YTHDF2 regulates MSS51 expression contributing to mitochondria dysfunction of granulosa cells in polycystic ovarian syndrome patients.

RESEARCH QUESTION: Granulosa cells (GCs) dysfunction plays a crucial role in the pathogenesis of polycystic ovary syndrome (PCOS). It is reported that YTH domain-containing family protein 2 (YTHDF2) is upregulated in mural GCs of PCOS patients. What effect does the differential expression of YTHDF2 have in PCOS patients? DESIGN: Mural GCs and cumulus GCs from 15 patients with PCOS and 15 ovulatory controls and 4 cases of pathological sections in each group were collected. Real-time PCR, Western Blot, immunohistochemistry, and immunofluorescence experiments were conducted to detect gene and protein expression. RNA immunoprecipitation assay was performed to evaluate the binding relationship between YTHDF2 and MSS51. Mitochondrial morphology, cellular ATP and ROS levels and glycolysis-related gene expression were detected after YTHDF2 overexpression or MSS51 inhibition. RESULTS: In the present study, we found that YTHDF2 was upregulated in GCs of PCOS patients while MSS51 was downregulated. YTHDF2 protein can bind to MSS51 mRNA and affect MSS51 expression. The reduction of MSS51 expression or the increase in YTHDF2 expression can lead to mitochondrial damage, reduced ATP levels, increased ROS levels and reduced expression of LDHA, PFKP and PKM. CONCLUSIONS: YTHDF2 may regulate the expression of MSS51, affecting the structure and function of mitochondria in GCs and interfering with cellular glycolysis, which may disturb the normal biological processes of GCs and follicle development in PCOS patients.

Comparative study on the pregnancy outcomes of in vitro fertilization-embryo transfer between patients with different ovarian responses (a STROBE-compliant article).

There have been few studies on large-sample data of cleavage-stage embryo and blastocyst transfers. We compared the pregnancy outcomes of patients with different ovarian responses after the transfer of different numbers of embryos in different developmental stages.Patients were divided into 3 groups including low response group, medium response group, and high response group according to different ovarian responses. Patients in each group were further divided into 4 subgroups including group A: transfer of 1 D3 embryo, group B: transfer of 2 D3 embryos; group C: transfer of 1 D5 blastocyst; and group D: transfer of 2 D5 blastocysts.In low ovarian responders, the implantation rate, clinical pregnancy rate and live birth rate were significantly lower in the group A than in the groups B and C. In medium ovarian responders, the implantation rate was significantly higher, but the multiple pregnancy rate was significantly lower in the group C than in the group B. The multiple pregnancy rate was significantly higher in the group D than in the group C. In high ovarian responders, the implantation rate was significantly lower, but the multiple pregnancy rate was significantly higher in the group B than in group C.Based on the above results, the single blastocyst transfer is preferable for the patients with different ovarian responses.