The study demonstrates down-regulation of progesterone receptors in the endometrium of early pregnant mares by treatment with the progestin altrenogest. This increased expression of aquaporin 3 in the conceptus was not related to changes in embryonic size or development.

摘要

最近的研究表明,雄激素治疗可以积极促进 8 岁以上母马胚胎在胎盘形成早期的发育。本研究旨在探讨雄激素治疗对早期妊娠母马胚胎发育和子宫内膜及胚胎基因表达的影响。根据在马属动物中可能参与胚胎-母体相互作用和胚胎发育的基因,选择了这些基因。母马在排卵后第 5 天至第 11 天接受雄激素(0.044mg/kg 体重)或葵花籽油(安慰剂)治疗。第 11 天收集胚胎(雄激素组 n = 13,安慰剂组 n = 12)和活检。治疗对妊娠率和胚胎大小没有影响(胚胎直径:雄激素 7.0 ± 2.5,安慰剂 6.5 ± 1.7mm,n.s.)。与接受安慰剂治疗的母马相比,接受雄激素治疗的母马采集的样本中,腔上皮细胞、浅层腺上皮细胞和间质细胞中孕激素受体阳性细胞核的比例显著降低(P < 0.05)(例如,腔上皮细胞:雄激素 1.9 ± 1.7%,安慰剂 23.0 ± 10.5%,P < 0.05)。COX2(环氧化酶-2)的染色不受治疗影响。在子宫内膜中,PMN(多形核中性粒细胞)的数量略有但显著增加,对治疗有反应(雄激素 0.8 ± 0.5PMN/视野,安慰剂 0.3 ± 0.3PMN/视野;P < 0.05)。未检测到 COX2、孕激素、雌激素和生长激素受体以及 IGF(胰岛素样生长因子)1 和 2 的相对基因表达存在差异。与 β-肌动蛋白相比,AQP3 的相对基因表达在雄激素(3.2 ± 0.8)和安慰剂治疗的母马胚胎(1.3 ± 0.2)之间差异显著(P < 0.05),但其他基因不受影响。该研究表明,孕激素治疗可下调早期妊娠母马子宫内膜中的孕激素受体。这种水通道蛋白 3 在胚胎中的表达增加与胚胎大小或发育无关。

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