TY - JOUR
T1 - Estrogen Receptor β2 Oversees Germ Cell Maintenance and Gonadal Sex Differentiation in Medaka, Oryzias latipes
AU - Chakraborty, T.
AU - Mohapatra, S.
AU - Zhou, Lin Yan
AU - Ohta, K.
AU - Matsubara, Takahiro
AU - Iguchi, Taisen
AU - Nagahama, Yoshitaka
N1 - Funding Information:
The authors are thankful to Shinichi Miyagawa (Associate Professor, Tokyo University of Science, Japan) and Yukiko Ogino (Associate Professor, Kyushu University, Japan) for their help with the research. The authors extend their sincere gratitude to National Bio Resource Project Medaka of Ministry of Education, Culture, Sports, Science and Technology, Japan for their help with various transgenic and inbred medaka. This work was in part supported by grants from Science and Technology Agency (SORST Program) and the Ministry of Education, Culture, Sports, Science and Technology , Japanese Society for the Promotion of Science Kakenhi, grant nos. 23688022 , 16H04981 , 23380110 , 18K14520 , and 19H03049 ; Sumitomo grant no. 180959 ; and Ehime University post-doctoral research grant, Japan.
PY - 2019/8/13
Y1 - 2019/8/13
N2 - In vertebrates, estrogen receptors are essential for estrogen-associated early gonadal sex development. Our previous studies revealed sexual dimorphic expression of estrogen receptor β2 (ERβ2) during embryogenesis of medaka, and here we investigated the functional importance of ERβ2 in female gonad development and maintenance using a transgenerational ERβ2-knockdown (ERβ2-KD) line and ERβ2-null mutants. We found that ERβ2 reduction favored male-biased gene transcription, suppressed female-responsive gene expression, and affected SDF1a and CXCR4b co-assisted chemotactic primordial germ cell (PGC) migration. Co-overexpression of SDF1a and CXXR4b restored the ERβ2-KD/KO associated PGC mismigration. Further analysis confirmed that curtailment of ERβ2 increased intracellular Ca2+ concentration, disrupted intra- and extracellular calcium homeostasis, and instigated autophagic germ cell degradation and germ cell loss, which in some cases ultimately affected the XX female sexual development. This study is expected improve our understanding of germ cell maintenance and sex spectrum, and hence open new avenues for reproductive disorder management. In this article, Chakraborty et al. find that estrogen receptor β2 (ERβ2) plays multifaceted crucial roles in medaka gonadal development and sexuality. ERβ2 predominantly expresses in germ cells, influences the SDF1/CXCR4 chemotaxis, PGC migration, and death, and regulates germ cell proliferation and various sex-biased gene transcriptions that are essential for gonadal sex assignment and maintenance.
AB - In vertebrates, estrogen receptors are essential for estrogen-associated early gonadal sex development. Our previous studies revealed sexual dimorphic expression of estrogen receptor β2 (ERβ2) during embryogenesis of medaka, and here we investigated the functional importance of ERβ2 in female gonad development and maintenance using a transgenerational ERβ2-knockdown (ERβ2-KD) line and ERβ2-null mutants. We found that ERβ2 reduction favored male-biased gene transcription, suppressed female-responsive gene expression, and affected SDF1a and CXCR4b co-assisted chemotactic primordial germ cell (PGC) migration. Co-overexpression of SDF1a and CXXR4b restored the ERβ2-KD/KO associated PGC mismigration. Further analysis confirmed that curtailment of ERβ2 increased intracellular Ca2+ concentration, disrupted intra- and extracellular calcium homeostasis, and instigated autophagic germ cell degradation and germ cell loss, which in some cases ultimately affected the XX female sexual development. This study is expected improve our understanding of germ cell maintenance and sex spectrum, and hence open new avenues for reproductive disorder management. In this article, Chakraborty et al. find that estrogen receptor β2 (ERβ2) plays multifaceted crucial roles in medaka gonadal development and sexuality. ERβ2 predominantly expresses in germ cells, influences the SDF1/CXCR4 chemotaxis, PGC migration, and death, and regulates germ cell proliferation and various sex-biased gene transcriptions that are essential for gonadal sex assignment and maintenance.
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U2 - 10.1016/j.stemcr.2019.07.013
DO - 10.1016/j.stemcr.2019.07.013
M3 - Article
C2 - 31412286
AN - SCOPUS:85070343153
VL - 13
SP - 419
EP - 433
JO - Stem Cell Reports
JF - Stem Cell Reports
SN - 2213-6711
IS - 2
ER -