Park Chan Jin, Oh Ji-Eun, Lin PoChing, Zhou Sherry, Bunnell Mary, Bikorimana Emmanuel, Spinella Michael J, Lim Hyunjung Jade, Ko CheMyong J
Department of Comparative Biosciences, College of Veterinary Medicine, University of Illinois at Urbana-Champaign, Urbana, IL 61802, USA.
Epivara, Inc., Research Park, Champaign, IL 61820, USA.
Endocrinology. 2025 Jan 6;166(2). doi: 10.1210/endocr/bqaf006.
This study uncovers a dynamic shift in estrogen receptor expression during granulosa cell (GC) differentiation in the ovary, highlighting a transition from estrogen receptor alpha (ESR1) to estrogen receptor beta (ESR2). Using a transgenic mouse model with Esr1-iCre-mediated Esr2 deletion, we demonstrate that ESR2 expression is absent in GCs derived from ESR1-expressing ovarian surface epithelium (OSE) cells. Single-cell analysis of the OSE-GC lineage reveals a developmental trajectory from Esr1-expressing OSE cells to Foxl2-expressing pre-GCs, culminating in GCs exclusively expressing Esr2. Transcriptome analyses identified vasculature-derived TGFβ1 ligands as key regulators of this transition. Supporting this, TGFβ1 treatment of cultured embryonic ovaries reduced Esr1 expression while promoting Esr2 expression. This study underscores the capability of GCs to switch from ESR1 to ESR2 expression as a fundamental aspect of normal differentiation.
本研究揭示了卵巢颗粒细胞（GC）分化过程中雌激素受体表达的动态变化，突出了从雌激素受体α（ESR1）到雌激素受体β（ESR2）的转变。利用Esr1-iCre介导的Esr2缺失的转基因小鼠模型，我们证明在源自表达ESR1的卵巢表面上皮（OSE）细胞的GC中不存在ESR2表达。对OSE-GC谱系的单细胞分析揭示了从表达Esr1的OSE细胞到表达Foxl2的前颗粒细胞的发育轨迹，最终形成仅表达Esr2的GC。转录组分析确定血管衍生的TGFβ1配体是这种转变的关键调节因子。支持这一点的是，用TGFβ1处理培养的胚胎卵巢可降低Esr1表达，同时促进Esr2表达。本研究强调了颗粒细胞从ESR1表达转换为ESR2表达的能力是正常分化的一个基本方面。
