Research Projects

MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression post-transcriptionally by binding to the 3’UTR of targeted mRNA. They are involved in several physiological and pathological processes, including reproductive and endocrine function. miRNA-106a-5p is a mature miRNA derived from the precursor miR-106a, which is part of the miR-17 family cluster. miRNA-106a-5p has gained attention due to its extensive role in various biological processes such as cell proliferation, differentiation, apoptosis, migration, and metabolism. Its dysregulation has been consistently observed across a range of human diseases, particularly in different types of cancers, where it can act as either an oncogene in colorectal cancer or a tumor suppressor in renal cell carcinoma. Therefore, this study aims to investigate the specific role of miRNA-106a-5p in the contribution to early age infertility (EAI) and polycystic ovary syndrome (PCOS) pathogenesis. Early age infertility refers to infertility in younger age, while PCOS is the most prevalent ovulation disorder in females of childbearing age. miRNA-106a-5p modulates the expression of target mRNAs through its downstream targets, for example STAT3 (signal transducer and activator of transcription 3) is a transcription factor that regulates cell migration, proliferation, invasion, and inflammation. PTEN (phosphatase and tensin homolog) is a tumor suppressor gene that regulates cell growth and survival through the PI3K/Akt signaling pathway. FOXC1 (forkhead box protein C1) is another downstream gene of miRNA-106a-5p, which regulates cell development and differentiation and is also associated with PI3K/Akt/mTOR signaling pathway. Therefore, it can be hypothesized that aberrant expression of miRNA-106a-5p through modulation of its key downstream targets may contribute to the hormonal imbalances, impaired folliculogenesis, and ovarian dysfunction, which may consequently lead to fertility issues in young women. This will be an in vivo study on female Wistar rats covering their early and post-pubertal periods and molecular validation techniques, including hormone assays, metabolic parameters, histopathology, inflammatory responses, miRNA-106a-5p expression, target gene identification, signaling pathway analysis, and its functional study, particularly miRNA-106a-5p mimic/inhibitor. Besides, this study will seek to explain the precise action mechanisms of miRNA-106a-5p influencing gonadal function. This study further advances in understanding the molecular mechanism and implications of early age infertility and the pathogenesis of PCOS. We may expect that changes in circulating miRNA-106a-5p levels would serve as a non-invasive biomarker for reproductive health issues. Further, the findings may pave the way for developing miRNA-targeted therapeutic strategies to mitigate reproductive and fertility issues and for improved patient management.

Endocrine disrupting chemicals, Reproductive toxicity, Infertility, Steroidogenesis, Polycystic ovary