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犬胎盘前列腺素的生物合成和降解:前列腺素 F2α 合酶 (PGFS, AKR1C3) 和 15-羟前列腺素脱氢酶 (HPGD) 表达和功能的产前变化。

Biosynthesis and degradation of canine placental prostaglandins: prepartum changes in expression and function of prostaglandin F2α-synthase (PGFS, AKR1C3) and 15-hydroxyprostaglandin dehydrogenase (HPGD).

机构信息

Institute of Veterinary Anatomy, Vetsuisse Faculty, University of Zurich, Winterthurerstrasse 260, Zurich, Switzerland.

出版信息

Biol Reprod. 2013 Jul 5;89(1):2. doi: 10.1095/biolreprod.113.109918. Print 2013 Jul.

DOI:10.1095/biolreprod.113.109918
PMID:23677986
Abstract

There is no distinct explanation of the mechanism for the prepartal prostaglandin F2alpha (PGF2alpha) increase in pregnant dogs. Although the PGF2alpha-synthase (PGFS [AKR1C3]) mRNA expression and localization profiles have been previously investigated in canine utero/placental compartments, the availability and biochemical activity of the PGFS (AKR1C3) protein remain unknown. In order to better understand the regulation of canine uterine PGF2alpha availability and eventual prepartum release in luteolytic amounts in dogs, canine-specific PGFS (AKR1C3) and 15-hydroxyprostaglandin dehydrogenase (HPGD) antibodies were generated and used to characterize the expression, cellular localization, and biochemical properties of PGFS (AKR1C3) and HPGD in the utero/placental compartments and corpus luteum throughout pregnancy and at prepartum luteolysis. PGFS (AKR1C3) expression was weak or absent in luteal samples. Uterine PGFS (AKR1C3) was up-regulated postimplantation and declined prepartum. The utero/placental expression of PGFS (AKR1C3) was identified in the superficial uterine glands throughout gestation and in the trophoblast cells within the feto-maternal contact zone during placentation, suggesting a possible role for PGFS (AKR1C3) in the trophoblast invasion. Utero-placental HPGD was up-regulated until postimplantation, lower at midgestation, and greatly suppressed at prepartum. Expression was routinely identified in the endometrial surface and glandular epithelia, and positive signals were also observed in the trophoblast cells at the feto-maternal contact zone. The biochemical activity of recombinant PGFS (AKR1C3) and HPGD was confirmed after its expression in a heterologous system. The colocalization of HPGD with PGFS (AKR1C3) expression suggests a modulatory role for HPGD as a gatekeeper of the supply of prostaglandin in the pregnant canine uterus.

摘要

在怀孕的犬中,前列腺素 F2alpha(PGF2alpha)增加的机制尚无明确解释。尽管犬的子宫/胎盘隔室中已经研究了前列腺素 F2alpha 合酶(PGFS [AKR1C3])mRNA 的表达和定位谱,但 PGFS(AKR1C3)蛋白的可用性和生化活性仍不清楚。为了更好地理解犬子宫 PGF2alpha 可用性的调节以及最终在犬黄体溶解期间以分娩前的量释放,产生了犬特异性 PGFS(AKR1C3)和 15-羟前列腺素脱氢酶(HPGD)抗体,并用于在整个妊娠期间和分娩前黄体溶解时在子宫/胎盘隔室和黄体中表征 PGFS(AKR1C3)和 HPGD 的表达、细胞定位和生化特性。黄体样品中 PGFS(AKR1C3)的表达微弱或不存在。植入后,子宫 PGFS(AKR1C3)上调,并在分娩前下降。在整个妊娠期间,PGFS(AKR1C3)在子宫表面腺中,以及在胎盘形成时胎-母体接触区的滋养层细胞中鉴定出子宫/胎盘 PGFS(AKR1C3)的表达,表明 PGFS(AKR1C3)在滋养层细胞侵袭中可能发挥作用。子宫胎盘 HPGD 在植入后上调,妊娠中期降低,分娩前大大抑制。在子宫内膜表面和腺上皮中常规鉴定到表达,并且在胎-母体接触区的滋养层细胞中也观察到阳性信号。在异源系统中表达后,确认了重组 PGFS(AKR1C3)和 HPGD 的生化活性。HPGD 与 PGFS(AKR1C3)表达的共定位表明 HPGD 作为犬怀孕子宫中前列腺素供应的调节因子发挥作用。

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