Increased N6‐methyladenosine causes infertility is associated with FTO expression

Abstract

The N6-methyladenosine (m6A) modification plays a central role in epigenetic regulation of the mammalian transcriptome. m6A can be demethylated by the fat mass- and obesity-associated (FTO) protein and the α-ketoglutarate-dependent dioxygenase alkB homolog 5 (ALKBH5) protein. Much less is known about that whether m6A content is involved in POI (premature ovarian insufficiency) disease. In this case-controlled study, 69 POI and 53 tubal occlusion patients were recruited from the reproduction centers in our hospital. For the POI animal model experiment, ovarian tissue was obtained from ten POI and nine healthy mice. An m6A test kit was developed to determine the m6A content in the RNA, and qPCR and western blot were used to examine the mRNA and protein expression levels of FTO and ALKBH5. FACS was used to measure the levels of proliferation and apoptosis, and siRNA was used to establish FTO and ALKBH5 knockdown cell lines. Our results showed that the m6A content in the RNA from POI patients and POI mice was significantly higher than control groups and that POI was characterized by the content of m6A. The mRNA and protein expression levels of FTO were significantly lower in the POI patients than control group and were associated with a risk of POI. These data suggest that the decreased mRNA and protein expression levels of FTO may be responsible for the increase in m6A in POI, which may further increase the risk of complications of POI. High m6A should be investigated further as a novel potential biomarker of POI.

Identification of a three-m6A related gene risk score model as a potential prognostic biomarker in clear cell renal cell carcinoma

“…Currently, as the importance of m6A cut a striking figure, despite the fact that the first report of m6A was as early in 1974 (Desrosiers, Friderici & Rottman, 1974), it was not until recent days that the mechanism of the m6A was uncovered (Roundtree et al, 2017). Moreover, plenty of researches has disclosed the associations of m6A modification in former mentioned cancerous diseases (Lobo et al, 2019;Taketo et al, 2018;Barbieri et al, 2017;Nishizawa et al, 2018) or non-cancerous diseases such as type 2 diabetes mellitus (Bohnsack & Sloan, 2018), and infertility (Ding et al, 2018), thus, we decided to build an RS model found on m6A genes. In our study, by using TCGA dataset, 12 DEGs were first screened out of 17 m6A related genes, within which we further found seven genes that showed potential significance in prognostic value.…”

The Effect of Huyang Yangkun Formula on N6-methyladenosine Modification in 4-vinylcyclohexene diepoxide Induced Premature Ovarian Insufficiency Rats

“…One study has reported that after inhibiting the activity of FTO, the proliferation of mouse spermatogonia cells was decreased (Huang et al, 2019). In addition, a case-controlled study showed that the FTO protein expression level was significantly lower in POI patients than in normal people (Ding et al, 2018).…”

Human Amniotic Fluid Mesenchymal Stem Cells Improve Ovarian Function During Physiological Aging by Resisting DNA Damage

“…Menopause is an inevitable stage during ovarian aging (Herbert et al, 2015). The growing primordial follicle pool serves as the initial source of developing follicles during stages of meiosis, but it mirrors the lifetime of ovaries in mice, suffering an inevitable decline with increasing age (Ding et al, 2018a).…”