Abstract

BackgroundProstate androgen-regulated mucin-like protein 1 (PARM1) is a pro-proliferative and anti-apoptotic glycoprotein involved in the endoplasmic reticulum (ER) stress response. A single nucleotide polymorphism in the coding region of PARM1 has been associated with competence of bovine embryos to develop to the blastocyst stage. Here we tested the importance of PARM1 for development by evaluating consequences of reducing PARM1 mRNA abundance on embryonic development and differentiation, gene expression and resistance to ER stress.ResultsKnockdown of PARM1 using an anti-PARM1 GapmeR did not affect competence of embryos to develop into blastocysts but decreased the number of trophectoderm (TE) cells in the blastocyst and tended to increase the number of cells in the blastocyst inner cell mass (ICM). Treatment of embryos with anti-PARM1 GapmeR affected expression of 4 and 3 of 90 genes evaluated at the compact-morula and blastocyst stage of development at days 5.5 and 7.5 after fertilization, respectively. In morulae, treatment increased expression of DAB2, INADL, and STAT3 and decreased expression of CCR2. At the blastocyst stage, knockdown of PARM1 increased expression of PECAM and TEAD4 and decreased expression of CCR7. The potential role of PARM1 in ER stress response was determined by evaluating effects of knockdown of PARM1 on development of embryos after exposure to heat shock or tunicamycin and on expression of ATF6, DDIT3 and EIF2AK3 at the compact morula and blastocyst stages. Both heat shock and tunicamycin reduced the percent of embryos becoming a blastocyst but response was unaffected by PARM1 knockdown. Similarly, there was no effect of knockdown on steady-state amounts of ATF6, DDIT3 or EIF2AK3.ConclusionPARM1 participates in formation of TE and ICM cells in early embryonic development but there is no evidence for the role of PARM1 in the ER stress response.

Highlights

  • Prostate androgen-regulated mucin-like protein 1 (PARM1) is a pro-proliferative and anti-apoptotic glycoprotein involved in the endoplasmic reticulum (ER) stress response

  • There was an association between a non-synonoymous single nucleotide polymoprhism (SNP) in the coding region of PARM1 with competence of cultured bovine embryos to develop to the blastocyst stage [7]; embryos sired by heterozygous bulls were

  • We evaluated whether reducing transcript abundance for PARM1 would alter expression of three genes involved in the ER stress response, namely ATF6, DDIT3 and EIF2AK3

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Summary

Introduction

Prostate androgen-regulated mucin-like protein 1 (PARM1) is a pro-proliferative and anti-apoptotic glycoprotein involved in the endoplasmic reticulum (ER) stress response. A single nucleotide polymorphism in the coding region of PARM1 has been associated with competence of bovine embryos to develop to the blastocyst stage. There was an association between a non-synonoymous single nucleotide polymoprhism (SNP) in the coding region of PARM1 with competence of cultured bovine embryos to develop to the blastocyst stage [7]; embryos sired by heterozygous bulls were. Zolini et al BMC Developmental Biology (2019) 19:15 more likely to become a blastocyst than embryos sired by bulls homozygous for either SNP. Actions on cardiomyocytes involve upregulation of expression of BMP2 and BMP4 [8] Both of these bone morphogenetic proteins can regulate expression of transcription factor genes involved in differentiation [10]. Inhibition of ER stress improved the proportion of mouse and cattle embryos developing to the blastocyst stage [12, 13]

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