Context: Tissue-specific dicer1 knockout female mice display severe and irreversible damage to the Fallopian tubes that eventually leads to disruption of tubal transport of the gametes and the early embryo. The impact of Dicer1 on the function of human Fallopian tubes remains to be clarified.
Objective: To determine how the expression of tubal Dicer1 is regulated in women during the ovulatory process and in the mid-secretory phase. Furthermore, the association between tubal Dicer1 expression and alterations in estrogen receptor (ER) subtype and progesterone receptor (PR) isoform expression was investigated.
Research design and methods: The three phases of the ovulatory process was defined as followed: (1) the early ovulatory phase (n=4); (2) the late ovulatory phase (n=4); and (3) the post-ovulatory phase (n=5). The mid-secretory phase (n=4) was determined by the last menstrual period and endometrial histology. Serum was obtained immediately before surgery to confirm the ovulatory and mid-secretory phase categories. Localization and regulation of Dicer1, ER subtypes, and PR isoforms were determined by immunofluorescence, confocal microscopy and quantitative RT-PCR. Correlations were evaluated by bivariate Pearsons correlation coefficients.
Results: Dicer1 protein expression was most abundant in epithelial cells of the Fallopian tubes. The expression levels of Dicer1 mRNA and protein were significantly higher in the late ovulatory phase than in other phases. Moreover, no significant relationship between stages in ER subtype and PR isoform mRNA levels was found during the ovulatory process; however, expression levels of ERβ1 and ERβ2 mRNA and protein were significantly lower in all phases of the ovulatory process compared to the mid-secretory phase. The opposite pattern was seen in the expression levels of PRA/B and PRB mRNA and protein. Dicer1 mRNA expression was positively correlated with expression of ERα mRNA in the late ovulatory phase and negatively correlated with expression of ERβ2 mRNA in the mid-secretory phase, as well as PRB mRNA in the early ovulatory phase.
Conclusion: This is the first study to identify the cell-specific upregulation of Dicer1 expression in human Fallopian tubes during the ovulatory process. While the regulation of steroid hormone receptors is well established, stage-dependent expression of Dicer1 and its correlation to ERα, ERβ2 and PRB mRNA suggest that tubal Dicer1 may participate in the regulation of tubal steroid hormone receptor expression in a cycle-dependent manner and may be an important contributor to the tubal transport process in humans.
Key words: Dicer, microRNA, steroid hormone receptor, Fallopian tube, human