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. 2023 Dec 13;13(1):e230343.
doi: 10.1530/EC-23-0343. Print 2024 Jan 1.

Mfn2 regulates mitochondria-associated ER membranes to affect PCOS oocyte development

Xiuhua Liao  1   2   3 , Suqin Zhu  1 , Shumin Qiu  1 , Hua Cao  1 , Wenwen Jiang  1 , Huiling Xu  1 , Yan Sun  1 , Beihong Zheng  1   2   3
Affiliations

Mfn2 regulates mitochondria-associated ER membranes to affect PCOS oocyte development

Xiuhua Liao et al. Endocr Connect. .

Abstract

This study aimed to investigate the role of mitochondrial-related protein Mfn2 in polycystic ovary syndrome (PCOS) and its impact on oocyte development. The pathological features of PCOS model mice were confirmed by hematoxylin-eosin staining and immunohistochemistry. The expression of Mfn2 and mitochondrial-related proteins in PCOS oocytes and granulosa cells was detected by qRT-PCR and Western blot. Mitochondrial quantity was measured by Mito-Tracker staining, and the structure of mitochondria-associated ER membranes (MAMs) was observed by transmission electron microscopy. The results showed that Mfn2 was significantly downregulated in PCOS oocytes and granulosa cells, and its expression was inhibited in oocytes at different developmental stages. Moreover, the structure of MAMs was also disrupted. Downregulation of Mfn2 expression led to a reduction in mitochondrial quantity in oocytes and granulosa cells, as well as disruption of MAM structure, while overexpression of Mfn2 had the opposite effect. In conclusion, this study indicates that Mfn2 affects the development of PCOS oocytes by regulating MAMs and may be involved in maintaining the stability of MAM structure and function, thereby affecting mitochondrial quantity and function. These findings provide new insights into the pathogenesis and treatment of PCOS.

Keywords: Mfn2; mitochondria-associated endoplasmic reticulum membranes; oocyte granulosa cells; polycystic ovary syndrome.

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Conflict of interest statement

The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the study reported.

Figures

Figure 1
Figure 1
Histological analysis of PCOS model. (A) HE staining of the ovaries, 100×; (B) HE staining of the ovaries, 200×. CL, corpus luteum; ANF, antral follicle; ATF, atretic follicle; CF, cystic follicle.
Figure 2
Figure 2
Protein abundance and gene expression in the PCOS mouse model. (A) Immunohistochemistry was applied to assess Mfn2 in ovarian tissue sections (200×). Mfn2 and mitochondrial-related protein expression in MAMs, including IPR3, DRP1, and VDAC, was analyzed by (B) qRT-PCR and (C) Western blot in the control group and model group (**P < 0.01, ***P < 0.001, compared with control).
Figure 3
Figure 3
The contents of Mfn2 in oocytes and granulosa cells at different developmental stages. Mfn2 in granulosa cells was detected by (A) qRT-PCR and (B, C) Western blot in the control group and model group. Mfn2 in oocytes at different stages was detected by (D) qRT-PCR and (E, F) Western blot in the control group and model group (*P < 0.05, **P < 0.01, ***P < 0.001, compared with control).
Figure 4
Figure 4
The effect of PCOS on mitochondrial quantity and distribution. (A) Mitochondrial distribution was visualized by Mito-Tracker staining in the oocytes and granulosa cells isolated from both groups of mice. (B) The interaction between ER and mitochondria was observed using TEM in the oocytes and granulosa cells. The red boxes present MAMs.
Figure 5
Figure 5
Validation of transfection in oocytes with Mfn2 overexpression vector or Mfn2 siRNA. Mfn2 in oocytes was detected by qRT-PCR in different transfection groups (***P < 0.001, compared with control).
Figure 6
Figure 6
The influence of Mfn-2 on mitochondrial quantity and distribution in oocytes and granulosa cells. (A) Mitochondrial quantity in oocytes and granulosa cells transfected with different miR-542 levels was demonstrated by mitochondrial tracking staining. (B) The situation of MAMs in oocytes and granulosa cells transfected with different miR-542 levels was observed through TEM. The red boxes present MAMs.
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References

    1. Norman RJ Dewailly D Legro RS & Hickey TE. Polycystic ovary syndrome. Lancet 2007370685–697. (10.1016/S0140-6736(0761345-2) - DOI - PubMed
    1. Borchers A & Pieler T. Programming pluripotent precursor cells derived from Xenopus embryos to generate specific tissues and organs. Genes 20101413–426. (10.3390/genes1030413) - DOI - PMC - PubMed
    1. Mantle D & Hargreaves IP. Coenzyme Q10 and endocrine disorders: an overview. Anti Oxidants 202312514. (10.3390/antiox12020514) - DOI - PMC - PubMed
    1. Dong XC Liu C Zhuo GC & Ding Y. Potential roles of mtDNA mutations in PCOS-IR: a review. Diabetes, Metabolic Syndrome and Obesity 202316139–149. (10.2147/DMSO.S393960) - DOI - PMC - PubMed
    1. Yang X Zhuang J Song W Shen W Wu W Shen H & Han S. Mitochondria-associated endoplasmic reticulum membrane: overview and inextricable link with cancer. Journal of Cellular and Molecular Medicine 202327906–919. (10.1111/jcmm.17696) - DOI - PMC - PubMed

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