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

Tapas Chakraborty,Yoshitaka Nagahama,Sipra Mohapatra,Takahiro Matsubara,Taisen Iguchi,Lin Yan Zhou,Kohei Ohta

doi:10.1016/j.stemcr.2019.07.013

Abstract

SummaryIn 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.

Highlights

Sex steroids and their receptors harmoniously maintain the reproductive physiology, and any disruption in sexual development leads to a huge impact on individual or species physiology (Windsor et al, 2018)
Based on E2-dependent ERb1 and estrogen receptor b2 (ERb2) expression profiles in medaka embryos, we hypothesized that both these ERb subtypes work, respectively, on ‘‘cessation of male germ cell proliferation’’ and ‘‘mitotic burst in female.’’ the present agonist and antagonist treatments further corroborate that ERb1 and ERb2 has an antagonistic role in medaka (Chakraborty et al, 2011)
ERb2 Is Critical for Early Gonadal Development Earlier, we reported that ERb2 expression peaks at 7 days after fertilization in the germ cells of XX medaka (Chakraborty et al, 2011)

Summary

Introduction

Sex steroids and their receptors harmoniously maintain the reproductive physiology, and any disruption in sexual development leads to a huge impact on individual or species physiology (Windsor et al, 2018). Germ and somatic cells are two essential variables in gonadal differentiation and sexual identity in mouse, chicken, and fish (DeFalco and Capel, 2009). An important model species for gonadal sex determination and differentiation studies (Matsuda et al, 2002), the early gonadal settlement of PGCs is regulated by SDF1/CXCR4-mediated chemotactic migration (Herpin et al, 2008; Kurokawa et al, 2007). Later, during medaka sex differentiation, both germ and somatic cells co-operatively regulate the gonadal development in an estrogen-dependent manner (Kurokawa et al, 2007) and help the PGCs to undergo a proliferative mitosis and meiosis in females, while restricting proliferation in males

Methods

Results

Discussion

Conclusion