論文 - 詳細
| RRC ID | 87710 |
|---|---|
| 著者 | Sakai-Yamada Y, Myosho T, Kayo D, Kanda S, Kobayashi T. |
| タイトル | Estrogenic control of germ cell differentiation in medaka: independence of early sex dimorphism from zygotic estrogen and receptor signaling. |
| ジャーナル | Front Endocrinol (Lausanne) |
| Abstract |
BACKGROUND:Estrogen signaling is essential for ovarian differentiation in vertebrates, but its developmental onset and specific roles during early gonadogenesis remain unclear. In medaka (Oryzias latipes), the first morphological sex difference appears as a higher germ cell number in XX compared with XY embryos before hatching. Recently, we demonstrated that zygotically synthesized estrogen was dispensable for early germ cell sex difference but essential for subsequent oocyte meiotic progression and ovarian fate maintenance. Nevertheless, whether these phenomena depend on maternal estrogen or zygotic estrogen signaling mediated by nuclear estrogen receptors (nEsrs) is unknown. OBJECTIVE:To clarify the receptor-level requirement of estrogen signaling, we generated esr1/2a/2b triple knockout (ΔnEsrs) medaka using CRISPR/Cas9 genome editing. By comparing these receptor-deficient mutants with our previous ligand-deficient (Δcyp19a1a/1b double knockout) model, we aimed to determine whether estrogen signaling is involved in the establishment of the early germ cell number difference or acts later to control meiotic progression and ovarian maintenance. METHODS:We established ΔnEsrs medaka using CRISPR/Cas9 and analyzed gonadal histology, germ cell kinetics, and expression of steroidogenic enzyme genes, sex differentiation-related genes, and oocyte-specific expressed genes during early development. RESULTS:ΔnEsrs mutants displayed normal early germ cell number and sex-specific differences at hatching (0 dph). At 10 dph, diplotene oocytes were markedly reduced, accompanied by significant downregulation of oocyte-specific genes, figa, 42sp50, as well as cyp19a1a and foxl2 mRNA. However, ΔnEsrs did not cause feedback regulation on other hypothalamus-pituitary-gonad (HPG) axis gene expression. CONCLUSION:Our results demonstrate that estrogen signaling, both at the ligand and receptor levels, is dispensable for establishing the early germ cell sex difference but essential for subsequent oocyte meiotic progression and ovarian fate maintenance. This establishes a two-step estrogenic control model, redefining the developmental timing of estrogen action during the early phase of gonadal differentiation in vertebrate reproduction. |
| 巻・号 | 16 |
| ページ | 1769798 |
| 公開日 | 2025-1-1 |
| DOI | 10.3389/fendo.2025.1769798 |
| PMID | 41635537 |
| PMC | PMC12862824 |
| MeSH | Animals Cell Differentiation* / drug effects Estrogens* / metabolism Estrogens* / pharmacology Female Gene Expression Regulation, Developmental Germ Cells* / cytology Germ Cells* / drug effects Germ Cells* / metabolism Male Oryzias* / metabolism Ovary / metabolism Receptors, Estrogen* / genetics Receptors, Estrogen* / metabolism Sex Characteristics Signal Transduction Zygote* / metabolism |
| IF | 3.644 |
| リソース情報 | |
| メダカ | MT1198 MT1850 MT1851 |