Estrogen Receptor β2 Oversees Germ Cell Maintenance and Gonadal Sex Differentiation in Medaka, Oryzias latipes

T. Chakraborty, S. Mohapatra, Lin Yan Zhou, K. Ohta, Takahiro Matsubara, Taisen Iguchi, Yoshitaka Nagahama

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11 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)419-433
Number of pages15
JournalStem Cell Reports
Issue number2
Publication statusPublished - Aug 13 2019

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Genetics
  • Developmental Biology
  • Cell Biology


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