Neurotensin induces sustainable activation of the ErbB-ERK1/2 pathway, which is required for developmental competence of oocytes in mice.

IF 2.7 3区医学 Q2 OBSTETRICS & GYNECOLOGY

Reproductive Medicine and Biology Pub Date : 2024-03-20 eCollection Date: 2024-01-01 DOI:10.1002/rmb2.12571

Asako Okamoto, Tomoya Nakanishi, Shingo Tonai, Masayuki Shimada, Yasuhisa Yamashita

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引用次数: 0

Abstract

Purpose: LH induces the expression of EGF-like factors and their shedding enzyme (ADAM17) in granulosa cells (GCs), which is essential for ovulation via activation of the ErbB-ERK1/2 pathway in cumulus cells (CCs). Neurotensin (NTS) is reported as a novel regulator of ovulation, whereas the NTS-induced maturation mechanism in oocytes remains unclear. In this study, we focused on the role of NTS in the expression of EGF-like factors and ErbBs, and ADAM17 activity, during oocyte maturation and ovulation in mice.

Methods: The expression and localization in GC and CC were examined. Next, hCG and NTS receptor 1 antagonist (SR) were injected into eCG-primed mice, and the effects of SR on ERK1/2 phosphorylation were investigated. Finally, we explored the effects of SR on the expression of EGF-like factors and ErbBs, and ADAM17 activity in GC and CC.

Results: NTS was significantly upregulated in GC and CC following hCG injection. SR injection suppressed oocyte maturation and ERK1/2 phosphorylation. SR also downregulated part of the expression of EGF-like factors and their receptors, and ADAM17 activity.

Conclusions: NTS induces oocyte maturation through the sustainable activation of the ERK1/2 signaling pathway by upregulating part of the EGF-like factor-induced pathway during oocyte maturation in mice.

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神经营养素诱导 ErbB-ERK1/2 通路的持续激活，这是小鼠卵母细胞发育能力所必需的。

目的：LH可诱导颗粒细胞（GCs）中EGF样因子及其脱落酶（ADAM17）的表达，通过激活积层细胞（CCs）中的ErbB-ERK1/2途径，EGF样因子及其脱落酶对排卵至关重要。据报道，神经营养素（NTS）是一种新型的排卵调节因子，但NTS诱导卵母细胞成熟的机制仍不清楚。在本研究中，我们重点研究了NTS在小鼠卵母细胞成熟和排卵过程中对EGF样因子和ErbBs的表达以及ADAM17活性的作用：方法：研究了GC和CC中NTS的表达和定位。接下来，向eCG刺激的小鼠注射hCG和NTS受体1拮抗剂（SR），并研究SR对ERK1/2磷酸化的影响。最后，我们探讨了SR对GC和CC中EGF样因子和ErbBs的表达以及ADAM17活性的影响：结果：注射hCG后，NTS在GC和CC中明显上调。结果：注射 hCG 后，NTS 在 GC 和 CC 中明显上调，注射 SR 可抑制卵母细胞成熟和 ERK1/2 磷酸化。结果：注射 hCG 后，NTS 在 GC 和 CC 中明显上调：结论：在小鼠卵母细胞成熟过程中，NTS通过上调部分EGF样因子诱导的途径，持续激活ERK1/2信号通路，从而诱导卵母细胞成熟。

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

Reproductive Medicine and Biology Multiple-

CiteScore

5.70

自引率

5.90%

发文量

审稿时长

20 weeks

期刊介绍： Reproductive Medicine and Biology (RMB) is the official English journal of the Japan Society for Reproductive Medicine, the Japan Society of Fertilization and Implantation, the Japan Society of Andrology, and publishes original research articles that report new findings or concepts in all aspects of reproductive phenomena in all kinds of mammals. Papers in any of the following fields will be considered: andrology, endocrinology, oncology, immunology, genetics, function of gonads and genital tracts, erectile dysfunction, gametogenesis, function of accessory sex organs, fertilization, embryogenesis, embryo manipulation, pregnancy, implantation, ontogenesis, infectious disease, contraception, etc.