Distinct Expression Pattern of Dicer1 Correlates with Ovarian-Derived Steroid Hormone Receptor Expression in Human Fallopian Tubes during Ovulation and the Midsecretory Phase

Abstract

Tissue-specific dicer1 knockout mice display severe, irreversible Fallopian tube damage and disrupted tubal transport. It is not known how Dicer1 affects human Fallopian tube function. The aim of the study was to investigate the regulation of tubal Dicer1 expression during ovulation and the midsecretory phase and to assess Dicer1-associated alterations in estrogen receptor (ER) subtype and progesterone receptor (PR) expression. Fallopian tissue was obtained from patients at early (n = 4), late (n = 4), and postovulatory (n = 5) phases and the midsecretory phase (n = 4). Serum was obtained immediately before surgery (sterilization or hysterectomy) to confirm the phases. The localization and regulation of Dicer1, ER subtypes, and PR isoforms were determined by immunofluorescence, confocal microscopy, and quantitative RT-PCR. Dicer1 protein was expressed most abundantly in Fallopian epithelial cells; mRNA and protein levels peaked in the late ovulatory phase. ER subtype and PR isoform mRNA levels were not related to ovulatory stages; however, ERβ1 and ERβ2 mRNA/protein levels were highest and PRA/B and PRB mRNA/protein levels were lowest in the midsecretory phase. Dicer1 mRNA expression correlated positively with ERα mRNA expression in the late ovulatory phase and negatively with ERβ2 mRNA expression in the midsecretory phase and PRB mRNA in the early ovulatory phase. Dicer1 expression is up-regulated in cell-specific fashion in human Fallopian tubes during ovulation. The stage-dependent expression of Dicer1 and its correlation with ERα, ERβ2, and PRB mRNA suggests that tubal Dicer1 helps regulate tubal expression of steroid hormone receptors in a cycle-dependent manner and may contribute to tubal transport in humans.