BACKGROUND 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. 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. RESULTS Knockdown 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. CONCLUSION PARM1 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.

中文翻译：

---

前列腺雄激素调节的粘蛋白样蛋白1在牛胚泡发育中的重要性。

背景技术前列腺雄激素调节的粘蛋白样蛋白1（PARM1）是一种参与内质网（ER）应激反应的促增殖和抗凋亡糖蛋白。PARM1编码区中的单核苷酸多态性已与牛胚胎发育到胚泡期的能力有关。在这里，我们通过评估减少PARM1 mRNA丰度对胚胎发育和分化，基因表达以及对内质网应激的抵抗力的后果，测试了PARM1对发育的重要性。结果使用抗PARM1 GapmeR敲低PARM1不会影响胚胎发育为胚泡的能力，但会减少胚泡中滋养外胚层（TE）细胞的数量，并倾向于增加胚泡内部细胞团（ICM）中的细胞数量。用抗PARM1 GapmeR处理胚胎会影响分别在受精后第5.5天和第7.5天在紧密mor和胚泡发育阶段评估的90个基因中的4个和3个基因的表达。在桑ula中，治疗增加了DAB2，INADL和STAT3的表达，并降低了CCR2的表达。在胚泡期，敲低PARM1会增加PECAM和TEAD4的表达，并降低CCR7的表达。通过评估PARM1的敲低对热休克或衣霉素暴露后的胚胎发育以及紧实桑ula和胚泡期ATF6，DDIT3和EIF2AK3表达的影响，确定了PARM1在内质网应激反应中的潜在作用。热休克和衣霉素均降低了成为胚泡的胚的百分比，但应答不受PARM1敲低的影响。同样，击倒对ATF6，DDIT3或EIF2AK3的稳态量没有影响。结论PARM1在早期胚胎发育中参与TE和ICM细胞的形成，但没有证据表明PARM1在内质网应激反应中的作用。