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. 2017 Dec 12;12(12):e0187427.
doi: 10.1371/journal.pone.0187427. eCollection 2017.

Attenuated expression of MTR in both prenatally androgenized mice and women with the hyperandrogenic phenotype of PCOS

Lei Lei  1   2 , Lijun Ding  3 , Jing Su  3 , Mengyuan Liu  3 , Qingqing Shi  3 , Jianjun Zhou  3 , Haixiang Sun  1 , Guijun Yan  3
Affiliations

Attenuated expression of MTR in both prenatally androgenized mice and women with the hyperandrogenic phenotype of PCOS

Lei Lei et al. PLoS One. .

Abstract

Polycystic ovary syndrome (PCOS) is a common endocrine, metabolic and heterogeneous disorder in women of reproductive age, the exact etiology of which remains unknown. To unravel the molecular mechanisms underlying the hyperandrogenic phenotype of PCOS, prenatally androgenized (PNA) mice were used to mimic this phenotype in women with PCOS. Using microarray analysis, 1188 differentially expressed genes, including 671 upregulated and 517 downregulated genes, were identified in ovaries from PNA mice. Five differentially expressed genes (Aldh1a7, Bhmt, Mtr, Nrcam, Ptprg) were validated, and decreased MTR expression was shown in ovaries of PNA mice. In addition, results from qRT-PCR showed decreased MTR expression in granulosa cells (GCs) from women with the hyperandrogenic phenotype of PCOS. Serum levels of S-adenosyl methionine (SAM), the downstream product of MTR, were also decreased in PNA mice and women with the hyperandrogenic phenotype of PCOS. Our study provides evidence that the hyperandrogenic phenotype of PCOS is linked to abnormal folate one-carbon metabolism.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Estrous cycle, serum testosterone levels, ovarian morphology and follicles counting of mouse.
(A) Representative estrous cycles in control (Upper) and PNA mice (Lower) (M, metestrus; E, estrus; D, diestrus; P, proestrus). (B) T levels in diestrus mice. (C) (D) HE stained ovarian section of control mouse at 3 months. (E) (F) HE stained ovarian section of PNA mouse at 3 months. (G) Follicle counting at 3 months, numbers represent total counting of every fifth section from serially sectioned ovaries. (H) Proportion of follicles in each stage.(*: P< 0.05).
Fig 2
Fig 2. Microarrayanalysis and validation.
(A) Heatmap of microarray analysis. (B) -(F) Five differentially expressed genes were validated by qRT-PCR(B, Mtr; C, Aldh1a7; D, Bhmt; E, Nrcam; F, Ptprg).(*: P< 0.05).
Fig 3
Fig 3. Differentially expressed MTR in mice.
(A)–(D) Immunohistochemistry. (A) Negative control (ovary). (B) Positive control (pancreas). (C) Ovary of control mouse. (D) Ovary of PNA mouse. (E) IOD of MTR was significantly lower in PNA mice. (*: P< 0.05). (F) WB showed expression of MTR in ovaries of PNA mice decreased at 3 months age. (G) WB showed expression of MTR in ovaries of PNA mice decreased at 3 weeks age.
Fig 4
Fig 4. Differentially expressed MTR in women, serum SAM levels in mouse and women.
(A) PNA decreases serum SAM levels in mouse. (B) Women with PCOS have low- expressed MTR in GCs. (C) low- SAM level in serum of women with PCOS.(*: P< 0.05).
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References

    1. Azziz R. PCOS in 2015: New insights into the genetics of polycystic ovary syndrome. Nature reviews Endocrinology. 2016;12(3):183 doi: 10.1038/nrendo.2016.9 . - DOI - PubMed
    1. Legro RS, Driscoll D, Strauss JF 3rd, Fox J, Dunaif A. Evidence for a genetic basis for hyperandrogenemia in polycystic ovary syndrome. Proceedings of the National Academy of Sciences of the United States of America. 1998;95(25):14956–60. . - PMC - PubMed
    1. Sudo S, Kudo M, Wada S, Sato O, Hsueh AJ, Fujimoto S. Genetic and functional analyses of polymorphisms in the human FSH receptor gene. Molecular human reproduction. 2002;8(10):893–9. . - PubMed
    1. Lee EJ, Oh B, Lee JY, Kimm K, Lee SH, Baek KH. A novel single nucleotide polymorphism of INSR gene for polycystic ovary syndrome. Fertility and sterility. 2008;89(5):1213–20. doi: 10.1016/j.fertnstert.2007.05.026 . - DOI - PubMed
    1. Peral B, San Millan JL, Castello R, Moghetti P, Escobar-Morreale HF. Comment: the methionine 196 arginine polymorphism in exon 6 of the TNF receptor 2 gene (TNFRSF1B) is associated with the polycystic ovary syndrome and hyperandrogenism. The Journal of clinical endocrinology and metabolism. 2002;87(8):3977–83. doi: 10.1210/jcem.87.8.8715 . - DOI - PubMed

Grants and funding

This study was funded by the National Nature Science Foundation of China (81590391, 31590189, and 30900847), the Health Department of Jiangsu Province (LJ201102), the Natural Science Foundation of Jiangsu Province (BK20141087 and BL2014003), and the Nanjing Medical Science Development Project (JQ2014004 and ZKX16042), China.