Conditional deletion of Wntless in granulosa cells causes impaired corpora lutea formation and subfertility.

ABSTRACT

WNT proteins are widely expressed in the murine ovaries. WNTLESS is a regulator essential for all WNTs secretion. However, the complexity and overlapping expression of WNT signaling cascades have prevented researchers from elucidating their function in the ovary. Therefore, to determine the overall effect of WNT on ovarian development, we depleted the Wntless gene in oocytes and granulosa cells. Our results indicated no apparent defect in fertility in oocyte-specific Wntless knockout mice. However, granulosa cell (GC) specific Wntless deletion mice were subfertile and recurred miscarriages. Further analysis found that GC-specific Wntless knockout mice had noticeably smaller corpus luteum (CL) in the ovaries than control mice, which is consistent with a significant reduction in luteal cell marker gene expression and a noticeable increase in apoptotic gene expression. Also, the deletion of Wntless in GCs led to a significant decrease in ovarian HCGR and ß-Catenin protein levels. In conclusion, Wntless deficient oocytes had no discernible impact on mouse fertility. In contrast, the loss of Wntless in GCs caused subfertility and impaired CL formation due to reduced LHCGR and ß-Catenin protein levels, triggering GC apoptosis.