Spermatogonial stem cells (SSCs; also known as Asingle [As] spermatogonia in mice) divide to self-renew or to produce progenitor cells known as Apaired(Apr) spermatogonia in basal compartment of seminiferous tubules of mammalian testis. These characterized cells are the finally differentiated product of a developmental process referred to as “spermatogenesis.” In the development of SSCs it is critical to maintain a balance between self-renewal and differentiation. because an excess of either process will lead to infertility. these two processes are tightly controlled by intrinsic signals of SSCs and extrinsic signals from the microenvironment, known as the SSC niche. The SSC niche is formed by Sertoli cells, the only somatic cells found inside the seminiferous tubules. The WNT/β-catenin pathway is known to regulate Sertoli cell functions critical to their capacity to support spermatogenesis in the postnatal testis, but The mechanisms and factors of the pathway are not well known. We found a factor TLE3 (Transducin Like Enhancer Of Split 3). The transcriptional co-repressor TLE family is known to function as transcription co-repressors within the context of Wnt signaling by interacting with histone deacetylase HDAC2. We examined the expression level of TLE3 in various mouse tissues. As a result of RT-PCR, TLE3 showed significantly higher expression in testis than that in other tissues. Immunofluorescent analysis revealed that TLE3 and HDAC2 expression are differentially regulated in the mouse testis during postnatal development. In adult testis, TLE3 and HDAC2 were co-expressed in Sertoli cells. TLE3 and HDAC2 protein are also located in nucleus in mouse TM4 Sertoli cells. Taken together, TLE3 may play a role in regulating WNT/β-catenin pathway via interaction with HDAC2 in Sertoli cell. Futher studies are needed to look into factors that regulated by siTLE3 in Sertoli cell and interated with TLE3 in WNT/β-catenin pathway.

The Hippo signaling pathway is essential for regulating proliferation, differentiation, and apoptosis in mammalian cells. Hippo signaling pathway exists in most body tissues and organs, where it controls the size of organs and tissues by keeping cell growth in check and promoting cell death as needed. It has been reported that the members of Hippo signaling pathway are highly expressed in mammalian ovaries and uteri. However, the regulatory mechanism of this pathway in the uterus during estrous cycle regulation remains unclear. Serine/Threonine Protein Kinase 4 (STK4, also known as MST1, a homolog of Hippo in Drosophila) is a major factor of Hippo signaling pathway. However STK4 in the mouse uterus has not yet been examined. The purpose of our study was to determine the expression of STK4 during the estrous cycle and regulation by estrogen in the mouse uterus. We found that STK4 was dynamically expressed in uterine endometrium during the estrous cycle. STK4 highly expressed at the estrus, diestrus, and were found to dramatically decrease as it progressed to the proestrus, metestrus stage of uterus during the estrous cycle. Expression of STK4 was dominant in glandular epithelial and luminal epithelial of proestrus, estrus, and diestrus stage, whereas in metestrus stage, expression of gene intensity was faint. Estrogen or estrogen receptor antagonist ICI 182,780 treatment, in ovariectomized mouse uterus, Expression of STK4 and its downstream genes were increased by estrogen. Our results show that the Hippo signaling pathway is estrogen-dependent in the mouse uterus. These informations will give us on sights to understand uterine dynamics during the estrous cycle.