Lysophosphatidic Acid Signaling in Late Cleavage and Blastocyst Stage Bovine Embryos

Abstract

Lysophosphatidic acid (LPA) is a known cell signaling lipid mediator in reproductive tissues. In the cow, LPA is involved in luteal and early pregnancy maintenance. Here, we evaluated the presence and role of LPA in bovine early embryonic development. In relevant aspects, bovine embryos reflect more closely the scenario occurring in human embryos than the mouse model. Transcription of mRNA and protein expression of enzymes involved in LPA synthesis (ATX and cPLA2) and of LPA receptors (LPAR1–4) were detected in Days 5 and 8 in vitro produced embryos. Embryonic LPA production into culture medium was also detected at both stages of development. Supplementation of culture medium with LPA (10−5 M) between Days 2 and 8 had no effect on embryo yield and quality and on blastocyst relative mRNA abundance of genes involved in prostaglandin synthesis (PTGS2, PGES, and PGFS) and steroidogenesis (3β HSD). However, LPA treatment affected transcription levels of embryo quality markers, decreasing BAX (apoptotic) and increasing BCL2 (antiapoptotic) and IGF2R (growth marker) gene transcription levels. Blastocyst transcription of OCT4 (pluripotency marker) was not affected by LPA stimulation. In conclusion, LPA is an early bovine embryonic autocrine/paracrine signaling mediator, and LPA action may be relevant in early embryo-maternal interactions leading to embryonic survival.

Early development of porcine parthenogenetic embryos and reduced expression of primed pluripotent marker genes under the effect of lysophosphatidic acid

“…This result, significantly increasing OCT4 expression, was consistent with the results of the study conducted by Torres et al. () , with bovine. Many studies have shown that endogenous transcription factor OCT4 was the core factor in regulating pluripotency.…”

Cytosolic phospholipase A2: physiological function and role in disease

“…Several pathways for the synthesis of LPA have been described ( 215,216 ). Although there is correlative data that cPLA 2 ␣ may play a role in the initial production of lysophospholipids that are metabolized to LPA by autotaxin, there is as yet little defi nite data to support a role for cPLA 2 ␣ in LPA production ( 217,218 ).…”

Autocrine embryotropins revisited: how do embryos communicate with each otherin vitrowhen cultured in groups?

“…Recently, mRNA transcripts and protein expression of enzymes involved in LPA synthesis and LPA receptors were identified in late‐stage cleavage bovine embryos and blastocysts. LPA has been detected in bovine embryo‐conditioned medium (Torres et al , ). Addition of LPA to the culture medium increased blastocyst development of murine embryos (Kobayashi et al , ), but not of bovine embryos, although transcription levels of embryo quality markers were certainly affected in the latter; e.g.…”

“…Addition of LPA to the culture medium increased blastocyst development of murine embryos (Kobayashi et al , ), but not of bovine embryos, although transcription levels of embryo quality markers were certainly affected in the latter; e.g. Bcl2‐Associated X ( BAX ) (apoptotic) decreased while B‐cell lymphoma 2 ( BCL2 ) (anti‐apoptotic) and insulin‐like growth factor 2 receptor ( IGF2R ) (growth marker) increased (Torres et al , ). Another bioactive cell membrane metabolite is sphingosine‐1 phosphate (S1P), a potent anti‐apoptotic substance that acts by binding a family of five G‐protein‐coupled receptors.…”