MicroRNA in the ovary and female reproductive tract1

Abstract

Post-transcriptional 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 impact on reproductive tissue development and function is not understood. In mammalian cells, microRNA (miRNA) are key post-transcriptional 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 miRNA mediated post-transcriptional 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 reduced 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.

Expression of fragile X mental retardation protein and Fmr1 mRNA during folliculogenesis in the rat

“…Considering that FMRP is a major cellular translational repressor protein that binds to multiple transcripts thereafter controlling their translation rate (Laggerbauer et al 2001, Schaeffer et al 2001, Schuettler et al 2011, low amounts of the protein during the preantral stage could allow a more permissive translation of target mRNAs, while a progressive repressing state would be expected in developing follicles. As FMRP has been shown to interact with miRNA and the components of the miRNA pathway (Caudy et al 2002, Jin et al 2004, and considering that miRNAs have an important role in post-transcriptional gene regulation in the ovary and in the female reproductive tract in general (Fiedler et al 2008, Carletti & Christenson 2009, Christenson 2010, it seems natural to assign to the Fmr1 expression during folliculogenesis protein a crucial role in the adequate functioning of the gonad. Defects in regulatory control can lead to ovarian failure due to disruption of folliculogenesis, block of ovulation and corpus luteum insufficiency, among others (Carletti & Christenson 2009).…”

“…As FMRP has been shown to interact with miRNA and the components of the miRNA pathway (Caudy et al 2002, Jin et al 2004, and considering that miRNAs have an important role in post-transcriptional gene regulation in the ovary and in the female reproductive tract in general (Fiedler et al 2008, Carletti & Christenson 2009, Christenson 2010, it seems natural to assign to the Fmr1 expression during folliculogenesis protein a crucial role in the adequate functioning of the gonad. Defects in regulatory control can lead to ovarian failure due to disruption of folliculogenesis, block of ovulation and corpus luteum insufficiency, among others (Carletti & Christenson 2009). Moreover, ovarian follicle development largely depends on the proliferation of GCs.…”

Advancement in Molecular Genetics to understand the molecular reproduction of Livestock – follicular development

“…Recruitment of growing follicles, atresia, ovulation, and luteal tissue formation and regression are dynamically regulated events that regenerate on a cyclical basis in the ovary. These events involve dynamic changes in cellular growth, angiogenesis, steroidogenesis, cell cycle, and apoptosis and are accurately regulated at the endocrine and tissue levels (Carletti and Christenson, 2009). Deregulation in the regulatory network results in ovarian failure such as premature ovarian failure (POF) due to disruption of folliculogenesis, blockage of ovulation, and loss of oocytes via apoptosis (Yang et al, 2012).…”

Cell Biology Symposium: The role of microRNA in cell function1

“…Reduced expression of Dicer in females results in infertility (Carletti and Christenson, 2009). Females without Dicer exhibited disrupted oviductal and uterine development, as well as reduced ovarian function, as evidenced by a decreased ovulation rate and presence of oocytes being trapped within the luteinized follicles .…”

“…Misregulation of microRNA may lead to anovulatory states causing infertility and increased culling rates in livestock. Thus, Carletti and Christenson (2009) proposed that understanding how microRNA may affect gene regulation may allow for manipulation of reproductive efficiency and reduction in the occurrence of reproductive disorders.…”