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Hypoglycosylated FSH enhances oocyte quality via increased cell-to-cell interaction during mouse follicle development

ABSTRACT: Differences in follicle-stimulating hormone (FSH) ß-subunit N-glycosylation results in distinct FSH glycoforms. Hypoglycosylated FSH21 is more bioactive and abundant in reproductively young women, whereas fully glycosylated FSH24 shows lower bioactivity and a relative increase with age. To investigate if the coinciding shift in FSH glycoform abundance contributes to the age-dependent decline in oocyte quality, an encapsulated in vitro follicle growth system was utilized to examine the direct effects of FSH glycoforms on folliculogenesis and resulting oocyte quality. Long-term culture (10-12 days) with FSH21 (10 ng/ml) enhanced follicle growth, estradiol secretion, and oocyte quality compared to equivalent FSH24 treatment. FSH21 exhibited enhanced capacity to establish transzonal projections, gap junctions, and cell-to-cell communication within 24 hrs in culture. Transient inhibition of FSH21-mediated bidirectional communication abrogated the positive effects of FSH21 on follicle growth, estradiol secretion and oocyte quality. These findings indicate FSH21 promotes folliculogenesis and oocyte quality in vitro through increasing cell-to-cell communication early in folliculogenesis and that the shift in abundance from FSH21 to FSH24 with reproductive aging could contribute to the age-dependent decline in oocyte quality.

ORGANISM(S): Mus musculus

PROVIDER: GSE236967 | GEO | 2023/07/15

REPOSITORIES: GEO

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Project description:Background: With the rapid development of assisted reproductive technology (ART), although ovulation induction has made great progress, the accompanying health risks should not be ignored. Epigenetic modifications play an important role during the development of gametes and embryos. Recently, the epigenetic abnormalities caused by superovulation have attracted increasing attention. The follicle-stimulating hormone (FSH) and human menopausal gonadotropin (hMG) are common gonadotropins used for superovulation and appropriate concentration of them might be necessary. However, there is still no systematic study on the similarities and differences of DNA methylation alterations induced by superovulation with different dosage of FSH/hMG at the single cell levels. Methods: In the current study, the different doses of FSH/hMG combined with (add hcg full name here) hCG were used in C57BL/6 strain female mice to get experimental group oocytes while naturally matured oocytes and superovulated oocytes with only hCG were respectively set as controls. Single-cell level DNA methylation sequencing was carried out to all the mature oocytes to investigate the effect of superovulation with different dosage of FSH/hMG on DNA methylation during oocyte maturation. Results: In this study, we found that the hypo differentially methylated regions (DMRs) number of FSH/hMG 200 IU group both increased significantly although the whole genome methylation pattern of mature oocytes derived from superovulation were unaffected as compared with the control matured oocytes, suggesting that high dosage of FSH/hMG might lead to increased genomic methylation instability. At the same time, some of the DMRs annotated genes related to oocyte quality and embryonic development potential were disturbed in all dosage of FSH/hMG group (including Twist2, Cdk1, Ntrk2, Slc22a4, Sstr2, Wnt2, Cntnap5a, Gm2087, Slc16a7, and so on) as well as the certain ones (containing Abcc3, Zfp532, Atp1a1, Zfp804a, and so on) were impaired after high dosage of gonadotropins. We speculated that the effect of superovulation on DNA methylation during oocyte maturation might be dose-dependent to a certain extent, and such effect might affect oocyte quality and embryonic development competency. Conclusions: The current study firstly analyzed the differential impacts of different doses of gonadotropins on single-cell level DNA methylation of mouse oocytes, indicating a dose-dependent effect of superovulation with FSH/hMG and hCG on the epigenetic variations in mouse oocytes. Furthermore, some important genes that play a critical role in oocyte quality and embryo development were indicated to form the possible molecular basis of the corresponding regulation. This study laid a foundation for evaluating the safety of superovulation and highlighted the need for more and further research into ART.

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Hypoglycosylated FSH enhances oocyte quality via increased cell-to-cell interaction during mouse follicle development

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