Effects of palmitic acid on localization of embryo cell fate and blastocyst formation gene products

Abstract

As obese and overweight patients commonly display hyperlipidemia, and are increasingly accessing fertility clinics for their conception needs, our studies are directed at understanding the effects of hyperlipidemia on early pregnancy. We have focused on investigating palmitic acid (PA) and oleic acid (OA) treatment alone and in combination from the mouse two-cell stage as a model for understanding their effects on the mammalian preimplantation embryo. We recently reported that PA exerts a negative effect on mouse two-cell progression to the blastocyst stage, whereas OA co-treatment reverses that negative effect. In the present study, we hypothesized that PA treatment of mouse embryos would disrupt proper localization of cell fate determining and blastocyst formation gene products, and that co-treatment with oleic acid would reverse these effects. Our results demonstrate that PA treatment significantly (p<0.05) reduces blastocyst development and cell number but did not prevent nuclear localization of YAP in outer cells. PA treatment significantly reduced the number of OCT4+ and CDX2+ nuclei. PA treated embryos had lower expression of blastocyst formation proteins (E-cadherin, ZO-1 and Na/K-ATPase alpha1 subunit). Importantly, co-treatment of embryos with OA reversed PA-induced effects on blastocyst development and increased ICM and TE cell numbers and expression of blastocyst formation proteins. Our findings demonstrate that PA treatment does not impede cell fate gene localization but does disrupt proper blastocyst formation gene localization during mouse preimplantation development. OA treatment is protective and reverses PA’s detrimental effects. The results advance our understanding of the impact of FFA exposure on mammalian preimplantation development.

Fatty acid supplementation during warming improves pregnancy outcomes after frozen blastocyst transfers: a propensity score-matched study

“…It has been established that the exogenous supply of FAs in culture medium can affect reproductive potential, such as oocyte maturation, cryopreservation, oxidative stress, and cellular signaling, in various species 35 – 37 . Furthermore, an excessive amount of FAs, especially saturated FAs, reportedly resulted in reticulum stress, lower fertilization and embryo development rates, and caused irreversible damage to fetal growth and offspring health 38 – 43 . However, the concentration of FAs in the warming solution used in this study was much lower (approximately 1/1000) than those in previous studies that demonstrated the detrimental effects of FAs.…”