The Joint Annual Scientific Meetings of the Endocrine Society of Australia and the Society for Reproductive Biology 2018

MicroRNA biogenesis machinery is dysregulated in the endometrium of infertile women suggesting a role in receptivity and infertility (#386)

Katarzyna Rainczuk , Evdokia Dimitriadis

Implantation failure is a major contributor of female infertility and a major cause of implantation failure is abnormal endometrial receptivity. Recent studies identified that there is a widespread alteration of small non-coding RNA, microRNAs (miRs) in infertile endometrium. We aimed to determine the gene expression and spatial and temporal immunolocalisation of the miR biogenesis molecules, Argonaut 1 and 2, Drosha and Dicer in endometrium.  

Human endometrium was collected from women with normal fertility and primary unexplained infertility across the menstrual cycle (proliferative, early-secretory (pre-receptive), mid-(receptive) and late-secretory tissue; N=6/group). RNA was isolated from tissue and primary endometrial stromal (HESC)(N=5/group) and epithelial cells(HEEC)(N=5/group) and the mRNA expression determined by real-time RT-PCR.  Protein production was determined by immunohistochemistry (N=6/group).

Drosha, Argonaut 1 and 2 mRNA were significantly reduced in endometrial tissue of women with infertility compared to fertile controls in pre-receptive and receptive phases respectively (P<0.01), while Dicer mRNA was not altered. By contrast, Drosha, Dicer, Argonaut 1 and 2 mRNA expression were not altered in primary HEEC and HESC isolated from infertile women compared to fertile controls respectively.

Immunohistochemistry for all 4 biogenesis machinery revealed that the staining intensity was maximal in the luminal (surface) and glandular epithelium and to a lesser extent to the stroma and vascular cells in the endometrium.  Drosha immunostaining intensity was reduced in the luminal epithelium and in the pre-receptive phase in infertile endometrium compared to fertile (P<0.01), while in the glandular epithelium and stroma Drosha was reduced in the glandular epithelium in the receptive phase in the infertile endometrium (P<0.01). 

This is the first study to reveal specific miR biogenesis machinery were dysregualted in the endometrium during receptivity and has identified a mechanism by which miR expression and their targets may be dysregualted in infertility and may therefore contribute to implantation failure and infertility.