Zhejiang Key Laboratory of Organ Development and Regeneration, Institute of Developmental and Regenerative Biology, College of Life and Environmental Sciences, Hangzhou Normal University, Hangzhou, 310036, People's Republic of China.
Plant Genomics & Molecular Improvement of Colored Fiber Lab, College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou, 310018, People's Republic of China.
Mol Cell Endocrinol. 2021 Feb 15;522:111142. doi: 10.1016/j.mce.2020.111142. Epub 2021 Jan 7.
WNT ligand transporter Wls is essential for the WNT dependent developmental and pathogenic processes. The spatiotemporal expression pattern of Wls was investigated in this study. Immature female mice (21-22 days old) were treated with 5 IU, pregnant mare's serum gonadotrophin (PMSG) to stimulate follicular development, followed 48 h later by injection with 5 IU, human chorionic gonadotrophin (hCG) to induce ovulation. The expression of Wls was stimulated in granulosa cells and the forming corpus luteum after hCG administration. To study the function of Wls, the Amhr2 strain was used to target deletion of Wls in granulosa cells. The deletion of Wls caused a significant decrease in the fertility of Wls female mice. In female Wls mice, decreased ovarian size and number of antral follicles were found. The number of corpus luteum in immature PMSG/hCG primed Wls mice was much less than that in the control group. Compared with control animals, Wls mice have lower serum progesterone levels. RNA sequencing was used to identify genes regulated by Wls after hCG treatment. Several genes known to be critical for follicle development and steroidogenesis were significantly down-regulated, such as Fshr, Lhcgr, Sfrp4, Inhba, Cyp17a1, Hsd3b1, and Hsd17b7. The expression of WNT signaling downstream target genes, Bmp2 and Cyp19a1, also decreased significantly in Wls ovary. In summary, the findings of this study suggest that Wls is critical for female fertility and luteinization.
WNT 配体转运蛋白 Wls 对于 WNT 依赖的发育和致病过程至关重要。本研究调查了 Wls 的时空表达模式。用 5 IU 孕马血清促性腺激素（PMSG）处理 21-22 天大的雌性未成年小鼠以刺激卵泡发育，48 小时后用 5 IU 人绒毛膜促性腺激素（hCG）诱导排卵。hCG 给药后，Wls 在颗粒细胞和正在形成的黄体中表达受到刺激。为了研究 Wls 的功能，使用 Amhr2 株在颗粒细胞中靶向缺失 Wls。Wls 缺失导致 Wls 雌性小鼠的生育能力显著下降。在雌性 Wls 小鼠中，发现卵巢体积和窦前卵泡数量减少。在不成熟的 PMSG/hCG 启动的 Wls 小鼠中，黄体数量明显少于对照组。与对照动物相比，Wls 小鼠的血清孕激素水平较低。用 RNA 测序鉴定 hCG 处理后受 Wls 调节的基因。一些已知对卵泡发育和类固醇生成至关重要的基因，如 Fshr、Lhcgr、Sfrp4、Inhba、Cyp17a1、Hsd3b1 和 Hsd17b7，表达显著下调。WNT 信号下游靶基因 Bmp2 和 Cyp19a1 的表达在 Wls 卵巢中也显著降低。总之，这项研究的结果表明，Wls 对雌性生育力和黄体化至关重要。
