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

Abstract

PurposeLH 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.MethodsThe 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.ResultsNTS 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.ConclusionsNTS 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.