Potential Use of Antiapoptotic Proteins and Noncoding RNAs for Efficient In Vitro Follicular Maturation and Ovarian Bioengineering.

In vitro culture of ovarian follicles is a promising bioengineering technique for preserving fecundity in reproductive-aged female by providing fertilizable oocytes. Successful clinical application should be preceded by developing the protocols that can efficiently overcome follicular cell apoptosis since the apoptosis is a critical phenomenon in in vivo folliculogenesis and in in vitro follicular maturation. Numerous prosurvival and antiapoptotic molecules, including follicular developmental regulators, have been reported to be involved in the intraovarian apoptosis. The authors searched literature and analyzed the current knowledge of these proteins and noncoding RNAs, and their antiapoptotic roles in the dynamics of follicular development in vivo and in vitro. Two-dimensional (2D) culture method has widely been used, however, with recent emergence of various biomaterials, three-dimensional (3D) culture is also considered a proper environment for maintenance of solid structure of ovarian follicles. The identification of candidate paracrine and endocrine intracellular effectors that are responsible for the coordination occurring between oocyte, granulosa, and theca cells during follicular development was explored in this review, to assess the possibility of their use as antiapoptotic factors in establishing more efficacious 2D or 3D in vitro follicular microenvironment. The retrieved information will provide an inventory and the insight for defining more sophisticated culture conditions that are essential for functional artificial ovarian bioengineering.