Lysophosphatidic Acid Signaling in Late Cleavage and Blastocyst Stage Bovine Embryos

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.

[1]  E. Sinderewicz,et al.  Influence of lysophosphatidic acid on estradiol production and follicle stimulating hormone action in bovine granulosa cells. , 2013, Reproductive biology.

[2]  E. Sinderewicz,et al.  Effects of lysophopatidic acid on tumor necrosis factor α and interferon γ action in the bovine corpus luteum , 2013, Molecular and Cellular Endocrinology.

[3]  Tristan Frum,et al.  Oct4 cell-autonomously promotes primitive endoderm development in the mouse blastocyst. , 2013, Developmental cell.

[4]  J. Saulnier-Blache,et al.  Which bovine endometrial cells are the source of and target for lysophosphatidic acid? , 2013, Reproductive biology.

[5]  L. Mateus,et al.  Embryo–luteal cells co-culture: an in vitro model to evaluate steroidogenic and prostanoid bovine early embryo–maternal interactions , 2013, In Vitro Cellular & Developmental Biology - Animal.

[6]  M. Gotoh,et al.  Protection of Neuroblastoma Neuro2A Cells from Hypoxia-Induced Apoptosis by Cyclic Phosphatidic Acid (cPA) , 2012, PloS one.

[7]  J. Saulnier-Blache,et al.  Lysophosphatidic acid action in the bovine corpus luteum -an in vitro study. , 2012, The Journal of reproduction and development.

[8]  K. Niakan,et al.  Human pre-implantation embryo development , 2012, Development.

[9]  E. Wolf,et al.  Cell Arrest and Cell Death in Mammalian Preimplantation Development: Lessons from the Bovine Model , 2011, PloS one.

[10]  J. de Vos,et al.  Involvement of BCL2 family members in the regulation of human oocyte and early embryo survival and death: gene expression and beyond. , 2011, Reproduction.

[11]  N. Samadi,et al.  Regulation of lysophosphatidate signaling by autotaxin and lipid phosphate phosphatases with respect to tumor progression, angiogenesis, metastasis and chemo-resistance. , 2011, Biochimie.

[12]  G. Tigyi Aiming drug discovery at lysophosphatidic acid targets , 2010, British journal of pharmacology.

[13]  D. Skarzynski,et al.  Lysophosphatidic acid action during early pregnancy in the cow: in vivo and in vitro studies. , 2010, The Journal of reproduction and development.

[14]  D. Tainturier,et al.  Effect of the association of IGF-I, IGF-II, bFGF, TGF-beta1, GM-CSF, and LIF on the development of bovine embryos produced in vitro. , 2010, Theriogenology.

[15]  J. Stevens,et al.  Abnormal levels of transcript abundance of developmentally important genes in various stages of preimplantation bovine somatic cell nuclear transfer embryos. , 2010, Cellular reprogramming.

[16]  J. Chun,et al.  Lysophosphatidic acid (LPA) signaling in vertebrate reproduction , 2010, Trends in Endocrinology & Metabolism.

[17]  D. Skarzynski,et al.  Lysophosphatic acid modulates prostaglandin secretion in the bovine endometrial cells differently on days 8-10 of the estrous cycle and early pregnancy. , 2009, The Journal of reproduction and development.

[18]  I. Woclawek-Potocka,et al.  Lysophosphatidic Acid Stimulates Prostaglandin E2 Production in Cultured Stromal Endometrial Cells Through LPA1 Receptor , 2009, Experimental biology and medicine.

[19]  B. Boyan,et al.  Lysophosphatidic acid signaling promotes proliferation, differentiation, and cell survival in rat growth plate chondrocytes. , 2009, Biochimica et biophysica acta.

[20]  T. Hla,et al.  Lysophospholipid receptors in vertebrate development, physiology, and pathology Published, JLR Papers in Press, December 8, 2008. , 2009, Journal of Lipid Research.

[21]  P. Robin,et al.  Lysophosphatidic acid signaling during embryo development in sheep: involvement in prostaglandin synthesis. , 2009, Endocrinology.

[22]  K. Okuda,et al.  Lysophosphatic acid modulates prostaglandin secretion in the bovine uterus. , 2009, Reproduction.

[23]  Mingoo Kim,et al.  Analysis of lysophosphatidic acid (LPA) receptor and LPA-induced endometrial prostaglandin-endoperoxide synthase 2 expression in the porcine uterus. , 2008, Endocrinology.

[24]  J. Aoki,et al.  Two pathways for lysophosphatidic acid production. , 2008, Biochimica et biophysica acta.

[25]  J. Chun,et al.  Biological roles of lysophospholipid receptors revealed by genetic null mice: an update. , 2008, Biochimica et biophysica acta.

[26]  X. Ye Lysophospholipid signaling in the function and pathology of the reproductive system. , 2008, Human reproduction update.

[27]  C. Mummery,et al.  Autotaxin, a Secreted Lysophospholipase D, Is Essential for Blood Vessel Formation during Development , 2006, Molecular and Cellular Biology.

[28]  Sheng Zhao,et al.  Comprehensive Algorithm for Quantitative Real-Time Polymerase Chain Reaction , 2005, J. Comput. Biol..

[29]  Claus Lindbjerg Andersen,et al.  Normalization of Real-Time Quantitative Reverse Transcription-PCR Data: A Model-Based Variance Estimation Approach to Identify Genes Suited for Normalization, Applied to Bladder and Colon Cancer Data Sets , 2004, Cancer Research.

[30]  D. Armant,et al.  Lysophosphatidic acid regulates murine blastocyst development by transactivation of receptors for heparin-binding EGF-like growth factor. , 2004, Experimental cell research.

[31]  J. Southgate,et al.  Regulation of apoptosis in the bovine blastocyst by insulin and the insulin‐like growth factor (IGF) superfamily , 2002, Molecular Reproduction and Development.

[32]  R. Rajamahendran,et al.  Expression of Bcl-2 and Bax proteins in relation to quality of bovine oocytes and embryos produced in vitro. , 2002, Animal reproduction science.

[33]  M. Markkula,et al.  Apoptosis and Cell Proliferation Potential of Bovine Embryos Stimulated with Insulin-Like Growth Factor I During In Vitro Maturation and Culture1 , 2002, Biology of reproduction.

[34]  C. Wrenzycki,et al.  Changes in the relative abundance of mRNA transcripts for insulin-like growth factor (IGF-I and IGF-II) ligands and their receptors (IGF-IR/IGF-IIR) in preimplantation bovine embryos derived from different in vitro systems. , 2001, Reproduction.

[35]  P. Valet,et al.  A simple and highly sensitive radioenzymatic assay for lysophosphatidic acid quantification. , 2000, Journal of lipid research.

[36]  A. Tokumura,et al.  Effect of lysophosphatidic acid on the ovum transport in mouse oviducts. , 1999, Life sciences.

[37]  E. Goetzl,et al.  Lysophosphatidic acid and sphingosine 1-phosphate protection of T cells from apoptosis in association with suppression of Bax. , 1999, Journal of immunology.

[38]  H. Schöler,et al.  Formation of Pluripotent Stem Cells in the Mammalian Embryo Depends on the POU Transcription Factor Oct4 , 1998, Cell.

[39]  S. M. Seidel,et al.  Manual of the International Embryo Transfer Society , 1998 .

[40]  Z. Rosenwaks,et al.  Expression of IGFs and Their Receptors Is a Potential Marker for Embryo Quality , 1997, American journal of reproductive immunology.

[41]  A. Tokumura,et al.  Effect of lysophosphatidic acid on the preimplantation development of mouse embryos , 1994, FEBS letters.

[42]  Kees Jalink,et al.  Lysophosphatidate-induced cell proliferation: Identification and dissection of signaling pathways mediated by G proteins , 1989, Cell.