Impact of Chorionic Somatomammotropin In Vivo RNA Interference Phenotype on Uteroplacental Expression of the IGF Axis.
Impact of Chorionic Somatomammotropin In Vivo RNA Interference Phenotype on Uteroplacental Expression of the IGF Axis.
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DOI：
10.3390/life13061261
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发表时间：
2023-05-26
期刊：
影响因子：
3.2
通讯作者：
Anthony, Russell V.
中科院分区：
文献类型：
--
作者：
Hord, Taylor K.;Tanner, Amelia R.;Kennedy, Victoria C.;Lynch, Cameron S.;Winger, Quinton A.;Rozance, Paul J.;Anthony, Russell V.
虽然胎儿生长取决于许多因素，但最佳胎盘功能是正常妊娠结局的先决条件。大多数胎儿生长受限（FGR）妊娠是由胎盘功能不全（PI）引起的。胰岛素样生长因子（IGF 1和IGF 2）刺激胎儿生长和胎盘发育和功能。以前，我们证明，在体内RNA干扰（RNAi）的胎盘激素，绒毛膜生长催乳素（CSH），导致两种表型。一种表型表现出显著的胎盘和胎儿生长受限（PI-FGR），胎盘营养转运受损，脐胰岛素和IGF 1显著降低。另一种表型在胎盘或胎儿生长（非FGR）方面未表现出统计学显著性变化。我们的目的是通过确定CSH RNAi对胎盘（母体肉阜和胎儿子叶）IGF轴表达的影响来进一步表征这两种表型。在胚胎移植到同步化受体母羊中之前，用表达非靶向序列（NTS RNAi）对照或CSH特异性shRNA（CSH RNAi）的慢病毒感染孵化囊胚（妊娠9天，dGA）的滋养外胚层。在125 dGA时，孕妇安装血管导管进行稳态代谢研究。测定营养吸收，并在尸检时收获组织。在CSH RNAi非FGR和PI-FGR妊娠中，子宫血流量显著减少（p ≤ 0.05），而在CSH RNAi PI-FGR妊娠中，脐血流量（p ≤ 0.01）、子宫和脐葡萄糖和氧摄取（p ≤ 0.05）以及胰岛素和IGF 1的脐浓度（p ≤ 0.05）减少。在CSH RNAi PI-FGR妊娠中，胎儿子叶IGF 1 mRNA浓度降低（p ≤ 0.05），而在非FGR妊娠中，母体肉阜和胎盘组织中的IGF 1和IGF 2 mRNA浓度均不受影响。胎儿子叶IGF 1 R和IGF 2 R mRNA浓度不受任一表型的影响，但在CSH RNAi PI-FGR妊娠的母体阜中IGF 2 R增加（p ≤ 0.01）。对于IGF结合蛋白（IGFBP 1、IGFBP 2、IGFBP 3），仅IGFBP 2 mRNA浓度受到影响，在CSH RNAi非FGR妊娠的胎儿子叶（p ≤ 0.01）和母体肉阜（p = 0.08）中IGFBP 2 mRNA均升高。这些数据支持IGF 1在胎盘生长和功能中的重要性，但也可能暗示IGFBP 2在非FGR妊娠中挽救胎盘生长。
While fetal growth is dependent on many factors, optimal placental function is a prerequisite for a normal pregnancy outcome. The majority of fetal growth-restricted (FGR) pregnancies result from placental insufficiency (PI). The insulin-like growth factors (IGF1 and IGF2) stimulate fetal growth and placental development and function. Previously, we demonstrated that in vivo RNA interference (RNAi) of the placental hormone, chorionic somatomammotropin (CSH), resulted in two phenotypes. One phenotype exhibits significant placental and fetal growth restriction (PI-FGR), impaired placental nutrient transport, and significant reductions in umbilical insulin and IGF1. The other phenotype does not exhibit statistically significant changes in placental or fetal growth (non-FGR). It was our objective to further characterize these two phenotypes by determining the impact of CSH RNAi on the placental (maternal caruncle and fetal cotyledon) expression of the IGF axis. The trophectoderm of hatched blastocysts (9 days of gestation, dGA) were infected with a lentivirus expressing either a non-targeting sequence (NTS RNAi) control or CSH-specific shRNA (CSH RNAi) prior to embryo transfer into synchronized recipient ewes. At ≈125 dGA, pregnancies were fitted with vascular catheters to undergo steady-state metabolic studies. Nutrient uptakes were determined, and tissues were harvested at necropsy. In both CSH RNAi non-FGR and PI-FGR pregnancies, uterine blood flow was significantly reduced (p ≤ 0.05), while umbilical blood flow (p ≤ 0.01), both uterine and umbilical glucose and oxygen uptakes (p ≤ 0.05), and umbilical concentrations of insulin and IGF1 (p ≤ 0.05) were reduced in CSH RNAi PI-FGR pregnancies. Fetal cotyledon IGF1 mRNA concentration was reduced (p ≤ 0.05) in CSH RNAi PI-FGR pregnancies, whereas neither IGF1 nor IGF2 mRNA concentrations were impacted in the maternal caruncles, and either placental tissue in the non-FGR pregnancies. Fetal cotyledon IGF1R and IGF2R mRNA concentrations were not impacted for either phenotype, yet IGF2R was increased (p ≤ 0.01) in the maternal caruncles of CSH RNAi PI-FGR pregnancies. For the IGF binding proteins (IGFBP1, IGFBP2, IGFBP3), only IGFBP2 mRNA concentrations were impacted, with elevated IGFBP2 mRNA in both the fetal cotyledon (p ≤ 0.01) and maternal caruncle (p = 0.08) of CSH RNAi non-FGR pregnancies. These data support the importance of IGF1 in placental growth and function but may also implicate IGFBP2 in salvaging placental growth in non-FGR pregnancies.
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影响因子：
3.5
作者：
Höflich, A;Lahm, H;Wolf, E
通讯作者：
Wolf, E
DOI：
10.1113/jp281288
发表时间：
2021-07
期刊：
The Journal of physiology
影响因子：
--
作者：
Cilvik SN;Wesolowski SR;Anthony RV;Brown LD;Rozance PJ
通讯作者：
Rozance PJ
DOI：
10.1530/joe-18-0093
发表时间：
2018-06
期刊：
The Journal of endocrinology
影响因子：
--
作者：
Jeckel KM;Boyarko AC;Bouma GJ;Winger QA;Anthony RV
通讯作者：
Anthony RV
影响因子：
64.5
作者：
BAKER, J;LIU, JP;EFSTRATIADIS, A
通讯作者：
EFSTRATIADIS, A
影响因子：
3.6
作者：
De Vrijer, Barbra;Davidsen, Meredith L.;Regnault, Timothy R. H.
通讯作者：
Regnault, Timothy R. H.