Relationship Between SnoN Expression And Mouse Follicular Development

Ski/SnoN belong to the ski family of proto-onceproteins. they can induce both oncogenic transformation and terminal muscle differentiation when expressed at high levels. Ski/SnoN are important regulators of signal transduction of transforming growth factor beta superfamily. Ski and SnoN are transcription factors that form both homodimers and heterodimers, and the latter is more active. Ski has been demonstrated to express in the granulosa cells of atretic follicles. Although SnoN promotes oncogenic transformation and cell proliferation, nothing is known about its role in ovarian function. So the purpose of the present study is to locate the SnoN protein in the ovaries and to further elucidate its biological role in the regulation of folliculogenesis and luteinigenesis. We assessed for the first time the expression and function of SnoN in mouse ovary, examined the cell-specific localization and regulation of SnoN protein levels during postnatal ovarian development, as well as gonadotropin-induced follicular development, ovulation, atresia and luteinization in immature mice. In addition, we examined the expression of Ski in the ovary.The results showed that: The data indicated that during the early stages of follicular development, such as follicle assembly, primary follicular development from primordial follicles, SnoN immunoreactivity was not detected in the whole ovary. positive staining for SnoN was detected for the first time in the interstitial compartment adjacent to the follicles at 7 days and the pattern of immunostaining remained constant. At 3 weeks of age follicles reach the small and medium antral stages. At these stages, theca cells differentiate into two layers, theca externa and theca interna. SnoN was detected in theca externa layer, but was not detected in theca interna. Besides, ovarian surface epithelial cells showed a clear immunoreactivity for SnoN.During gonadotropin-induced follicular growth, extensive immunoreactivity was apparent in theca and stromal compartments but not granulosa cells. In the interstitial compartment, the pattern of immunostaining for SnoN remained constant and was not affected by the stage of follicular development. Within the theca layers SnoN staining was heterogeneous. In the small follicles, SnoN was only detected in the theca externa layer, and was not detected in the theca interna. With the development of the follicles, the positive staining was detected in both theca externa and theca interna of the large antral follicles. During the follicular development, granulosa cells did not contain detectable levels of SnoN in the healthy follicles. During gonadotropin-induced ovulation and luteinization, a notable increase in staining intensity was observed in newly formed CL. Generally, 10 h after hCG injection, follicles begin ovulating, and subsequently CL formation starts. The data indicated that 12 h after hCG injection, SnoN was expressed in the luteinizing granulosa cells but at low levels, in contrast, 48 h after hCG, CL exhibited high levels of SnoN staining. SnoN was still not detected in granulosa cells of developing follicles at the same time points. SnoN immunoreactivity in atretic follicles: Atresia occurred in follicles during all stages of development up to the large antral stage. We then determined the relation between SnoN protein expression and follicle state in the immature mice. The presence of atretic follicles was assessed by TUNEL. The results showed when atresia was initiated in a follicle, a strong SnoN staining was detected in the granulosa layers.