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

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...

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Main Authors: Asako Okamoto, Tomoya Nakanishi, Shingo Tonai, Masayuki Shimada, Yasuhisa Yamashita
Format: Article
Language:English
Published: Wiley 2024-01-01
Series:Reproductive Medicine and Biology
Subjects:
Online Access:https://doi.org/10.1002/rmb2.12571
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author Asako Okamoto
Tomoya Nakanishi
Shingo Tonai
Masayuki Shimada
Yasuhisa Yamashita
author_facet Asako Okamoto
Tomoya Nakanishi
Shingo Tonai
Masayuki Shimada
Yasuhisa Yamashita
author_sort Asako Okamoto
collection DOAJ
description 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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spelling doaj-art-cbe6793a33dd47acae0f41abbb43c0e22025-08-20T02:52:37ZengWileyReproductive Medicine and Biology1445-57811447-05782024-01-01231n/an/a10.1002/rmb2.12571Neurotensin induces sustainable activation of the ErbB–ERK1/2 pathway, which is required for developmental competence of oocytes in miceAsako Okamoto0Tomoya Nakanishi1Shingo Tonai2Masayuki Shimada3Yasuhisa Yamashita4Graduate School of Comprehensive Scientific Research Prefectural University of Hiroshima Shobara JapanGraduate School of Comprehensive Scientific Research Prefectural University of Hiroshima Shobara JapanGraduate School of Comprehensive Scientific Research Prefectural University of Hiroshima Shobara JapanGraduate School of Integrated Sciences for Life Hiroshima University Higashi‐Hiroshima JapanGraduate School of Comprehensive Scientific Research Prefectural University of Hiroshima Shobara JapanAbstract 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.https://doi.org/10.1002/rmb2.12571neurotensinERK1/2cumulus cellsgranulosa cellsoocyte maturation
spellingShingle Asako Okamoto
Tomoya Nakanishi
Shingo Tonai
Masayuki Shimada
Yasuhisa Yamashita
Neurotensin induces sustainable activation of the ErbB–ERK1/2 pathway, which is required for developmental competence of oocytes in mice
Reproductive Medicine and Biology
neurotensin
ERK1/2
cumulus cells
granulosa cells
oocyte maturation
title Neurotensin induces sustainable activation of the ErbB–ERK1/2 pathway, which is required for developmental competence of oocytes in mice
title_full Neurotensin induces sustainable activation of the ErbB–ERK1/2 pathway, which is required for developmental competence of oocytes in mice
title_fullStr Neurotensin induces sustainable activation of the ErbB–ERK1/2 pathway, which is required for developmental competence of oocytes in mice
title_full_unstemmed Neurotensin induces sustainable activation of the ErbB–ERK1/2 pathway, which is required for developmental competence of oocytes in mice
title_short Neurotensin induces sustainable activation of the ErbB–ERK1/2 pathway, which is required for developmental competence of oocytes in mice
title_sort neurotensin induces sustainable activation of the erbb erk1 2 pathway which is required for developmental competence of oocytes in mice
topic neurotensin
ERK1/2
cumulus cells
granulosa cells
oocyte maturation
url https://doi.org/10.1002/rmb2.12571
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