MiR-133b Regulates the Expression of the Actin Protein TAGLN2 during Oocyte Growth and Maturation: A Potential Target for Infertility Therapy

Guohong Xiao,Xiangjin Kang,Pengke Yan,Shengsong Tang,Yuyi Lin,Jie Yang,Chenglai Xia,Hongzi Du,Jianqiao Liu,Ronghua Guan,Shibo Jiang

doi:10.1371/journal.pone.0100751

Guohong Xiao, Xiangjin Kang + Show 9 more

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https://doi.org/10.1371/journal.pone.0100751

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Abstract

Infertility is an area of increasing in life science research. Although follicular maturation disorders and anovulation are the primary causations of infertility, its molecular mechanism is not well understood. Recent research has shown that microRNAs (miRNAs) might play an important role in the regulation of ovarian follicle development and maturation. In this study, the expression of miRNAs in metaphase I (MI) oocytes treated with or without insulin-like growth factor 1 (IGF-1) was observed by microRNA microarray analysis. Results show that 145 miRNAs were up-regulated and 200 miRNAs were down-regulated in MI oocytes after IGF-1 treatment. MiR-133b, which was up-regulated more than 30-fold, was chosen for further research. As a potential target of miR133b, transgelin 2 (TAGLN2) gene was down-regulated, at both transcription and translation levels, in miR-133b- over-expressed 293T cells, but TAGLN2 was up-regulated when the expression of miR-133b was inhibited. Furthermore, the expression level of TAGLN2 in the ovaries of 8-week- old mice was higher than that observed in 4-week-old mice. Immunofluorescence experiments showed that TAGLN2 was located in the cytoplasm. In general, our results indicate that miR-133b may play important roles in the growth and maturation of oocytes by regulating its potential target, TAGLN2, at both transcription and translation levels. Therefore, our research provides a potential new target for infertility therapy.

Highlights

For sustained and successful reproduction, proper development and function of the hypothalamic-pituitary-gonadal axis and its regulation of the cervical, uterine, and oviductal tissues are imperative
Pri-miR21 expression increased by 30 times in the theca cells of immature mice after 4 h of human chorionic gonadotropin stimulation, while miR-21 increased by 5.8 times after a 6 h hCG treatment in mature mice
Injecting miR-21-LNA into the ovarian bursa led to obvious change in the morphology of granulosa cells, and miR-21 expression was up-regulated, while the degradation of caspase-3 was reduced under luteinizing hormone (LH) treatment

Summary

Introduction

For sustained and successful reproduction, proper development and function of the hypothalamic-pituitary-gonadal axis and its regulation of the cervical, uterine, and oviductal tissues are imperative. It has been reported that miRNAs participate in the regulation of cell proliferation, differentiation, apoptosis, migration, tissue inflammation, tumor formation and energy metabolism at different levels, including transcription, translation, and posttranslation [1,2,3,4]. Dicer knockout oocytes led to the loss of oocyte meiotic spindle structure and chromosome condensation, in turn, resulting in the loss of meiotic division follicular developmental abnormalities, ovulation disorders, apoptosis and infertility [7,8,9]. Such dicer mutants indicate that miRNAs play important roles in fertility by regulating follicular and ovarian functions. In the granulosa cells, the tumor suppressor gene p53 and NF-kB p65 cooperated to inhibit miR-224 expression, resulting in the proliferation of granulosa cells and estradiol release [14]

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