Evidence of Placental Autophagy during Early Pregnancy after Transfer of In Vitro Produced (IVP) Sheep Embryos

PLoS One. 2016 Jun 21;11(6):e0157594. doi: 10.1371/journal.pone.0157594. eCollection 2016.

Abstract

Pregnancies obtained by Assisted Reproductive Technologies (ART) are associated with limited maternal nutrient uptake. Our previous studies shown that in vitro culture of sheep embryos is associated with vascularization defects in their placentae and consequent reduction of embryo growth. Autophagy is a pro-survival cellular mechanism triggered by nutrient insufficiency. Therefore, the goal of our present study was to determine if autophagy is involved in early placental development after transfer of in vitro produced (IVP) embryos. To do this, placentae obtained following transfer of IVP sheep embryos were compared with placentae obtained after natural mating (control-CTR). The placentae were collected on day 20 post-fertilization and post-mating, respectively, and were analyzed using molecular (qPCR), ultrastructural and histological/immunological approaches. Our results show drastically increased autophagy in IVP placentae: high levels of expression (p<0.05) of canonical markers of cellular autophagy and a high proportion of autophagic cells (35.08%; p<0.001) were observed. We conclude that high autophagic activity in IVP placentae can be a successful temporary counterbalance to the retarded vasculogenesis and the reduction of foetal growth observed in pregnancies after transfer of IVP embryos.

MeSH terms

  • Animals
  • Autophagy*
  • Biomarkers / metabolism
  • Embryo Transfer*
  • Embryo, Mammalian
  • Female
  • Fertilization in Vitro*
  • Mitochondria / ultrastructure
  • Placenta / pathology*
  • Pregnancy
  • Sheep / embryology*

Substances

  • Biomarkers

Grants and funding

The research leading to these results received funding from the European Union’s Horizon 2020 Research and Innovation Programme under grant agreement No. 692185 (Acronym ERAofART) to GEP and European Union Seventh Framework Programme for research, technological development and demonstration under grant agreement n° 312097 FECUND, and from MIUR/CNR Programme FIRB GA n° B81J12002520001 Acronym: GenHome. The authors PT, MC, AF, FZ, PL and GEP are participating in the COST action FA 1201 EPICONCEPT - Epigenetic and Periconception Environment.