Abu Dhabi Biotech Research Foundation, Seoul, Republic of Korea.
College of Veterinary Medicine, Chungbuk National University, Cheongju, South Korea.
PLoS One. 2020 Mar 17;15(3):e0230247. doi: 10.1371/journal.pone.0230247. eCollection 2020.
Granulocyte-colony stimulating factor (G-CSF), a pleiotropic cytokine, belongs to the hematopoietic growth factor family. Recent studies have reported that G-CSF is a predictive biomarker of oocyte and embryo developmental competence in humans. The aim of our study was to determine whether CSF3 and its receptor (CSF3R) were expressed in porcine maternal reproductive tissues (oviduct and uterus), cumulus cells, and embryos and to investigate the effects of human recombinant G-CSF (hrG-CSF) supplementation during in vitro culture (IVC) on the developmental competence of pre-implantation embryos. To do this, we first performed reverse-transcription polymerase chain reaction (RT-PCR). Second, we performed parthenogenetic activation (PA), in vitro fertilization (IVF), and somatic cell nuclear transfer (SCNT) to evaluate the embryonic developmental potential after hrG-CSF supplementation based on various concentrations (0 ng/mL, 10 ng/mL, 50 ng/mL, and 100 ng/mL) and durations (Un-treated, Days 0-3, Days 4-7, and Days 0-7) of IVC. Finally, we examined transcriptional levels of several marker genes in blastocysts. The results of our study showed that CSF3 transcript was present in all samples we assessed. CSF3-R was also detected, except in cumulus cells and blastocysts from PA. Furthermore, 10 ng/mL and Days 0-7 were the optimal concentration and duration for the viability of in vitro embryonic development, especially for SCNT-derived embryos. The rate of blastocyst formation and the total cell number of blastocysts were significantly enhanced, while the number and index of apoptotic nuclei were significantly decreased in optimal condition groups compared to others. Moreover, the transcriptional levels of anti-apoptotis- (BCL2), proliferation- (PCNA), and pluripotency- (POU5F1) related genes were dramatically upregulated. In conclusion, for the first time, we demonstrated that CSF3 and CSF3R were expressed in porcine reproductive organs, cells, and embryos. Additionally, we determined that hrG-CSF treatment improved porcine embryonic development capacity in vitro.
粒细胞集落刺激因子(G-CSF)是一种多功能细胞因子,属于造血生长因子家族。最近的研究表明,G-CSF 是人类卵母细胞和胚胎发育能力的预测生物标志物。我们的研究目的是确定 CSF3 及其受体(CSF3R)是否在猪母畜生殖组织(输卵管和子宫)、卵丘细胞和胚胎中表达,并研究人重组 G-CSF(hrG-CSF)在体外培养(IVC)中补充对植入前胚胎发育能力的影响。为此,我们首先进行了逆转录聚合酶链反应(RT-PCR)。其次,我们进行了孤雌激活(PA)、体外受精(IVF)和体细胞核移植(SCNT),以评估基于不同浓度(0ng/mL、10ng/mL、50ng/mL 和 100ng/mL)和持续时间(未处理、第 0-3 天、第 4-7 天和第 0-7 天)的 hrG-CSF 补充后的胚胎发育潜能。最后,我们检查了囊胚中几个标记基因的转录水平。我们的研究结果表明,CSF3 转录本存在于我们评估的所有样本中。除了卵丘细胞和 PA 产生的囊胚外,还检测到 CSF3-R。此外,10ng/mL 和第 0-7 天是体外胚胎发育存活的最佳浓度和持续时间,特别是对于 SCNT 衍生的胚胎。在最佳条件组中,囊胚形成率和囊胚总细胞数显著提高,而凋亡核的数量和指数则显著降低。此外,抗凋亡(BCL2)、增殖(PCNA)和多能性(POU5F1)相关基因的转录水平显著上调。总之,我们首次证明 CSF3 和 CSF3R 在猪生殖器官、细胞和胚胎中表达。此外,我们确定 hrG-CSF 处理可提高猪胚胎体外发育能力。