Abstract
The wingless-type MMTV integration site family of proteins (WNTs) is highly conserved secreted lipid-modified signaling molecules that play a variety of pivotal roles in developmental events such as embryogenesis, tissue homeostasis and cell polarity. Although, of these proteins, WNT4 is known to be involved in genital development in fetuses of mammalian species, its role is unknown in avian species. Therefore, in this study, we investigated expression profiles, as well as hormonal and post-transcriptional regulation of WNT4 expression in the reproductive tract of female chickens. Results of this study demonstrated that WNT4 is most abundant in the stromal and luminal epithelial cells of the isthmus and shell gland of the oviduct, respectively. WNT4 is also most abundant in the glandular epithelium of the shell gland of the oviduct of laying hens at 3 h post-ovulation during the laying cycle. In addition, treatment of young chicks with diethylstilbestrol (DES, a synthetic estrogen agonist) stimulated WNT4 only in the glandular epithelial cells of the isthmus and shell gland of the oviduct. Moreover, results of our study demonstrated that miR-1786 influences WNT4 expression via specific binding sites in its 3′-UTR. On the other hand, our results also indicate that WNT4 is expressed predominantly in the glandular epithelium of cancerous ovaries, but not in normal ovaries of hens. Collectively, these results indicate cell-specific expression of WNT4 in the reproductive tract of chickens and that it likely has crucial roles in development and function of oviduct as well as initiation of ovarian carcinogenesis in laying hens.
Highlights
The chicken oviduct is well known as a model for research on hormone action, including effects of estrogen and progesterone [1]
Results of RT-PCR analysis indicated a high level of WNT4 mRNA expression in the isthmus and the shell gland as compared with the infundibulum and the magnum (Figure 1A)
The WNT4 mRNA was most abundant in stromal cells and luminal epithelia (LE) of the isthmus and the shell gland, respectively
Summary
The chicken oviduct is well known as a model for research on hormone action, including effects of estrogen and progesterone [1]. Formation of the tubular glands and differentiation of the epithelial cells including goblet and ciliated cells in the chicken oviduct are induced by estrogen [3]. WNT4 is a secretory signaling protein concerned with multiple processes in organ development including formation of kidney, mammary gland and adrenal gland, as well as sexual development in mammals [4]. The Wnt signaling pathway participates in folliculogenesis, luteogenesis and steroidogenesis of granulosa cells and in the regulatory processes of stromal cell proliferation and differentiation for survival and development of embryos within the uterine lumen [5]. The WNT4-FZD2 signaling pathway is activated by binding of estrogen to estrogen receptor alpha (ESR1) in the uterus [6] and in somatotrophs that produce growth hormone in the anterior pituitary gland of rodents [4]. The elevated expression of WNT4 is frequently observed in many breast cancer patients which implies that it’s aberrant expression leads to abnormal cell proliferation and breast cancer in women [7]
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