PPAR-gamma influences developmental competence and trophectoderm lineage specification in bovine embryos

IF 3.7 3区生物学 Q1 DEVELOPMENTAL BIOLOGY Reproduction Pub Date : 2024-02-01 DOI:10.1530/rep-23-0334

Maura S McGraw, Sandeep K Rajput, Bradford W Daigneault

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In brief

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.

Abstract

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.

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PPAR-gamma 影响牛胚胎的发育能力和滋养层系谱分化

摘要过氧化物酶体增殖体激活受体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。摘要过氧化物酶体增殖激活受体γ（PPARG）是新陈代谢的关键调控因子，其保守作用对胎盘功能不可或缺，这表明它在植入前胚胎发育中发挥着以前未被发现的重要作用。在此，我们报告了牛 PPARG 的功能特征，揭示了其在胚胎发育第 6 天开始的核表达和无处不在的表达模式。与 PPARG- 胚胎相比，第 6 天 PPARG+ 胚胎的总细胞数较少，滋养层细胞比例较低（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）。暴露于罗格列酮的第 7.5 天（D7.5）发育延迟胚胎表达的对胎盘发育和细胞系形成很重要的关键基因（CDX2、RXRB、SP1、TFAP2C、SIRT1 和 PTEN）的转录本丰度较低。相反，Ros 不会改变 D7.5 囊胚的转录本丰度，但 GW 处理会降低 RXRA、RXRB、SP1 和 NFKB1 的表达。敲除胚胎 PPARG 不会改变囊胚的形成和孵化能力，但会减少 D7.5 囊胚的细胞总数。PPARG 的靶向药理学扰乱和胚胎基因敲除后，胚胎发育反应和受影响途径的减少表明了母体和胚胎的作用。这些数据揭示了 PPARG 在植入前胚胎发育、细胞系形成和与胎盘功能相关的转录本调控中的作用。

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来源期刊

Reproduction 生物-发育生物学

CiteScore

7.40

自引率

2.60%

发文量

199

审稿时长

4-8 weeks

期刊介绍： Reproduction is the official journal of the Society of Reproduction and Fertility (SRF). It was formed in 2001 when the Society merged its two journals, the Journal of Reproduction and Fertility and Reviews of Reproduction. Reproduction publishes original research articles and topical reviews on the subject of reproductive and developmental biology, and reproductive medicine. The journal will consider publication of high-quality meta-analyses; these should be submitted to the research papers category. The journal considers studies in humans and all animal species, and will publish clinical studies if they advance our understanding of the underlying causes and/or mechanisms of disease. Scientific excellence and broad interest to our readership are the most important criteria during the peer review process. The journal publishes articles that make a clear advance in the field, whether of mechanistic, descriptive or technical focus. Articles that substantiate new or controversial reports are welcomed if they are noteworthy and advance the field. Topics include, but are not limited to, reproductive immunology, reproductive toxicology, stem cells, environmental effects on reproductive potential and health (eg obesity), extracellular vesicles, fertility preservation and epigenetic effects on reproductive and developmental processes.