Department of Animal Sciences, University of Florida, Gainesville, Florida, USA.
Genus PLC, DeForest, Wisconsin, USA.
Reproduction. 2024 Jan 31;167(2). doi: 10.1530/REP-23-0334. Print 2024 Feb 1.
Peroxisome proliferator-activated receptor gamma (PPARG) is a critical regulator of placental function, but earlier roles in preimplantation embryo development and embryonic origins of placental formation have not been established. Results herein demonstrate that PPARG responds to pharmacologic stimulation in the bovine preimplantation embryo and influences blastocyst development, cell lineage specification, and transcripts important for placental function.
Peroxisome proliferator-activated receptor gamma (PPARG) is a key regulator of metabolism with conserved roles that are indispensable for placental function, suggesting previously unidentified and important roles in preimplantation embryo development. Herein, we report the functional characterization of bovine PPARG to reveal expression beginning on D6 of development with nuclear and ubiquitous patterns. Day 6 PPARG+ embryos have fewer total cells and a lower proportion of trophectoderm cells compared to PPARG- embryos (P < 0.05). Coculture with a PPARG agonist, rosiglitazone (Ros), or antagonist GW9662 (GW), decreases blastocyst development (P < 0.01). Day 7.5 (D7.5) developmentally delayed embryos exposed to Ros express lower transcript abundance of key genes important for placental development and cell lineage formation (CDX2, RXRB, SP1, TFAP2C, SIRT1, and PTEN). In contrast, Ros does not alter transcript abundance in D7.5 blastocysts, but GW treatment lowers RXRA, RXRB, SP1, and NFKB1 expression. Knockout of embryonic PPARG does not alter blastocyst formation and hatching ability but decreases total cell number in D7.5 blastocysts. The decreased embryo development response and affected pathways following targeted pharmacological perturbation vs embryonic knockout of PPARG suggest roles of both maternal and embryonic origins. These data reveal regulatory contributions of PPARG in preimplantation embryo development, cell lineage formation, and regulation of transcripts associated with placental function.
过氧化物酶体增殖物激活受体γ（PPARG）是胎盘功能的关键调节因子，但它在植入前胚胎发育和胎盘形成的胚胎起源中的早期作用尚未确定。本文的结果表明，PPARG 对牛植入前胚胎的药物刺激有反应，并影响囊胚发育、细胞谱系特化以及与胎盘功能相关的重要转录本。
过氧化物酶体增殖物激活受体γ（PPARG）是代谢的关键调节剂，具有保守作用，对胎盘功能是不可或缺的，这表明其在植入前胚胎发育中具有以前未被识别的重要作用。在此，我们对牛 PPARG 的功能进行了表征，结果显示其表达始于发育的第 6 天，具有核和普遍的模式。与 PPARG-胚胎相比，第 6 天 PPARG+胚胎的总细胞数更少，滋养外胚层细胞的比例更低（P < 0.05）。与 PPARG 激动剂罗格列酮（Ros）或拮抗剂 GW9662（GW）共培养会降低囊胚的发育（P < 0.01）。暴露于 Ros 的第 7.5 天（D7.5）发育延迟的胚胎表达的与胎盘发育和细胞谱系形成相关的关键基因的转录本丰度较低（CDX2、RXRB、SP1、TFAP2C、SIRT1 和 PTEN）。相反，Ros 不会改变 D7.5 囊胚中的转录本丰度，但 GW 处理会降低 RXRA、RXRB、SP1 和 NFKB1 的表达。胚胎 PPARG 的敲除不会改变囊胚的形成和孵化能力，但会降低 D7.5 囊胚中的总细胞数。靶向药物干扰与胚胎敲除 PPARG 后胚胎发育反应和受影响的途径不同，表明母体和胚胎起源都有作用。这些数据揭示了 PPARG 在植入前胚胎发育、细胞谱系形成以及与胎盘功能相关的转录本调控中的作用。
