The function of Wls in ovarian development.

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.