Skip to main content
Log in

Dynamic methylation pattern of cyp19a1a core promoter during zebrafish ovarian folliculogenesis

  • Published:
Fish Physiology and Biochemistry Aims and scope Submit manuscript

Abstract

In vertebrates, the aromatase coded by the cyp19a1a gene can catalyze the conversion from androgens to estrogens. Thus, the regulatory mechanisms of cyp19a1a gene expression are a critical research field in reproductive endocrinology. In this study, we use zebrafish as a model to study the dynamic methylation levels of the cyp19a1a gene core promoter during zebrafish ovarian folliculogenesis. The results show that there is an apparent fluctuation of the methylation levels of zebrafish cyp19a1a core promoter. Moreover, the methylation levels are inversely correlated with the expression levels of cyp19a1a transcripts when the ovarian follicles develop from PV into the MV stage. Also, the CpG dinucleotides which are close to the transcriptional starting site may have provided a significant blocking effect on inhibiting the transcriptional function of RNA polymerase II. Taken together, the results from the present study strongly suggest that DNA methylation was one of mechanisms that are involved in the regulation of cyp19a1a gene expression during folliculogenesis. This methylation mechanism modifying transcriptional process accompanied with zebrafish ovarian folliculogenesis might also shed new light on the regulation of cyp19a1a expression during the ovarian developmental stage in other vertebrates.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  • Chiang E, Yan Y, Guiguen Y (2001) Two Cyp19 (P450 aromatase) genes on duplicated zebrafish chromosomes are expressed in ovary or brain. Mol Biol Evol 18:542–550

    Article  CAS  PubMed  Google Scholar 

  • Duffy T, Picha M, Won E, Borski R, McElroy A, Conover D (2010) Ontogenesis of gonadal aromatase gene expression in Atlantic silverside (Menidia menidia) populations with genetic and temperature-dependent sex determination. J Exp Zool 313A:421–431

    Article  CAS  Google Scholar 

  • Fürbass R, Selimyan R, Vanselow J (2008) DNA methylation and chromatin accessibility of the proximal Cyp19 promoter region 1.5/2 correlate with expression levels in sheep placentomes. Mol Reprod Dev 75:1–7

    Article  PubMed  Google Scholar 

  • Guengerich FP (2007) Cytochrome p450 and chemical toxicology. Chem Res Toxicol 21:70–83

    Article  PubMed  Google Scholar 

  • Kagawa H, Gen K, Okuzawa K (2003) Effects of luteinizing hormone and follicle-stimulating hormone and insulin-like growth factor-I on aromatase activity and P450 aromatase gene expression in the ovarian follicles of red seabream, Pagrus major. Biol Reprod 68:1562–1568

    Article  CAS  PubMed  Google Scholar 

  • Knower KC, To SQ, Simpson ER (2010) Epigenetic mechanisms regulating CYP19 transcription in human breast adipose fibroblasts. Mol Cell Endocrinol 321:123–130

    Article  CAS  PubMed  Google Scholar 

  • Kwok H-F, So W-K, Wang Y, Ge W (2005) Zebrafish gonadotropins and their receptors: I. Cloning and characterization of zebrafish follicle-stimulating hormone and luteinizing hormone receptors—evidence for their distinct functions in follicle development. Biol Reprod 72:1370–1381

    Article  CAS  PubMed  Google Scholar 

  • Lee L, Asada H, Kizuka F (2012) Changes in histone modification and DNA methylation of the StAR and Cyp19a1 promoter regions in granulosa cells undergoing luteinization during ovulation in rats. Endocrinology 154:458–470

    Article  PubMed  Google Scholar 

  • Lubzens E, Young G, Bobe J, Cerdà J (2010) Oogenesis in teleosts: how fish eggs are formed. Gen Comp Endocrinol 165:367–389

    Article  CAS  PubMed  Google Scholar 

  • Monga R, Ghai S, Datta TK (2011) Tissue-specific promoter methylation and histone modification regulate CYP19 gene expression during folliculogenesis and luteinization in buffalo ovary. Gen Comp Endocrinol 173:205–215

    Article  CAS  PubMed  Google Scholar 

  • Montserrat N, González A, Méndez E, Piferrer F, Planas JV (2004) Effects of follicle stimulating hormone on estradiol-17β production and P-450 aromatase (CYP19) activity and mRNA expression in brown trout vitellogenic ovarian follicles in vitro. Gen Comp Endocrinol 137:123–131

    Article  CAS  PubMed  Google Scholar 

  • Nakamura I, Evans JC, Kusakabe M, Nagahama Y, Young G (2005) Changes in steroidogenic enzyme and steroidogenic acute regulatory protein messenger RNAs in ovarian follicles during ovarian development of rainbow trout (Oncorhynchus mykiss). Gen Comp Endocrinol 144:224–231. doi:10.1016/j.ygcen.2005.06.004

    Article  CAS  PubMed  Google Scholar 

  • Navarro-Martín L, Viñas J, Ribas L, Díaz N, Gutiérrez A, Di Croce L, Piferrer F (2011) DNA methylation of the gonadal aromatase (cyp19a) promoter is involved in temperature-dependent sex ratio shifts in the European sea bass. PLoS Genet 7:e1002447

    Article  PubMed  PubMed Central  Google Scholar 

  • Nunez BS, Applebaum SL (2006) Tissue- and sex-specific regulation of CYP19A1 expression in the Atlantic croaker (Micropogonias undulatus). Gen Comp Endocrinol 149:205–216. doi:10.1016/j.ygcen.2006.06.005

    Article  CAS  PubMed  Google Scholar 

  • Pan B, Toms D, Shen W, Li J (2015) MicroRNA-378 regulates oocyte maturation via the suppression of aromatase in porcine cumulus cells. Am J Physiol Endocrinol Metab 308:E525–E534. doi:10.1152/ajpendo.00480.2014

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Piferrer F, Blázquez M (2005) Aromatase distribution and regulation in fish. Fish Physiol Biochem 31:215–226

    Article  CAS  PubMed  Google Scholar 

  • Planas JV, Goetz FW, Swanson P (1997) Stimulation of brook trout ovarian steroidogenesis by gonadotropins I and II is mediated by the cyclic adenosine 3′, 5′-monophosphate/protein kinase A pathway. Biol Reprod 57:647–654

    Article  CAS  PubMed  Google Scholar 

  • Sampath Kumar R, Ijiri S, Trant JM (2000) Changes in the expression of genes encoding steroidogenic enzymes in the channel catfish (Ictalurus punctatus) ovary throughout a reproductive cycle. Biol Reprod 63:1676–1682

    Article  CAS  PubMed  Google Scholar 

  • Schmittgen T, Livak K (2008) Analyzing real-time PCR data by the comparative CT method. Nat Protoc 3:1101–1108

    Article  CAS  PubMed  Google Scholar 

  • Stocco C (2008) Aromatase expression in the ovary: hormonal and molecular regulation. Steroids 73:473–487

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tchoudakova A, Callard GV (1998) Identification of multiple CYP19 genes encoding different cytochrome P450 aromatase isozymes in brain and ovary. Endocrinology 139:2179–2189

    CAS  PubMed  Google Scholar 

  • Westerfield M (2000) The zebrafish book: a guide for the laboratory use of zebrafish (Danio rerio). University of Oregon Press, Eugene

    Google Scholar 

  • Xu S, Linher-Melville K, Yang BB, Wu D, Li J (2011) Micro-RNA378 (miR-378) regulates ovarian estradiol production by targeting aromatase. Endocrinology 152:3941–3951. doi:10.1210/en.2011-1147

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang Y, Zhang S, Liu Z, Zhang L, Zhang W (2013) Epigenetic modifications during sex change repress gonadotropin stimulation of Cyp19a1a in a teleost ricefield eel (Monopterus albus). Endocrinology 154:2881–2890

    Article  CAS  PubMed  Google Scholar 

  • Zhang Z, Zhu B, Ge W (2014) Genetic analysis of zebrafish gonadotropin (FSH and LH) functions by TALEN-mediated gene disruption. Mol Endocriol 29:76–98

    Article  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported in part by the Marine Science Base Project for Scientific Research Training and Capacity Enhancement—Xiamen University, the National Natural Science Foundation of China (Nos. J1210050 and 31201977), the Natural Science Foundation of Fujian Province (No. 2013J05029), and Xiamen Southern Oceanographic Center (No. 14GZY019NF19). Professor John Hodgkiss of The University of Hong Kong is thanked for his help with the English.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Shi Xi Chen.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Bai, J., Gong, W., Wang, C. et al. Dynamic methylation pattern of cyp19a1a core promoter during zebrafish ovarian folliculogenesis. Fish Physiol Biochem 42, 947–954 (2016). https://doi.org/10.1007/s10695-015-0187-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10695-015-0187-x

Keywords

Navigation