Plk is a serine/threonine kinase, which was firstly identified in Drosophila as Polo mutant over 27 years ago (Sunkel & Glover, 1988). This kinase is well conserved from budding yeast (Cdc5) to Drosophila (polo), Xenopus (Plxs) and mammals (Plks) (de Carcer et al., 2011a). In mammalian cells, it has been reported that four Plk family members, from Plk1 to Plk4, are expressed and recently Plk5 has been characterized in the mouse and human cells (de Carcer et al., 2011a). Plks are key regulators for various cellular events during cell division including centrosome maturation, DNA checkpoint activation, mitotic entry, spindle assembly, and cytokinesis (Fig. 1) (Glover et al., 1998; Dai, 2005; Strebhardt & Ullrich, 2006).

Kim KH, et al. Clin Exp Reprod Med. 2014 Jun;41(2):47-61. http://dx.doi.org/10.5653/cerm.2014.41.2.47

Kim Y, et al. Clin Exp Reprod Med. 2012 Jun;39(2):58-67. http://dx.doi.org/10.5653/cerm.2012.39.2.58

Kim E, et al. Endocrinol Metab. 2014 Mar;29(1):40-47. http://dx.doi.org/10.3803/EnM.2014.29.1.40

Previously, we reported that Sebox is a new maternal effect gene (MEG) that is required for early embryo development beyond the two-cell (2C) stage because this gene orchestrates the expression of important genes for zygotic genome activation (ZGA). However, regulators of Sebox expression remain unknown. Therefore, the objectives of the present study were to use bioinformatics tools to identify such regulatory microRNAs (miRNAs) and to determine the effects of the identified miRNAs on Sebox expression. Using computational algorithms, we identified a motif within the 3′UTR of Sebox mRNA that is specific to the seed region of the miR-125 family, which includes miR-125a-5p, miR-125b-5p and miR-351-5p. During our search for miRNAs, we found that the Lin28a 3′UTR also contains the same binding motif for the seed region of the miR-125 family. In addition, we confirmed that Lin28a also plays a role as a MEG and affects ZGA at the 2C stage, without affecting oocyte maturation or fertilization. Thus, we provide the first report indicating that the miR-125 family plays a crucial role in regulating MEGs related to the 2C block and in regulating ZGA through methods such as affecting Sebox and Lin28a in oocytes and embryos.

Background: Aging has detrimental effects on the ovary, such as a progressive reduction in fertility and decreased hormone production, that greatly reduce the quality of life of women. Thus, the current study was undertaken to investigate whether human placenta-derived mesenchymal stem cell (hPD-MSC) treatment can restore the decreases in folliculogenesis and ovarian function that occur with aging. Methods: Acclimatized 52-week-old female SD rats were randomly divided into four groups: single hPD-MSC (5 × 10⁵) therapy, multiple (three times, 10-day intervals) hPD-MSC therapy, control (PBS), and non-treated groups. hPD-MSC therapy was conducted by tail vein injection into aged rats. The rats were sacrificed 1, 2, 3, and 5 weeks after the last injection. hPD-MSC tracking and follicle numbers were histologically confirmed. The serum levels of sex hormones and circulating miRNAs were detected by ELISA and qRT-PCR, respectively. TGF-β superfamily proteins and SMAD proteins in the ovary were detected by Western blot analysis. Results: We observed that multiple transplantations of hPD-MSCs more effectively promoted primordial follicle activation and ovarian hormone (E₂ and AMH) production than a single injection. After hPD-MSC therapy, the levels of miR-21-5p, miR-132-3p, and miR-212-3p, miRNAs associated with the ovarian reserve, were increased in the serum. Moreover, miRNAs (miR-16-5p, miR-34a-5p, and miR-191-5p) with known adverse effects on folliculogenesis were markedly suppressed. Importantly, the level of miR-145-5p was reduced after single- or multiple-injection hPD-MSC therapy, and we confirmed that miR-145-5p targets Bmpr2 but not Tgfbr2. Interestingly, downregulation of miR-145-5p led to an increase in BMPR2, and activation of SMAD signaling concurrently increased primordial follicle development and the number of primary and antral follicles. Conclusions: Our study verified that multiple intravenous injections of hPD-MSCs led to improved ovarian function via miR-145-5p and BMP-SMAD signaling and proposed the future therapeutic potential of hPD-MSCs to promote ovarian function in women at advanced age to improve their quality of life during climacterium.