Potential Role of WNT4 in the Avian Oviduct Development and Ovarian Carcinogenesis

Abstract

The chicken oviduct is well known as a model for research on hormone action, including effects of estrogen and progesterone. Indeed, development of the chicken oviduct is mainly induced by sex steroid hormone, estrogen. The yolk and white of eggs from chickens contain proteins and other molecules either secreted or transported by cells of the reproductive tract or secreted by the liver and transported to the ovarian follicles of laying hens. The wingless-type MMTV integration site family of proteins (WNTs) are highly conserved secreted lipid-modified signaling molecules that play a variety of pivotal roles in developmental events. Of these, the WNT4 is well known to be involved in genital development in fetuses of mammalian species. However, in chickens, there are a few studies on the expression of WNT4 gene in the oviduct of hens. Therefore we investigated expression profiles, as well as hormonal and post-transcriptional regulation of WNT4 gene expression in the reproductive tract of female chickens. In this study, WNT4 mRNA had a differential expression pattern, concerned with cell- and tissue specific expression, in chicken oviduct. In addition, treatment of young chicks with DES (Diethylstilbestrol) stimulated WNT4 only in the glandular epithelial cells of the isthmus and shell gland of the oviduct. Furthermore, miR-302b which is one of microRNAs may influence expression and regulation of WNT4-FZD2 signaling pathway-related genes in laying hens. Moreover, the WNT4 is expressed predominantly in the glandular epithelium of cancerous ovaries, but not in normal ovaries of hens. We also researched temporal and cell specific expression of selected solute carriers (SLCs) genes at 3 h and 20 h post-ovulation and regulation of their expression by miRNAs. The SLCs are membrane proteins which transport various types of molecules across the cell membrane. Although SLC genes have been investigated in mammals including humans and mice, there are a few studies on the expression of SLC genes in the oviduct of hens. In this study, the expression patterns of selected SLC genes (SLC1A4, SLC4A5, SLC7A3, SLC13A2, SLC35B4) also showed that the pattern was cell and tissue specific in the chicken oviduct at 3h and 20h post-ovulation. The miRNA target validation assay revealed that miR-1764 and miR-1700 bind directly to SLC13A2 and SLC35B4 transcripts, respectively, to regulate expression. Collectively, these results indicate cell- and tissue specific expression of WNT4 and selected SLC genes in the reproductive tract of chickens. In addition, these genes are regulated by specific miRNAs. It is likely to have crucial roles in development and function of oviduct as well as initiation of ovarian carcinogenesis in laying hens.