2. Academic Validation
  3. TGF-β3 Promotes Trophoblast Development in Sheep Embryos via ACSS2-Dependent Permissive Lipid Metabolism

TGF-β3 Promotes Trophoblast Development in Sheep Embryos via ACSS2-Dependent Permissive Lipid Metabolism

  • Biol Reprod. 2025 Oct 1:ioaf220. doi: 10.1093/biolre/ioaf220.
Francesca Boffa 1,  Marika Domenicone 1,  Margherita Moncada 1,  Martina Lo Sterzo 1,  Luca Palazzese 1,  Aurora Scuderi 1,  Emanuele Capra 2,  Barbari Lazzari 2,  Luca Valbonetti 3,  Luisa Gioia 3,  Ramiro Alberio 4,  Domenico Iuso 1,  Pasqualino Loi 1,  Marta Czernik 1
Affiliations

Affiliations

  • 1 University of Teramo, Department of Veterinary Medicine, 64100 Teramo, Italy.
  • 2 CNR-IBBA, Institute of Agricultural Biology and Biotechnology, National Research Council, Via Einstein, Lodi 26900, Italy.
  • 3 Department of Bioscience and Technology for Food, Agriculture and Environment, University of Teramo, Teramo, 64100, Italy.
  • 4 School of Biosciences, University of Nottingham, Sutton Bonington Campus, Nottingham, LE12 5RD, UK.
PMID: 41031631 DOI: 10.1093/biolre/ioaf220
Abstract

Transforming growth factor-beta (TGF-β) supports the in vitro maintenance of embryonic and trophoblast stem cells. Here, we demonstrated that, in a sheep embryo model, the transition from morula to blastocyst is positively regulated by TGF-β3, primarily through its promotion of trophoblast development. Our results indicate that morulae treated with TGF-β3 develop at a higher rate into blastocysts, characterized by an expanded trophoblast layer marked by CDX-2 expression. In blastocysts, TGF-β3 mediates transcriptional activation of genes involved in cell adhesion and lipid metabolism pathways, leading to remarkable in vitro outgrowth expansion and a substantial increase in trophoblast lipid droplet content. Functional analysis reveals that the positive effects of TGF-β3 are mitigated by inhibition of Acetyl-CoA synthetase Short-Chain Family Member 2 (ACSS2), a key enzyme upregulated by TGF-β3 and a promoter of de novo lipogenesis. These findings suggest that TGF-β3 modulates lipid metabolism during blastocyst formation and may play a potential role in regulating implantation and placental development.

Keywords

Blastocyst; In vitro; Ovine; TGF-β3; Trophoblast.

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