PAT1 homolog 2 (PATL2), encoding an RNA-binding protein, is a repressor involved in the translational regulation of maternal mRNAs during oocyte maturation. Previous studies have reported mutations inPATL2those led to female infertility with oocyte maturation arrest; however, the mechanisms by which mutations affected meiotic maturation remained unclear. Here, we identified several novel and recurrent mutations ofPATL2in patients with similar phenotype, and chose the missense mutation c.649 T>A p.Tyr217Asn inPATL2(PATL2^Y217N) as a typical to investigate the underlying mechanisms. We confirmed that this mutation disturbed oocyte maturation and observed morphological defects of large polar body, symmetrical division and abnormal spindle after microinjection of corresponding mutated mRNA. We further evaluated the effect of the PATL2^Y217Nmutation in 293T cells, and found this mutation decreased the ubiquitination level and degradation of PATL2. Then, abnormally increased PATL2 bound mRNAs of Mos, an upstream activator of mitogen activated protein kinase (MAPK), to regulate its translational activity and subsequently impaired MAPK signaling pathway and oocyte meiosis. These results dissented from the previous view thatPATL2mutations reduced their expression and highlight the role of PATL2 in translational regulation of Mos and its association with MAPK signaling pathway during oocyte meiotic maturation.

Heat shock protein 27 (Hsp27), a member of the small heat shock protein family, is an apoptosis regulator. Our previous proteomic study showed that Hsp27 mainly expressed in human oocyte, and that Hsp27 expression was downregulated in the ovaries derived from women with the polycystic ovary syndrome (PCOS), a well known endocrinal disorder with abnormal apoptotic activity and folliculogenesis. However, the exact effects of Hsp27 downregulation on oocyte development have not yet been clarified.

The use of long protocol during controlled ovarian stimulation for assisted reproduction attracts high dosage of gonadotropins. High dose of gonadotropins can be detrimental to oocyte development, which affects its quality and compromises the treatment outcome. Mild stimulation protocols that attract low dose gonadotropins could be useful alternative regimen to address such problems. This study evaluated the efficacy of low dose clomiphene citrate based protocol plus low dose gonadotropins on predicted normal responder patients who had unsuspected poor in vitro fertilization (IVF) result, following an initial stimulation with long gonadotropin-releasing hormone (GnRH) agonist protocol. This a retrospective study of 65 infertile women who underwent 130 cycles in our center from January 2011 to December 2014. The initial IVF cycle (Group 1) was treated with long GnRH-a protocol plus a high dose of gonadotropins (≥150 IU/d), while second IVF cycle (Group 2) had low dose clomiphene citrate based protocol plus low dose gonadotropins (75–112.5 IU/d). The rate of cumulative pregnancy/started cycle (9.2% [6/65] vs. 51% [33/65]; P < 0001) was significantly better in CC protocol than the long GnRH agonist protocol. The number of oocytes retrieved was also higher in CC protocol compared to the long protocol (7.26 ± 1.95 vs. 5.98 ± 1.31; P = 0.03). There was a lower number of patients without embryos (12.31% vs. 33.85%; p < 0.0001) in CC protocol than long protocol. This study showed a better cumulative pregnancy rate in the low dose CC based protocol. There was a higher number of oocytes retrieved after using a lower total dose of recombinant FSH in CC protocol. Thus, clomiphene treatment plus low dose rFSH can be an alternative option for such patients in second cycle stimulation instead of repeating long protocol regimen. Randomized controlled studies with larger number of patients will be needed for more accurate evidence.

Background: Studies have shown that chemotherapy and radiotherapy can cause premature ovarian failure and loss of fertility in female cancer patients. Ovarian cortex cryopreservation is a good choice to preserve female fertility before cancer treatment. Following the remission of the disease, the thawed ovarian tissue can be transplanted back and restore fertility of the patient. However, there is a risk to reintroduce cancer cells in the body and leads to the recurrence of cancer. Given the low success rate of current in vitro culture techniques for obtaining mature oocytes from primordial follicles, an artificial ovary with primordial follicles may be a good way to solve this problem. Methods: In the study, we established an artificial ovary model based on the participation of mesenchymal stem cells (MSCs) to evaluate the effect of MSCs on follicular development and oocyte maturation. P2.5 mouse ovaries were digested into single cell suspensions and mixed with bone marrow derived mesenchymal stem cells (BM-MSCs) at a 1:1 ratio. The reconstituted ovarian model was then generated by using phytohemagglutinin. The phenotype and mechanism studies were explored by follicle counting, immunohistochemistry, immunofluorescence, in vitro maturation (IVM), in vitro fertilization (IVF), real-time quantitative polymerase chain reaction (RT-PCR), and Terminal-deoxynucleotidyl transferase mediated nick end labeling(TUNEL) assay. Results: Our study found that the addition of BM-MSCs to the reconstituted ovary can enhance the survival of oocytes and promote the growth and development of follicles. After transplanting the reconstituted ovaries under kidney capsules of the recipient mice, we observed normal folliculogenesis and oocyte maturation. Interestingly, we found that BM-MSCs did not contribute to the formation of follicles in ovarian aggregation, nor did they undergo proliferation during follicle growth. Instead, the cells were found to be located around growing follicles in the reconstituted ovary. When theca cells were labeled with CYP17a1, we found some overlapped staining with green fluorescent protein(GFP)-labeled BM-MSCs. The results suggest that BM-MSCs may participate in directing the differentiation of theca layer in the reconstituted ovary. Conclusions: The presence of BM-MSCs in the artificial ovary was found to promote the survival of ovarian cells, as well as facilitate follicle formation and development. Since the cells didn’t proliferate in the reconstituted ovary, this discovery suggests a potential new and safe method for the application of MSCs in clinical fertility preservation by enhancing the success rate of cryo-thawed ovarian tissues after transplantation.

We found previously that the expression of SET gene was up-regulated in polycystic ovaries. Evidences suggested that SET protein was essential for regulating both the promoter activity of CYP17A1 and the biological activity of P450c17. In this study, we explored whether SET regulated androgen production in preantral follicles.