The Ritchie Centre, Monash Institute of Medical Research, Clayton, Victoria, Australia.
Biol Reprod. 2013 Jan 31;88(1):26. doi: 10.1095/biolreprod.112.100644. Print 2013 Jan.
High levels of maternal glucocorticoids during pregnancy can alter the developmental trajectory of some fetal organs. These perturbations are often more profound for the male fetus and have been attributed to passage of glucocorticoids through the placenta. However, the effect of excess glucocorticoids on the placenta itself is less well understood and, particularly, whether this is affected by fetal sex. Expression of genes involved in placental patterning, apoptosis, and nutrient transfer, along with their response to maternal administration of dexamethasone (DEX), has previously been shown to be dependent on fetal sex in the spiny mouse. Here we describe the placental spatiotemporal expression of genes important for branching morphogenesis (WNT4, BMP4, GREM1, TGFB1, KDR, VEGFA). Furthermore, we report that compared to TGFB1 expression in the female labyrinth, expression of TGFB1 in the male labyrinth was higher, and earlier peaks in expression levels of VEGFA (Day 19 placenta [male] vs. Day 37 labyrinth [female]) and KDR (Day 19 placenta [male] vs. Day 20 labyrinth [female]) were observed. Administration of DEX to pregnant dams for 60 h commencing at mid-gestation caused significantly different, sex-related changes in expression of genes that were constitutively different before DEX treatment (e.g., KDR, TGFB1) and those that were not (i.e., VEGFA, WNT4). Similarly, some genes which displayed similar expression profiles across gestation for both sexes also showed similar responses to DEX (e.g., BMP4), while others did not (i.e., GREM1). These results showed that constitutive and glucocorticoid-induced changes in expression of genes involved in branching morphogenesis may be influenced by fetal/placental sex and that fundamental differences exist between a male and female placenta.
怀孕期间母体糖皮质激素水平升高会改变某些胎儿器官的发育轨迹。这些干扰对雄性胎儿更为明显，这归因于糖皮质激素穿过胎盘。然而，过量的糖皮质激素对胎盘本身的影响则不太为人所理解，特别是这种影响是否受胎儿性别影响。以前已经表明，在多刺鼠中，参与胎盘模式形成、细胞凋亡和营养物质转移的基因的表达及其对母体地塞米松（DEX）处理的反应依赖于胎儿的性别。在这里，我们描述了对分支形态发生很重要的基因在胎盘中的时空表达（WNT4、BMP4、GREM1、TGFB1、KDR、VEGFA）。此外，我们报告说，与雌性迷路中的 TGFB1 表达相比，雄性迷路中的 TGFB1 表达更高，并且 VEGFA（雄性胎盘[第 19 天]与雌性迷路[第 37 天]）和 KDR（雄性胎盘[第 19 天]与雌性迷路[第 20 天]）的表达水平更早出现峰值。从中孕期开始，对怀孕的母鼠给予地塞米松处理 60 小时，导致在 DEX 处理前就存在差异的基因（例如 KDR、TGFB1）和那些没有差异的基因（即 VEGFA、WNT4）的表达发生了显著的、与性别相关的变化。同样，在两性中整个妊娠期的表达模式相似的一些基因也对地塞米松表现出相似的反应（例如 BMP4），而其他基因则没有（即 GREM1）。这些结果表明，参与分支形态发生的基因的组成性和糖皮质激素诱导的表达变化可能受到胎儿/胎盘性别的影响，并且雄性和雌性胎盘之间存在根本差异。
