Treatment with the <scp>MAPK</scp> kinase inhibitor U0126 during the first two hours of in vitro maturation improves bovine oocyte developmental competence

Shinohara, Takashi; Ohta, Yuki; Kawate, Noritoshi; Takahashi, Masahiro; Sakagami, Nobutada; Inaba, Toshio; Tamada, Hiromichi

doi:10.1111/rda.13096

Cited by 4 publications

(6 citation statements)

References 9 publications

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“…At the last stage of folliculogenesis, MAPK is stimulated by LH through the ERK-MAPK signaling pathway and promotes GJA1 phosphorylation [33]. With GJA1 phosphorylation, the gap junction is lost, which decreases the concentration of cGMP (cyclic guanosine monophosphate) in oocytes and promotes the process of meiosis [34][35][36]. cAMP (cyclic adenosine monophosphate), a second messenger, has been known to induce oocyte meiotic processes.…”

Section: Discussionmentioning

confidence: 99%

Involvement of GJA1 and Gap Junctional Intercellular Communication between Cumulus Cells and Oocytes from Women with PCOS

Liu

Kong

Zhang

et al. 2020

BioMed Research International

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Polycystic ovary syndrome (PCOS) is a common female endocrine system disease that affects 17.8% of women of reproductive age and leads to infertility, obesity, glucose metabolic disorders, cardiovascular disease, and body-mind problems. However, the etiology of PCOS remains unclear. Follicular growth is disrupted as a result of ovarian hyperandrogenism and distorted intraovarian paracrine signaling in women with PCOS. Microcommunication between oocytes and cumulus cells plays a critical role in folliculogenesis. Gap junction alpha 1 (GJA1) plays a crucial role in the developing follicles by forming communication channels between cumulus cells and oocytes, but this has not yet been reported in women with PCOS. Therefore, we aimed to study the role of GJA1 in the microcommunication between oocytes and cumulus cells in women with PCOS. In our study, cumulus cell-oocyte complexes (COCs) from women were isolated via ultrasound-guided vaginal puncture, and oocytes were selected from COCs and categorized based on 3 oocyte maturation stages. Then, RT-qPCR and immunofluorescence analysis were performed to detect both the gene expression and protein of GJA1 in oocytes from women with and without PCOS. There was no statistically significant difference in age and BMI (body mass index), but patients with PCOS had a higher ratio of basic LH/FSH (luteinizing hormone/follicle-stimulating hormone), androstenedione, and total ovarian volume. The qRT-PCR results showed higher gene expression of GJA1 in oocytes without PCOS at the germinal vesicle (GV) stage compared with that of oocytes from women with PCOS. Immunofluorescence analysis showed that the expression level of GJA1 in oocytes from women with PCOS was very weak compared with that of oocytes from women without PCOS. In conclusion, GJA1 may play a critical role in the development of oogenesis arrest in women with PCOS throughout the oogenesis processes, including oogenesis and oocyte maturation.

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Section: Discussionmentioning

confidence: 99%

Involvement of GJA1 and Gap Junctional Intercellular Communication between Cumulus Cells and Oocytes from Women with PCOS

Liu

Kong

Zhang

et al. 2020

BioMed Research International

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“…In porcine oocytes, it was demonstrated that Cx43 is highly controlled by gonadotropins [ 59 , 60 ]. Thereby, the decrease in the concentration of cGMP in oocytes induces hydrolysis of cAMP, which promotes the meiotic process and maturation of oocytes [ 61 ].…”

Section: Pannexin and Connexin Involvement In Oocyte Maturationmentioning

confidence: 99%

Pannexins and Connexins: Their Relevance for Oocyte Developmental Competence

Kordowitzki

Sokołowska

Wasielak-Politowska³

et al. 2021

IJMS

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The oocyte is the major determinant of embryo developmental competence in all mammalian species. Although fundamental advances have been generated in the field of reproductive medicine and assisted reproductive technologies in the past three decades, researchers and clinicians are still trying to elucidate molecular factors and pathways, which could be pivotal for the oocyte’s developmental competence. The cell-to-cell and cell-to-matrix communications are crucial not only for oocytes but also for multicellular organisms in general. This latter mentioned communication is among others possibly due to the Connexin and Pannexin families of large-pore forming channels. Pannexins belong to a protein group of ATP-release channels, therefore of high importance for the oocyte due to its requirements of high energy supply. An increasing body of studies on Pannexins provided evidence that these channels not only play a role during physiological processes of an oocyte but also during pathological circumstances which could lead to the development of diseases or infertility. Connexins are proteins that form membrane channels and gap-junctions, and more precisely, these proteins enable the exchange of some ions and molecules, and therefore they do play a fundamental role in the communication between the oocyte and accompanying cells. Herein, the role of Pannexins and Connexins for the processes of oogenesis, folliculogenesis, oocyte maturation and fertilization will be discussed and, at the end of this review, Pannexin and Connexin related pathologies and their impact on the developmental competence of oocytes will be provided.

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“…Activation of the EGF/EGFR signaling cascade increases the expression of MAPK, which promotes the phosphorylation of connexin 43 (GJA1), causing the closure of gap junctions (11). On the other hand, activated EGFR also inhibits the production of cyclic guanosine monophosphate (cGMP) and suppresses meiosis (13). This is because cGMP triggers meiosis in oocytes by inhibiting the hydrolysis of cyclic adenosine monophosphate (cAMP).…”

Section: Introductionmentioning

confidence: 99%

Role of EGFR expressed on the granulosa cells in the pathogenesis of polycystic ovarian syndrome

et al. 2022

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Polycystic ovarian syndrome (PCOS) is one of the most common endocrinological disorders affecting between 6 to 20% of reproductive aged women. However, the etiology of PCOS is still unclear. Epidermal growth factor receptor (EGFR) plays a critical role in the growth and development of ovarian follicles. In our previous study, we showed that the expression level of EGFR was significantly higher in the cumulus granulosa cells from women with PCOS than that of normal women, suggesting that EGFR may play a potential role in the pathogenesis of PCOS. The present study further evaluated the association between EGFR and PCOS through both in clinical observation and animal experiments. We firstly validated the differential expression of EGFR in cumulus granulosa cells between PCOS patients and normal subjects by qRT-PCR and immunofluorescence staining. Then we generated a mouse model (n=20) of PCOS by injecting dehydroepiandrosterone (DHEA). The PCOS mice were then injected with an E corpus GFR inhibitor (AG1478) (n=10), which significantly improved the sex hormone levels in the estrous cycle stage, and the serum levels of LH, FSH and testosterone were compared with the PCOS mice without EGFR inhibitor treatment (n=10). Decreasing the expression level of EGFR in the PCOS mice also improved the ovulatory function of their ovaries which was indicated by the multifarious follicle stage in these mice as compared with the PCOS mice without EGFR inhibitor treatment. Also, the number of corpopa lutea were higher in the control group and the EGFR inhibitor treated group than in the PCOS group. The sex hormone levels and reproductive function were not significantly different between the control mice and the PCOS mice treated with the EGFR inhibitor. Our results demonstrated that EGF/EGFR signaling affected the proliferation of cumulus granulosa cells, oocyte maturation and meiosis, and played a potential role in the pathogenesis of PCOS. Therefore, the selective inhibition of EGFR may serve as a novel strategy for the clinical management of PCOS.

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Treatment with the MAPK kinase inhibitor U0126 during the first two hours of in vitro maturation improves bovine oocyte developmental competence

Cited by 4 publications

References 9 publications

Involvement of GJA1 and Gap Junctional Intercellular Communication between Cumulus Cells and Oocytes from Women with PCOS

Involvement of GJA1 and Gap Junctional Intercellular Communication between Cumulus Cells and Oocytes from Women with PCOS

Pannexins and Connexins: Their Relevance for Oocyte Developmental Competence

Role of EGFR expressed on the granulosa cells in the pathogenesis of polycystic ovarian syndrome

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