FGF2/FGFR signaling promotes cumulus–oocyte complex maturation in vitro

in Reproduction
Authors:
Chao Du Key Lab of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education, Wuhan, China
College of Animal Science and Technology of Huazhong Agricultural University, Wuhan, China

Search for other papers by Chao Du in
Current site
Google Scholar
PubMed
Close
,
John S Davis Olson Center for Women’s Health, Department of Obstetrics and Gynecology, University of Nebraska Medical Center, Omaha, Nebraska, USA
Omaha Veterans Affairs Medical Center, Omaha, Nebraska, USA

Search for other papers by John S Davis in
Current site
Google Scholar
PubMed
Close
,
Chao Chen Key Lab of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education, Wuhan, China
College of Animal Science and Technology of Huazhong Agricultural University, Wuhan, China

Search for other papers by Chao Chen in
Current site
Google Scholar
PubMed
Close
,
Zan Li Key Lab of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education, Wuhan, China
College of Animal Science and Technology of Huazhong Agricultural University, Wuhan, China

Search for other papers by Zan Li in
Current site
Google Scholar
PubMed
Close
,
Ye Cao Key Lab of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education, Wuhan, China
College of Animal Science and Technology of Huazhong Agricultural University, Wuhan, China

Search for other papers by Ye Cao in
Current site
Google Scholar
PubMed
Close
,
Hui Sun Key Lab of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education, Wuhan, China
College of Animal Science and Technology of Huazhong Agricultural University, Wuhan, China

Search for other papers by Hui Sun in
Current site
Google Scholar
PubMed
Close
,
Bao-Shun Shao Key Lab of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education, Wuhan, China
College of Animal Science and Technology of Huazhong Agricultural University, Wuhan, China

Search for other papers by Bao-Shun Shao in
Current site
Google Scholar
PubMed
Close
,
Yu-Xin Lin Key Lab of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education, Wuhan, China
College of Animal Science and Technology of Huazhong Agricultural University, Wuhan, China

Search for other papers by Yu-Xin Lin in
Current site
Google Scholar
PubMed
Close
,
Yong-Sheng Wang Key Lab of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education, Wuhan, China
College of Animal Science and Technology of Huazhong Agricultural University, Wuhan, China

Search for other papers by Yong-Sheng Wang in
Current site
Google Scholar
PubMed
Close
,
Li-Guo Yang Key Lab of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education, Wuhan, China
College of Animal Science and Technology of Huazhong Agricultural University, Wuhan, China

Search for other papers by Li-Guo Yang in
Current site
Google Scholar
PubMed
Close
, and
Guo-Hua Hua Key Lab of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education, Wuhan, China
College of Animal Science and Technology of Huazhong Agricultural University, Wuhan, China

Search for other papers by Guo-Hua Hua in
Current site
Google Scholar
PubMed
Close

Correspondence should be addressed to G-H Hua; Email: huaguohua09@gmail.com
Restricted access
Rent on DeepDyve

Sign up for journal news

Fibroblast growth factor 2 (FGF2), a member of FGF family, binds with FGF receptors (FGFR) to initiate biological functions in various somatic cells. However, little is known regarding the role of FGF2/FGFR on oocyte meiosis. In this study, we investigated expression patterns and functions of FGF2/FGFR during in vitro maturation (IVM) of mouse cumulus-oocyte complexes (COCs). Among four FGFRs, Ffgr1 was the most abundant in COCs. The transcripts for Fgf2 and Ffgr1 in COCs increased during IVM. Ffgr1 was present in oocytes and cumulus cells, while Fgf2 was present in only cumulus cells. Treatment of COCs with the selective FGFR inhibitor SU5402 blocked oocyte meiotic progression and downregulated expression of Bmp15 and Gdf9. In contrast, supplement of FGF2 promoted oocyte meiotic progression and upregulated Bmp15 and Gdf9 expression. Inhibition of FGFR with SU5402 reduced cumulus expansion and expressions of Ptx3, Has2 and Tnfaip6. Treatment with FGF2 increased Ptx3 and Has2 expression. Inhibition of FGFR had no effect on meiotic progression of denuded oocytes (DOs). However, co-culture of DOs with COCs or supplementation with FGF2 promoted meiotic progression of DOs. Inhibition of FGF2/FGFR signaling also downregulated Ffgr1 expression, while supplemental FGF2 upregulated Fgfr1 expression. Furthermore, inhibition of FGFR in COCs interrupted the c-Mos/MAPK pathway and maturation-promoting factor (MPF), as indicated by downregulation of oocyte c-mos and Ccnb1 transcripts, respectively. Overall, this study suggests that FGF2 produced by cumulus cells, activates a FGF2/FGFR autocrine/paracrine loop within COCs to regulate cumulus expansion and oocyte meiosis. These findings reveal a novel role for FGF2/FGFR signaling during in vitro maturation of COCs.

 

  • Collapse
  • Expand
  • Abouzaripour M, Fathi F, Daneshi E, Mortezaee K, Rezaie MJ & Abdi M 2018 Combined effect of retinoic acid and basic fibroblast growth factor on maturation of mouse oocyte and subsequent fertilization and development. International Journal of Fertility and Sterility 12 6871. (https://doi.org/10.22074/ijfs.2018.5293)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Acuna-Hernández DG, Arreola-Mendoza L, Santacruz-Márquez R, García-Zepeda SP, Parra-Forero LY, Olivares-Reyes JA & Hernández-Ochoa I 2018 Bisphenol A alters oocyte maturation by prematurely closing gap junctions in the cumulus cell-oocyte complex. Toxicology and Applied Pharmacology 344 1322. (https://doi.org/10.1016/j.taap.2018.02.011)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Almeida AP, Saraiva MV, Alves Filho JG, Silva GM, Gonçalves RF, Brito IR, Silva AW, Lima AK, Cunha RM & Silva JR et al. 2012 Gene expression and immunolocalization of fibroblast growth factor 2 in the ovary and its effect on the in vitro culture of caprine preantral ovarian follicles. Reproduction in Domestic Animals 47 2025. (https://doi.org/10.1111/j.1439-0531.2011.01793.x)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Barros RG, Lima PF, Soares ACS, Sanches L, Price CA & Buratini J 2019 Fibroblast growth factor 2 regulates cumulus differentiation under the control of the oocyte. Journal of Assisted Reproduction and Genetics 36 905913. (https://doi.org/10.1007/s10815-019-01436-7)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Belli M & Shimasaki S 2018 Molecular aspects and clinical relevance of gdf9 and bmp15 in ovarian function. Vitamins and Hormones 107 317348. (https://doi.org/10.1016/bs.vh.2017.12.003)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Buratini J & Caixeta ES 2012 Paracrine and autocrine factors in the differentiation of the cumulus-oocyte complex. Animal Reproduction 9 414419.

  • Downs SM 1989 Specificity of epidermal growth factor action on maturation of the murine oocyte and cumulus oophorus in vitro. Biology of Reproduction 41 371379. (https://doi.org/10.1095/biolreprod41.2.371)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Emori C, Wigglesworth K, Fujii W, Naito K, Eppig JJ & Sugiura K 2013 Cooperative effects of 17β-estradiol and oocyte-derived paracrine factors on the transcriptome of mouse cumulus cells. Endocrinology 154 48594872. (https://doi.org/10.1210/en.2013-1536)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Fields SD, Hansen PJ & Ealy AD 2011 Fibroblast growth factor requirements for in vitro development of bovine embryos. Theriogenology 75 14661475. (https://doi.org/10.1016/j.theriogenology.2010.12.007)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Furukawa S, Matsuno Y, Emori C, Fujii W, Naito K & Sugiura K 2014 Expression and regulation of FGF receptors in mouse granulosa cells. Journal of Mammalian Ova Research 31 8692. (https://doi.org/10.1274/jmor.31.86)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Gao Y, Ren J, Zhang L, Zhang Y, Wu X, Jiang H, Xu F, Yuan B, Yu X & Zhang J 2014 The effects of demecolcine, alone or in combination with sucrose on bovine oocyteprotrusion rate, MAPK1 protein level and c-mos gene expression level. Cellular Physiology and Biochemistry 34 19741982. (https://doi.org/10.1159/000366393)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Gode F, Gulekli B, Dogan E, Korhan P, Dogan S, Bige O, Cimrin D & Atabey N 2011 Influence of follicular fluid GDF9 and BMP15 on embryo quality. Fertility and Sterility 95 22742278. (https://doi.org/10.1016/j.fertnstert.2011.03.045)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • He B, Lin J, Li J, Mi Y, Zeng W & Zhang C 2012 Basic fibroblast growth factor suppresses meiosis and promotes mitosis of ovarian germ cells in embryonic chickens. General and Comparative Endocrinology 176 173181. (https://doi.org/10.1016/j.ygcen.2012.01.012)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Hua G, Lv X, He C, Remmenga SW, Rodabough KJ, Dong J, Yang L, Lele SM, Yang P & Zhou J et al. 2016 YAP induces high-grade serous carcinoma in Fallopian tube secretory epithelial cells. Oncogene 35 22472265. (https://doi.org/10.1038/onc.2015.288)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Kawashima I, Liu Z, Mullany LK, Mihara T, Richards JS & Shimada M 2012 EGF-like factors induce expansion of the cumulus cell-oocyte complexes by activating calpain-mediated cell movement. Endocrinology 153 39493959. (https://doi.org/10.1210/en.2012-1059)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Kubiak JZ 2013 Protein kinase assays for measuring MPF and MAPK activities in mouse and rat oocytes and early embryos. Methods in Molecular Biology 957 7789. (https://doi.org/10.1007/978-1-62703-191-2_5)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Lin J, Jia Y, Zeng W, Mi Y & Zhang C 2012 Basic FGF promotes proliferation of ovarian granulosa cells in the laying chickens via FGFR1 and PKC pathway. Reproduction in Domestic Animals 47 135142. (https://doi.org/10.1111/j.1439-0531.2011.01813.x)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Liu XM, Yan MQ, Ji SY, Sha QQ, Huang T, Zhao H, Liu HB, Fan HY & Chen ZJ 2018 Loss of oocyte Rps26 in mice arrests oocyte growth and causes premature ovarian failure. Cell Death and Disease 9 1144. (https://doi.org/10.1038/s41419-018-1196-3)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Lu J, Zhang W, Lin C, Xie M, Wang J, Wang Z & Wang S 2010 Expression and distribution of fibroblast growth factor receptor 1, 2 and 3 in Kunming mouse oocyte and preimplantation embryos. Chinese Journal of Anatomy 33 296298, 332. (https://doi.org/10.3969/j.issn.1001-1633.2010.03.005)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Lu CL, Yan J, Zhi X, Xia X, Wang TR, Yan LY, Yu Y, Ding T, Gao JM & Li R et al. 2015 Basic fibroblast growth factor promotes macaque follicle development in vitro. Reproduction 149 425433. (https://doi.org/10.1530/REP-14-0557)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Matsuno Y, Onuma A, Fujioka YA, Yasuhara K, Fujii W, Naito K & Sugiura K 2017 Effects of exosome-like vesicles on cumulus expansion in pigs in vitro. Journal of Reproduction and Development 63 5158. (https://doi.org/10.1262/jrd.2016-124)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Mondal S, Mor A, Reddy IJ, Nandi S & Parameswaragupta P 2015 Effect of fibroblast growth factor 2 (FGF2) and insulin transferrin selenium (ITS) on in vitro maturation, fertilization and embryo development in sheep. Brazilian Archives of Biology and Technology 58 521525. (https://doi.org/10.1590/S1516-8913201500059)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Mor A, Mondal S, Reddy IJ, Nandi S & Gupta P 2018 Molecular cloning and expression of FGF2 gene in pre-implantation developmental stages of in vitro-produced sheep embryos. Reproduction in Domestic Animals 53 895903. (https://doi.org/10.1111/rda.13182)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Ornitz DM & Itoh N 2015 The fibroblast growth factor signaling pathway. Wiley Interdisciplinary Reviews: Developmental Biology 4 215266. (https://doi.org/10.1002/wdev.176)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Pereira LMC, Bersano PRO, Rocha DD & Lopes MD 2019 Effect of EGF on expression and localization of maturation‐promoting factor, mitogen‐activated protein kinase, p34cdc2 and cyclin B during different culture periods on in vitro maturation of canine oocytes. Reproduction in Domestic Animals 54 325341. (https://doi.org/10.1111/rda.13365)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Price CA 2016 Mechanisms of fibroblast growth factor signaling in the ovarian follicle. Journal of Endocrinology 228 R31R 43. (https://doi.org/10.1530/JOE-15-0414)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Rong Y, Ji SY, Zhu YZ, Wu YW, Shen L & Fan HY 2019 ZAR1 and ZAR2 are required for oocyte meiotic maturation by regulating the maternal transcriptome and mRNA translational activation. Nucleic Acids Research 47 1138711402. (https://doi.org/10.1093/nar/gkz863)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Santos JM, Menezes VG, Barberino RS, Macedo TJ, Lins TL, Gouveia BB, Barros VR, Santos LP, Gonçalves RJ & Matos MH 2014 Immunohistochemical localization of fibroblast growth factor-2 in the sheep ovary and its effects on pre-antral follicle apoptosis and development in vitro. Reproduction in Domestic Animals 49 522528. (https://doi.org/10.1111/rda.12322)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Shimada M, Umehara T & Hoshino Y 2016 Roles of epidermal growth factor (EGF)-like factor in the ovulation process. Reproductive Medicine and Biology 15 201216. (https://doi.org/10.1007/s12522-016-0236-x)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Soto-Heras S, Catalá MG, Roura M, Menéndez-Blanco I, Piras AR, Izquierdo D & Paramio MT 2019 Effects of melatonin on oocyte developmental competence and the role of melatonin receptor 1 in juvenile goats. Reproduction in Domestic Animals 54 381390. (https://doi.org/10.1111/rda.13378)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Sugimura S, Ritter LJ, Rose RD, Thompson JG, Smitz J, Mottershead DG & Gilchrist RB 2015 Promotion of EGF receptor signaling improves the quality of low developmental competence oocytes. Developmental Biology 403 139149. (https://doi.org/10.1016/j.ydbio.2015.05.008)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Sugiura K, Su YQ, Diaz FJ, Pangas SA, Sharma S, Wigglesworth K, O'Brien MJ, Matzuk MM, Shimasaki S & Eppig JJ 2007 Oocyte-derived BMP15 and FGFs cooperate to promote glycolysis in cumulus cells. Development 134 25932603. (https://doi.org/10.1242/dev.006882)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Sugiura K, Su YQ, Li Q, Wigglesworth K, Matzuk MM & Eppig JJ 2009 Fibroblast growth factors and epidermal growth factor cooperate with oocyte-derived members of the TGFbeta superfamily to regulate Spry2 mRNA levels in mouse cumulus cells. Biology of Reproduction 81 833841. (https://doi.org/10.1095/biolreprod.109.078485)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Tian X, Wang F, Zhang L, He C, Ji P, Wang J, Zhang Z, Lv D, Abulizi W & Wang X et al. 2017 Beneficial effects of melatonin on the in vitro maturation of sheep oocytes and its relation to melatonin receptors. International Journal of Molecular Sciences 18 834. (https://doi.org/10.3390/ijms18040834)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • von Otte S, Paletta JR, Becker S, König S, Fobker M, Greb RR, Kiesel L, Assmann G, Diedrich K & Nofer JR 2006 Follicular fluid high density lipoprotein-associated sphingosine 1-phosphate is a novel mediator of ovarian angiogenesis. Journal of Biological Chemistry 281 53985405. (https://doi.org/10.1074/jbc.M508759200)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Yang CR, Lowther KM, Lalioti MD & Seli E 2016 Embryonic poly(A)-binding protein (EPAB) is required for granulosa cell EGF signaling and cumulus expansion in female mice. Endocrinology 157 405416. (https://doi.org/10.1210/en.2015-1135)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Yuan Y, Spate LD, Redel BK, Tian Y, Zhou J, Prather RS & Roberts RM 2017 Quadrupling efficiency in production of genetically modified pigs through improved oocyte maturation. PNAS 114 E5796E5804. (https://doi.org/10.1073/pnas.1703998114)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Zhang K & Ealy AD 2012a Supplementing fibroblast growth factor 2 during bovine oocyte in vitro maturation promotes subsequent embryonic development. Open Journal of Animal Sciences 2 119126. (https://doi.org/10.4236/ojas.2012.22017)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Zhang K & Ealy AD 2012b Disruption of fibroblast growth factor receptor signaling in bovine cumulus-oocyte complexes during in vitro maturation reduces subsequent embryonic development. Domestic Animal Endocrinology 42 230238. (https://doi.org/10.1016/j.domaniend.2011.12.006)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Zhang K, Hansen PJ & Ealy AD 2010 Fibroblast growth factor 10 enhances bovine oocyte maturation and developmental competence in vitro. Reproduction 140 815826. (https://doi.org/10.1530/REP-10-0190)

    • PubMed
    • Search Google Scholar
    • Export Citation