Long noncoding RNA H19 in ovarian biology and placenta development.

As the first long noncoding RNA to be discovered, H19 has gained substantial attention as a key regulator of several biological processes and its roles in female reproductive biology are gradually getting revealed. Herein, we have summarized the current evidence regarding H19 expression pattern and involvement in the developmental and pathological processes associated with the ovary and the placenta. The findings indicate that within the ovaries, H19 is expressed in the antral and cystic atretic follicles as well as in the corpora lutea but absent in the primordial, primary, and secondary follicles. Its normal expression promotes the maturation of antral follicles and prevents their premature selection for the ovulatory journey while its aberrant induction promotes polycystic ovary syndrome development and ovarian cancer metastasis. In the placenta, H19 is highly expressed in the cytotrophoblasts and extravillous trophoblasts but weakly expressed in the syncytiotrophoblast layer and potentially controls trophoblast cell fate decisions during placenta development. Abnormal expression of H19 is observed in the placental villi of pregnancies affected by pre‐eclampsia and fetal growth restriction. Therefore, dysregulated H19 is a candidate biomarker and therapeutic target for the mitigation of ovarian and placenta‐associated diseases. Significance statement: We have proposed mechanisms by which H19 facilitates antral follicle maturation and placenta development as well as how H19 upregulation promotes epithelial ovarian cancer metastasis. We hope that therapeutic inhibition of this mechanism in the ovarian microenvironment can help mitigate epithelial ovarian cancers in both drug‐resistant and nondrug resistant patients. We have proposed serum H19 level as a potential biomarker for the clinical assessment of ovarian reserve. The future research directions and the ideal experimental approaches we have highlighted will help discover more reliable information about H19 actions in the female reproductive system. [ABSTRACT FROM AUTHOR]