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Does Pten have an impact on oogenesis of PCOS mouse models?

Published online by Cambridge University Press:  19 December 2022

T. Onal ,
P. Tulay Open the ORCID record for P. Tulay [Opens in a new window]  and
H.S. Vatansever
T. Onal
Affiliation:
Manisa Celal Bayar University, Faculty Medicine, Department of Histology and Embryology, Manisa, Turkey
P. Tulay*
Affiliation:
Near East University, Faculty of Medicine, Department of Medical Genetics, Nicosia, Cyprus Near East University, DESAM Research Institute, Nicosia, Cyprus
H.S. Vatansever
Affiliation:
Manisa Celal Bayar University, Faculty Medicine, Department of Histology and Embryology, Manisa, Turkey Near East University, DESAM Research Institute, Nicosia, Cyprus
*
Author for correspondence: Pinar Tulay, Near East University, Faculty of Medicine, Department of Medical Genetics; Near East University, DESAM Research Institute, Nicosia, Cyprus; Near East Boulevard, Nicosia North, Cyprus. E-mail: pinar.tulay@neu.edu.tr
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Summary

Polycystic ovary syndrome (PCOS) is a complex disorder in which the aetiology is still not explained very well. The PI3K/PTEN (phosphatidylinositol 3-kinase/phosphatase and tensin homolog deleted on chromosome 10) pathway is an important pathway that is involved in many mechanisms, including proliferation, growth and motility. PTEN plays a role in granulosa cell proliferation and regulates the differentiation process. The aim of this study was to investigate the expression levels of Pten and Pik3ca in PCOS mouse models with and without any treatment procedures. Three groups of mouse models, PCOS, a PCOS group with clomiphene citrate treatment, and a PCOS group with the combination of clomiphene citrate, metformin and pioglitazone treatment, were established. Ovarian tissues, which were obtained from these groups and a control group with no PCOS, were embedded in paraffin and RNA was extracted. cDNA was synthesized and real-time PCR was conducted to evaluate the expression levels of Pten and Pik3ca. The results of this study showed that both Pten and Pik3ca genes were expressed in the ovarian tissues from the mouse models. Although one-way analysis of variance results showed that Pten was expressed significantly differently in the samples, individual Student’s t-tests did not show any significantly different expression levels in each group. This study is important as it shows the expression patterns of two genes in PCOS mouse models with different treatment strategies, including clomiphene citrate, metformin and pioglitazone. The results of this study formed the basis of research studies and investigations into different genes within the PTEN pathway, as well as other pathways that are under investigation.

Keywords

Clomiphene citrateGene expressionMetforminPCOS mouse modelsPioglitazone treatmentPten
Type
Research Article
Information
Zygote , Volume 31 , Issue 1 , February 2023 , pp. 97 - 100
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Copyright
© The Author(s), 2022. Published by Cambridge University Press

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References

Adhikari, D., Gorre, N., Risal, S., Zhao, Z., Zhang, H., Shen, Y. and Liu, K. (2012). The safe use of a PTEN inhibitor for the activation of dormant mouse primordial follicles and generation of fertilizable eggs. PLOS ONE, 7(6), e39034. doi: 10.1371/journal.pone.0039034 CrossRefGoogle ScholarPubMed
Alam, H., Maizels, E. T., Park, Y., Ghaey, S., Feiger, Z. J., Chandel, N. S. and Hunzicker-Dunn, M. (2004). Follicle-stimulating hormone activation of hypoxia-inducible factor-1 by the phosphatidylinositol 3-kinase/AKT/Ras homolog enriched in brain (Rheb)/mammalian target of rapamycin (mTOR) pathway is necessary for induction of select protein markers of follicular differentiation. Journal of Biological Chemistry, 279(19), 19431–19440. doi: 10.1074/jbc.M401235200 CrossRefGoogle ScholarPubMed
Banerjee, S., Banerjee, S., Saraswat, G., Bandyopadhyay, S. A. and Kabir, S. N. (2014). Female reproductive aging is master-planned at the level of ovary. PLOS ONE, 9(5), e96210. doi: 10.1371/journal.pone.0096210 CrossRefGoogle ScholarPubMed
Gao, Y., Chen, J., Ji, R., Ding, J., Zhang, Y. and Yang, J. (2021). USP25 regulates the proliferation and apoptosis of ovarian granulosa cells in polycystic ovary syndrome by modulating the PI3K/AKT pathway via deubiquitinating PTEN. Frontiers in Cell and Developmental Biology, 9, 779718. doi: 10.3389/fcell.2021.779718 CrossRefGoogle ScholarPubMed
Goto, M., Iwase, A., Ando, H., Kurotsuchi, S., Harata, T. and Kikkawa, F. (2007). PTEN and Akt expression during growth of human ovarian follicles. Journal of Assisted Reproduction and Genetics, 24(11), 541–546. doi: 10.1007/s10815-007-9156-3 CrossRefGoogle ScholarPubMed
Goto, M., Iwase, A., Harata, T., Takigawa, S., Suzuki, K., Manabe, S. and Kikkawa, F. (2009). IGF1-induced AKT phosphorylation and cell proliferation are suppressed with the increase in PTEN during luteinization in human granulosa cells. Reproduction (Cambridge, England), 137(5), 835–842. doi: 10.1530/REP-08-0315 CrossRefGoogle ScholarPubMed
He, T., Liu, Y., Zhao, S., Liu, H., Wang, Z. and Shi, Y. (2019). Comprehensive assessment the expression of core elements related to IGFIR/PI3K pathway in granulosa cells of women with polycystic ovary syndrome. European Journal of Obstetrics, Gynecology, and Reproductive Biology, 233, 134–140. doi: 10.1016/j.ejogrb.2018.12.010 CrossRefGoogle ScholarPubMed
Iwase, A., Goto, M., Harata, T., Takigawa, S., Nakahara, T., Suzuki, K., Manabe, S. and Kikkawa, F. (2009). Insulin attenuates the insulin-like growth factor-I (IGF-I)-Akt pathway, not IGF-I-extracellularly regulated kinase pathway, in luteinized granulosa cells with an increase in PTEN. Journal of Clinical Endocrinology and Metabolism, 94(6), 2184–2191. doi: 10.1210/jc.2008-1948 CrossRefGoogle Scholar
Jagarlamudi, K., Liu, L., Adhikari, D., Reddy, P., Idahl, A., Ottander, U., Lundin, E. and Liu, K. (2009). Oocyte-specific deletion of Pten in mice reveals a stage-specific function of PTEN/PI3K signaling in oocytes in controlling follicular activation. PLOS ONE, 4(7), e6186. doi: 10.1371/journal.pone.0006186.CrossRefGoogle ScholarPubMed
Kauffman, A. S., Thackray, V. G., Ryan, G. E., Tolson, K. P., Glidewell-Kenney, C. A., Semaan, S. J., Poling, M. C., Iwata, N., Breen, K. M., Duleba, A. J., Stener-Victorin, E., Shimasaki, S., Webster, N. J. and Mellon, P. L. (2015). A novel letrozole model recapitulates both the reproductive and metabolic phenotypes of polycystic ovary syndrome in female mice. Biology of Reproduction, 93(3), 69. doi: 10.1095/biolreprod.115.131631 CrossRefGoogle ScholarPubMed
Li, J., Kawamura, K., Cheng, Y., Liu, S., Klein, C., Liu, S., Duan, E. K. and Hsueh, A. J. (2010). Activation of dormant ovarian follicles to generate mature eggs. Proceedings of the National Academy of Sciences of the United States of America, 107(22), 10280–10284. doi: 10.1073/pnas.1001198107 CrossRefGoogle ScholarPubMed
Markholt, S., Grøndahl, M. L., Ernst, E. H., Andersen, C. Y., Ernst, E. and Lykke-Hartmann, K. (2012). Global gene analysis of oocytes from early stages in human folliculogenesis shows high expression of novel genes in reproduction. Molecular Human Reproduction, 18(2), 96–110. doi: 10.1093/molehr/gar083 CrossRefGoogle ScholarPubMed
McNatty, K. P., Reader, K., Smith, P., Heath, D. A. and Juengel, J. L. (2007). Control of ovarian follicular development to the gonadotrophin-dependent phase: A 2006 perspective. Society of Reproduction and Fertility Supplement, 64, 55–68. doi: 10.5661/rdr-vi-55 Google Scholar
Ouyang, J. X., Luo, T., Sun, H. Y., Huang, J., Tang, D. F., Wu, L., Zheng, Y. H. and Zheng, L. P. (2013). RNA interference mediated Pten knock-down inhibit the formation of polycystic ovary. Molecular and Cellular Biochemistry, 380(1–2), 195–202. doi: 10.1007/s11010-013-1673-z CrossRefGoogle ScholarPubMed
Reddy, P., Shen, L., Ren, C., Boman, K., Lundin, E., Ottander, U., Lindgren, P., Liu, Y. X., Sun, Q. Y. and Liu, K. (2005). Activation of AKT (PKB) and suppression of FKHRL1 in mouse and rat oocytes by stem cell factor during follicular activation and development. Developmental Biology, 281(2), 160–170. doi: 10.1016/j.ydbio.2005.02.013 CrossRefGoogle ScholarPubMed
Reddy, P., Liu, L., Adhikari, D., Jagarlamudi, K., Rajareddy, S., Shen, Y., Du, C., Tang, W., Hämäläinen, T., Peng, S. L., Lan, Z. J., Cooney, A. J., Huhtaniemi, I. and Liu, K. (2008). Oocyte-specific deletion of Pten causes premature activation of the primordial follicle pool. Science, 319(5863), 611–613. doi: 10.1126/science.1152257 CrossRefGoogle ScholarPubMed
Tulay, P., Naja, R. P., Cascales-Roman, O., Doshi, A., Serhal, P. and SenGupta, S. B. (2015). Investigation of microRNA expression and DNA repair gene transcripts in human oocytes and blastocysts. Journal of Assisted Reproduction and Genetics, 32(12), 1757–1764. doi: 10.1007/s10815-015-0585-0 CrossRefGoogle ScholarPubMed
Tulay, P., Onal, T. and Vatansever, S. (2022). Molecular regulation of polycystic ovary syndrome: altered gene expression levels in mouse models pretreatment and post-treatment. Zygote (Cambridge, England), 30(3), 352–357. doi: 10.1017/S0967199421000769 CrossRefGoogle ScholarPubMed
Untergasser, A., Cutcutache, I., Koressaar, T., Ye, J., Faircloth, B. C., Remm, M. and Rozen, S. G. (2012). Primer3 – New capabilities and interfaces. Nucleic Acids Research, 40(15), e115. doi: 10.1093/nar/gks596 CrossRefGoogle ScholarPubMed