Department of Pediatrics and Adolescent Medicine, University of Erlangen-Nürnberg, Erlangen, Germany.
Reprod Biol Endocrinol. 2012 Sep 12;10:80. doi: 10.1186/1477-7827-10-80.
The placental syncytiotrophoblast is the major source of maternal plasma corticotropin-releasing hormone (CRH) in the second half of pregnancy. Placental CRH exerts multiple functions in the maternal organism: It induces the adrenal secretion of cortisol via the stimulation of adrenocorticotropic hormone, regulates the timing of birth via its actions in the myometrium and inhibits the invasion of extravillous trophoblast cells in vitro. However, the auto- and paracrine actions of CRH on the syncytiotrophoblast itself are unknown. Intrauterine growth restriction (IUGR) is accompanied by an increase in placental CRH, which could be of pathophysiological relevance for the dysregulation in syncytialisation seen in IUGR placentas.
We aimed to determine the effect of CRH on isolated primary trophoblastic cells in vitro. After CRH stimulation the trophoblast syncytialisation rate was monitored via syncytin-1 gene expression and beta-hCG (beta-human chorionic gonadotropine) ELISA in culture supernatant. The expression of the IUGR marker genes leptin and 11beta-hydroxysteroid dehydrogenase 2 (11beta-HSD2) was measured continuously over a period of 72 h. We hypothesized that CRH might attenuate syncytialisation, induce leptin, and reduce 11beta-HSD2 expression in primary villous trophoblasts, which are known features of IUGR.
CRH did not influence the differentiation of isolated trophoblasts into functional syncytium as determined by beta-hCG secretion, albeit inducing syncytin-1 expression. Following syncytialisation, CRH treatment significantly increased leptin and 11beta-HSD2 expression, as well as leptin secretion into culture supernatant after 48 h.
The relevance of CRH for placental physiology is underlined by the present in vitro study. The induction of leptin and 11beta-HSD2 in the syncytiotrophoblast by CRH might promote fetal nutrient supply and placental corticosteroid metabolism in the phase before labour induction.
胎盘合体滋养层是妊娠后半期母体血浆促肾上腺皮质激素释放激素（CRH）的主要来源。胎盘 CRH 在母体组织中发挥多种功能：通过刺激促肾上腺皮质激素诱导肾上腺分泌皮质醇，通过在子宫肌层中的作用调节分娩时间，并抑制体外绒毛外滋养层细胞的浸润。然而，CRH 对合体滋养层自身的自分泌和旁分泌作用尚不清楚。宫内生长受限（IUGR）伴随着胎盘 CRH 的增加，这可能与 IUGR 胎盘合体滋养层中合胞体化失调的病理生理相关。
我们旨在确定 CRH 对离体滋养细胞的影响。在 CRH 刺激后，通过同步素-1 基因表达和培养上清液中的β-hCG（β-人绒毛膜促性腺激素）ELISA 监测滋养层合胞体化率。连续测量 IUGR 标志物基因瘦素和 11β-羟类固醇脱氢酶 2（11β-HSD2）的表达 72 小时。我们假设 CRH 可能会减弱合胞体化，诱导瘦素表达，并降低已知 IUGR 特征的原代绒毛滋养细胞中的 11β-HSD2 表达。
CRH 并未影响分离的滋养细胞分化为功能性合胞体，尽管诱导了同步素-1 的表达。合胞体化后，CRH 处理显著增加了瘦素和 11β-HSD2 的表达，以及 48 小时后培养上清液中瘦素的分泌。
本体外研究强调了 CRH 对胎盘生理学的重要性。CRH 在合体滋养层中诱导瘦素和 11β-HSD2 的表达可能会促进胎儿在分娩诱导前的营养供应和胎盘皮质醇代谢。
