MicroRNA in the ovary and female reproductive tract

Abstract

Posttranscriptional gene regulation plays a vital role in male and female germ cell function, but our understanding of this regulatory process in somatic cells and its effect on reproductive tissue development and function is not understood. In mammalian cells, microRNA (miRNA) are key posttranscriptional regulators and function by modulating translation or degradation of their target mRNA. Mature miRNA are synthesized through a multi-step process that concludes with the cleavage of stem-loop pre-miRNA by the RNase III enzyme, Dicer1. To determine the extent of miRNA regulation and establish a baseline, miRNA profiling has indicated the presence of large numbers of miRNA within reproductive tissues and cells. Moreover, several studies have indicated that miRNA expression in reproductive tissues varies in response to pituitary and gonadal hormones. To understand the role that miRNA-mediated posttranscriptional gene regulation plays in female reproduction, a global Dicer1 hypomorph mouse and several tissue-specific Dicer1 knockout mice have been studied. Interestingly, when Dicer1 expression is decreased in reproductive tissues or cells, the females are infertile. This review discusses all the work regarding miRNA regulation within the mammalian female reproductive system published to date.

Figure 1

Working model of miRNA biogenesis and function. Within the nucleus, microRNAs (miRNAs) are transcribed by RNA polymerase II (Pol-II) into single strand RNA which folds into a double stranded primary miRNA (pri-miRNA). Pri-miRNAs are subsequently bound in the cell nucleus by DiGeorge syndrome criticial region gene 8 (DGCR8) and then cleaved by Drosha yielding the precursor pre-miRNA. Pre-miRNAs are then transported from the nucleus via exportin-5 (Exp5) to the cytoplasm where they are further cleaved by the RNAse III endonuclease Dicer into a double-stranded miRNA. The double stranded miRNA separates into two single strands with one being degraded and the other strand forming a complex with Argonaute proteins, forming the RNA-inducing silencing complex (RISC). The RISC then binds to target mRNAs leading to either translational repression, translational enhancement, or transcript degradation.

Figure 2

Wild type (top) and Dicer1^fl/fl;Amhr2^Cre/+ (bottom) oviducts and ovaries and from immature age-matched mice. The Dicer1^fl/fl;Amhr2^Cre/+ oviducts are approximately one-third the length of the wild type and note the transparency of this tissue compared to the wild type particularly in the isthmus region due to a reduced/absent smooth muscle layer.