Estrogen-Mediated Regulation of Fam3d in Mouse Uterus During the Estrous Cycle

作者：Hyukjung Kim, Byeongseok Kim, Joohee Kim, Yeonju Suh, Jimin Lee, Sangok Park, Man Ryul Lee, Hoi Chang Lee, Youngsok Choi · 发表于：International Journal of Molecular Sciences · 年份：2025 · DOI：10.3390/ijms262411840 · 被引用次数：3 · 研究领域：Reproductive System and Pregnancy、Pregnancy and preeclampsia studies、Hypothalamic control of reproductive hormones

In mice, the uterus undergoes dynamic changes regulated by estrogen and progesterone during the estrous cycle. Proper regulation of these changes is critical for successful pregnancy. The Family with sequence similarity 3 (Fam3) gene family, comprising Fam3a, Fam3b, Fam3c, and Fam3d, encodes cytokine-like proteins, but their uterine roles remain unclear. This study examined Fam3 expression in the mouse uterus across the estrous cycle and assessed estrogen-dependent regulation. RNA-seq analysis revealed increased Fam3b, Fam3c, and Fam3d expression during proestrus and estrus. Notably, Fam3d showed dynamic regulation, peaking in these stages. To test estrogen regulation, estradiol was administered to ovariectomized mice, showing maximal Fam3d expression at 24 h post-injection. ERα antagonist treatment blocked this induction, indicating ERα-mediated regulation. Immunofluorescence localized FAM3D to the cytoplasm of luminal and glandular epithelia, especially in the apical region, with no stromal or nuclear expression. These findings suggest that estrogen and Erα (Estrogen receptor alpha) signaling control Fam3d expression, implicating FAM3D in uterine epithelial function. This study provides novel insights into Fam3d’s role in uterine physiology and a foundation for exploring its function in reproduction.