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胎盘中炎症时马胎盘的类固醇合成和代谢。

Steroid synthesis and metabolism in the equine placenta during placentitis.

机构信息

Maxwell H. Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, Kentucky, USA.

Theriogenology Department, Faculty of Veterinary Medicine, University of Mansoura, Mansoura, Egypt.

出版信息

Reproduction. 2020 Mar;159(3):289-302. doi: 10.1530/REP-19-0420.

DOI:10.1530/REP-19-0420
PMID:31990666
Abstract

Equine placentitis is associated with alterations in maternal peripheral steroid concentrations, which could negatively affect pregnancy outcome. This study aimed to elucidate the molecular mechanisms related to steroidogenesis and steroid-receptor signaling in the equine placenta during acute placentitis. Chorioallantois (CA) and endometrial (EN) samples were collected from mares with experimentally induced placentitis (n = 4) and un-inoculated gestationally age-matched mares (control group; n = 4). The mRNA expression of genes coding for steroidogenic enzymes (3βHSD, CYP11A1, CYP17A1, CYP19A1, SRD5A1, and AKR1C23) was evaluated using qRT-PCR. The concentration of these enzyme-dependent steroids (P5, P4, 5αDHP, 3αDHP, 20αDHP, 3β-20αDHP, 17OH-P, DHEA, A4, and estrone) was assessed using liquid chromatography-tandem mass spectrometry in both maternal circulation and placental tissue. Both SRD5A1 and AKR1C23, which encode for the key progesterone metabolizing enzymes, were downregulated (P < 0.05) in CA from the placentitis group compared to controls, and this downregulation was associated with a decline in tissue concentrations of 5αDHP (P < 0.05), 3αDHP (P < 0.05), and 3β-20αDHP (P = 0.052). In the EN, AKR1C23 was also downregulated in the placentitis group compared to controls, and this downregulation was associated with a decline in EN concentrations of 3αDHP (P < 0.01) and 20αDHP (P < 0.05). Moreover, CA expression of CYP19A1 tended to be lower in the placentitis group, and this reduction was associated with lower (P = 0.057) concentrations of estrone in CA. Moreover, ESR1 (steroid receptors) gene expression was downregulated (P = 0.057) in CA from placentitis mares. In conclusion, acute equine placentitis is associated with a local withdrawal of progestins in the placenta and tended to be accompanied with estrogen withdrawals in CA.

摘要

马属动物胎膜炎与母体外周类固醇浓度的改变有关,这可能会对妊娠结局产生负面影响。本研究旨在阐明急性胎膜炎时马属动物胎盘类固醇生成和类固醇受体信号转导相关的分子机制。从患有实验性胎膜炎的母马(n = 4)和未接种的同期妊娠母马(对照组;n = 4)的绒毛膜-卵黄囊(CA)和子宫内膜(EN)样本中收集了 mRNA 表达的基因编码类固醇生成酶(3βHSD、CYP11A1、CYP17A1、CYP19A1、SRD5A1 和 AKR1C23),并使用 qRT-PCR 进行评估。使用液相色谱-串联质谱法在母马循环和胎盘组织中评估这些酶依赖性类固醇(P5、P4、5αDHP、3αDHP、20αDHP、3β-20αDHP、17OH-P、DHEA、A4 和雌酮)的浓度。与对照组相比,胎膜炎组 CA 中的关键孕酮代谢酶编码基因 SRD5A1 和 AKR1C23 下调(P < 0.05),这种下调与 5αDHP(P < 0.05)、3αDHP(P < 0.05)和 3β-20αDHP(P = 0.052)组织浓度下降有关。在 EN 中,与对照组相比,胎膜炎组的 AKR1C23 也下调,这种下调与 3αDHP(P < 0.01)和 20αDHP(P < 0.05)的 EN 浓度下降有关。此外,CA 中 CYP19A1 的表达在胎膜炎组中趋于降低,这种减少与 CA 中雌酮浓度降低有关(P = 0.057)。此外,CA 中类固醇受体 ESR1 的基因表达下调(P = 0.057)。总之,急性马属动物胎膜炎与胎盘内孕激素的局部撤退有关,并且在 CA 中往往伴随着雌激素撤退。

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