NEK2 supports porcine embryonic development by modulating the AKT signaling pathway

IF 5.2 2区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Life sciences Pub Date : 2025-04-14 DOI:10.1016/j.lfs.2025.123640

Se-Been Jeon , Hyo-Gu Kang , Min Ju Kim , Ji Hyeon Yun , Eun Young Choi , Bong-Seok Song , Sun-Uk Kim , Seong-Keun Cho , Pil-Soo Jeong , Bo-Woong Sim

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引用次数: 0

Abstract

Aims

Serine/threonine kinase NIMA-related kinase 2 (NEK2) plays a crucial role in regulating the cell cycle and DNA damage response. This study explored the mechanisms by which NEK2 inhibition affects porcine embryonic development.

Materials and methods

To explore the role of NEK2 in porcine embryonic development, we used the NEK2 inhibitor JH295 and the AKT activator SC79. Various staining methods, including EdU, EU, OPP, TUNEL assay, real-time PCR, immunocytochemistry, and Western blotting, were used to identify the effects of NEK2 inhibition on developmental competence, DNA damage, and the related mechanisms in porcine embryos.

Key findings

NEK2 inhibition significantly reduced the cleavage rate and blastocyst formation rate. Abnormal development was associated with decreased expression of genes related to zygotic genome activation and significantly reduced the levels of EdU, EU, and OPP. Notably, NEK2 inhibition decreased the levels of p-AKT and AKT, as well as their transcript levels. While NEK2 inhibition reduced the rates of cleavage and blastocyst formation as well as total cell number, all of these effects were reversed by SC79 co-treatment. The proportions of expanded blastocyst and cell survival and the trophectoderm cell numbers were similarly restored to control levels following combined treatment with SC79. Furthermore, the reduced levels of EdU, EU, and OPP by NEK2 inhibition were completely restored by SC79 co-treatment. NEK2 inhibition had a negative impact on DNA integrity, and this effect was inhibited by SC79 co-treatment.

Significance

Together, these results suggest that NEK2 plays a crucial role in porcine embryonic development by regulating the AKT signaling pathway.

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NEK2通过调节AKT信号通路支持猪胚胎发育

丝氨酸/苏氨酸激酶尼玛相关激酶2 （NEK2）在调节细胞周期和DNA损伤反应中起重要作用。本研究探讨了NEK2抑制影响猪胚胎发育的机制。为了研究NEK2在猪胚胎发育中的作用，我们使用了NEK2抑制剂JH295和AKT激活剂SC79。采用EdU、EU、OPP、TUNEL、real-time PCR、免疫细胞化学、Western blotting等多种染色方法鉴定NEK2抑制对猪胚胎发育能力、DNA损伤的影响及其相关机制。关键发现snek2抑制显著降低了卵裂率和囊胚形成率。发育异常与合子基因组激活相关基因的表达减少有关，EdU、EU和OPP水平显著降低，值得注意的是，NEK2抑制降低了p-AKT和AKT的水平及其转录物水平。虽然NEK2抑制降低了卵裂率和囊胚形成率以及总细胞数，但所有这些作用都被SC79共处理逆转。在与SC79联合治疗后，囊胚扩张比例和细胞存活率以及滋养外胚层细胞数量同样恢复到对照水平。此外，通过SC79共处理，NEK2抑制导致的EdU、EU和OPP水平完全恢复。NEK2抑制对DNA完整性有负面影响，SC79共处理可抑制这种影响。综上所述，这些结果表明NEK2通过调节AKT信号通路在猪胚胎发育中起着至关重要的作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Life sciences 医学-药学

CiteScore

12.20

自引率

1.60%

发文量

841

审稿时长

6 months

期刊介绍： Life Sciences is an international journal publishing articles that emphasize the molecular, cellular, and functional basis of therapy. The journal emphasizes the understanding of mechanism that is relevant to all aspects of human disease and translation to patients. All articles are rigorously reviewed. The Journal favors publication of full-length papers where modern scientific technologies are used to explain molecular, cellular and physiological mechanisms. Articles that merely report observations are rarely accepted. Recommendations from the Declaration of Helsinki or NIH guidelines for care and use of laboratory animals must be adhered to. Articles should be written at a level accessible to readers who are non-specialists in the topic of the article themselves, but who are interested in the research. The Journal welcomes reviews on topics of wide interest to investigators in the life sciences. We particularly encourage submission of brief, focused reviews containing high-quality artwork and require the use of mechanistic summary diagrams.