Elucidation of the Mechanism of Meiotic Initiation by Retinoic Acid and Neuregulin

2013 Fiscal Year Final Research Report

• Project/Area Number: 22247008
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Morphology/Structure
• Research Institution: Kumamoto University
• Principal Investigator: ABE Shin-ichi 熊本大学, 事務局, 理事・副学長 (90109637)
• Co-Investigator(Kenkyū-buntansha): ETO Ko 熊本大学, 自然科学研究科, 准教授 (40359964) ; ARAKI Norie 熊本大学, 生命科学研究部(医), 准教授 (80253722)
• Project Period (FY): 2010-04-01 – 2014-03-31
• Keywords: 発生・分化 / 精巣 / 減数分裂開始 / neuregulin / ErbB

Research Abstract

We studied the role of neuregulin (NRG) in the initiation of meiosis, using mutant mice and in vitro cultures. Tamoxifen (TM) injection into Nrg1Ser–/– mutant mice, as well as dominant-negative ErbB4 transgenic mice, decreased proliferation of spermatogonia and meiotic initiation. In cultures of testicular fragments and purified spermatogonia, NRG1 and RA promoted spermatogonial proliferation and meiotic initiation. These results indicate that in juvenile testes RA induces meiosis indirectly through Sertoli cells when NRGs are upregulated and the NRGs directly induce meiosis in spermatogonia through ErbB4 receptor. Collectively, these results indicate that NRGs are essential for the proliferation of spermatogonia and meiotic initiation.
The studies in HeLa cells suggested that p80, which is generated from ErbB4 and translocates to the nuclei, interacts with a-enolase and inhibits NRG1-dependent cell proliferation by impairing the c-myc gene transcription.

Research Products

• [Journal Article] The interaction of the ErbB4 intracellular domain p80 with a-enolase in the nuclei is associated with the inhibition of neuregulin1-dependent cell proliferation (2014)
  • Author(s): Yamada, S., Marutsuka, M., Inoue, M., Zhang, J., Abe, S.-I., Ishibashi, K.Yamaguchi, N., Eto, K.
  • Journal Title: Int J Biochem Mol Biol Volume: (in press)
  • Peer Reviewed
• [Journal Article] Reconstruction of a seminiferous tubule-like structure in a 3 dimensional culture system of re-aggregated mouse neonatal testicular cells within a collagen matrix (2014)
  • Author(s): Zhang, J, Hatakeyama, J., Eto, K. and Abe, S.-I.
  • Journal Title: Gen Comp Endocrinol Volume: (in press)
  • DOI: 10.1016/j.ygcen.2014.03.030
  • Peer Reviewed
• [Journal Article] Nociceptin induces Rec8 phosphorylation and meiosis in postnatal murine testes (2013)
  • Author(s): Eto K, Shiotsuki M, Abe S-I
  • Journal Title: Endocrinology Volume: 154(8) Pages: 2891-2899
  • DOI: 10.1210/en.2012-1977
  • Peer Reviewed
• [Journal Article] Nociceptin is upregulated by FSH signaling in Sertoli cells in murine testes (2012)
  • Author(s): Eto K, Shiotsuki M, Sakai T, Abe S.
  • Journal Title: Biochem Biophys Res Commun Volume: 421(4) Pages: 678-683
  • DOI: 10.1016/j.bbrc.2012.04.061
  • Peer Reviewed
• [Journal Article] Loss of programmed cell death 4 induces apoptosis by promoting the translation of procaspase-3 mRNA (2012)
  • Author(s): Eto K, Goto S, Nakashima W, Ura Y, Abe SI.
  • Journal Title: Cell Death Differ Volume: 19(4) Pages: 573-581
  • DOI: 10.1038/cdd.2011.126
  • Peer Reviewed
• [Journal Article] Neuregulins are essential for spermatogonial proliferation and meiotic initiation in neonatal mouse testis (2011)
  • Author(s): Zhang J, Eto K, Honmyou A, Nakao K, Kiyonari H, Abe S.
  • Journal Title: Development Volume: 138(15) Pages: 3159-3168
  • DOI: 10.1242/dev.062380
  • Peer Reviewed
• [Journal Article] ErbB4 signals Neuregulin1-stimulated cell proliferation and c-fos gene expression through phosphorylation of serum response factor by mitogen-activated protein kinase cascade (2010)
  • Author(s): Eto K., Hommyo A., Yonemitsu R., and Abe S.-I.
  • Journal Title: Mol. Cell Biochem Volume: 339 Pages: 119-125
  • Peer Reviewed
• [Presentation] Reconstruction of seminiferous tubule-like structure in 3-D culture system of re-aggregated mouse testicular cells in vitro (2013)
  • Author(s): Abe, S.-I., et al
  • Organizer: the symposium "Molecular mechanisms of sex determination and differentiation", The 17th Int Cong Comp Endocrinol (ICCE)
  • Place of Presentation: Barcelona, Spain
  • Year and Date: 20130715-19
  • Invited
• [Presentation] Effect of NRG1 and ATRA on the proliferation and differentiation of undifferetitated spermatogonia in mouse (2012)
  • Author(s): Abe, S.-I., et al.
  • Organizer: 45th Annual Meeting of the Japanese Society of Developmental Biologists
  • Place of Presentation: Kobe
  • Year and Date: 20120528-31
• [Presentation] Neuregulins are essential in spermatogonial proliferation and meiosis initiation in neonatal mouse testis (2011)
  • Author(s): Abe, S.-I., et al.
  • Organizer: 44th Annual Meeting of the Japanese Society of Developmental Biologists
  • Place of Presentation: Ginowan, Okinawa
  • Year and Date: 20110518-21
• [Presentation] Neuregulins as downstream factors of retinoic acid induce meiosis in neonatal mouse testes in vitro (2010)
  • Author(s): Abe S.-I., et al.
  • Organizer: 11th International Symposium on Spermatology
  • Place of Presentation: OKINAWA
  • Year and Date: 20100624-29
• [Book] Roles of Neuregulins and Retinoic Acid in Spermatogonial Proliferation and Meiotic Initiation in Neonatal Mouse Testis. Sperm Cell Research in the 21st Century : Historical Discoveries to New Horizons (ed by Morisawa) (2012)
  • Author(s): Abe, S.-I., Zhang, J., Eto, K.
  • Total Pages: 256
  • Publisher: Adthree Publishing Co., Ltd., Tokyo, Japan