Discovery of a possible role of asprosin in ovarian follicular function

in Journal of Molecular Endocrinology
Authors:
Excel Rio S Maylem Department of Animal and Food Sciences, Oklahoma State University, Stillwater, Oklahoma, USA

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Leon J Spicer Department of Animal and Food Sciences, Oklahoma State University, Stillwater, Oklahoma, USA

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Isadora Batalha Department of Agriculture, Veterinary, and Rangeland Sciences, University of Nevada, Reno, Nevada, USA

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Luis F Schutz Department of Agriculture, Veterinary, and Rangeland Sciences, University of Nevada, Reno, Nevada, USA

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Correspondence should be addressed to L J Spicer: Leon.spicer@okstate.edu
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Asprosin is a novel fasting-induced protein encoded by fibrillin-1 (FBN1) gene, produced when FBN1 is cleaved by the enzyme furin, and is associated with insulin resistance and polycystic ovarian syndrome in humans. To characterize mRNA abundance of FBN1, FURIN, and the presumed asprosin receptor, olfactory receptor family 4 subfamily M member 1 (OR4M1) in granulosa (GC) and theca cells (TC), and identify hormones regulating FBN1 mRNA expression, GC and TC from small (1–5 mm; SM) and large (>8 mm; LG) follicles were collected from ovaries of heifers obtained at an abattoir and used for real-time PCR gene expression analysis or in vitro evaluation of hormone regulation and asprosin effects. SMTC had 151-fold greater (P < 0.05) FBN1 mRNA abundance than SMGC, and LGTC had 50-fold greater FBN1 mRNA than LGGC. In contrast, OR4M1 mRNA was 81-fold greater in SMGC than LGGC and did not differ from SMTC, but LGTC had 9-fold greater OR4M1 mRNA than LGGC. FURIN mRNA was 2.6-fold greater in SMTC than SMGC, but did not differ among follicular sizes. In cultured TC, leptin, insulin, LH, IGF1 and steroids did not affect FBN1 mRNA, but TGFB1 increased (P < 0.05) FBN1 mRNA by 2.2-fold; EGF and FGFs increased FBN1 mRNA by 1.3- to 1.5-fold. Asprosin enhanced LH-induced TC androstenedione production, reduced IGF1-induced TC proliferation, and had no effect on progesterone production. Developmental regulation of FBN1, FURIN and OR4M1 along with direct effects of asprosin on TC suggests that asprosin may be a novel regulator of ovarian follicular function.

 

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  • Alan M, Gurlek B, Yilmaz A, Aksit M, Aslanipour B, Gulhan I, Mehmet C & Taner CE 2019 Asprosin: a novel peptide hormone related to insulin resistance in women with polycystic ovary syndrome. Gynecological Endocrinology 35 220223. (https://doi.org/10.1080/09513590.2018.1512967)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Bastian NA, Bayne RA, Hummitzsch K, Hatzirodos N, Bonner WM, Hartanti MD, Irving-Rodgers HF, Anderson RA & Rodgers RJ 2016 Regulation of fibrillins and modulators of TGFβ in fetal bovine and human ovaries. Reproduction 152 127137. (https://doi.org/10.1530/REP-16-0172)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Dentis JL, Schreiber NB, Gilliam JN, Schutz LF & Spicer LJ 2017 Changes in brain ribonuclease (BRB) mRNA in granulosa cells (GC) of dominant versus subordinate ovarian follicles of cattle and the regulation of BRB gene expression in bovine GC. Domestic Animal Endocrinology 55 3240. (https://doi.org/10.1016/j.domaniend.2015.10.008)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Duerrschmid C, He Y, Wang C, Li C, Bournat JC, Romere C, Saha PK, Lee ME, Phillips KJ & Jain M et al. 2017 Asprosin is a centrally acting orexigenic hormone. Nature Medicine 23 1444–1453. (https://doi.org/10.1038/nm.4432)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Hatzirodos N, Bayne RA, Irving-Rodgers HF, Hummitzsch K, Sabatier L, Lee S, Bonner W, Gibson MA, Rainey WE & Carr BR et al. 2011 Linkage of regulators of TGF-β activity in the fetal ovary to polycystic ovary syndrome. FASEB Journal 25 22562265. (https://doi.org/10.1096/fj.11-181099)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Hatzirodos N, Hummitzsch K, Irving-Rodgers HF, Breen J, Perry VEA, Anderson RA & Rodgers RJ 2019 Transcript abundance of stromal and thecal cell related genes during bovine ovarian development. PLoS ONE 14 e0213575. (https://doi.org/10.1371/journal.pone.0213575)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Hoffmann JG, Xie W & Chopra AR 2020 Energy regulation mechanism and therapeutic potential of asprosin. Diabetes 69 559566. (https://doi.org/10.2337/dbi19-0009)

  • Hsueh AJW, Kawamura K, Cheng Y & Fause BCJM 2015 Intraovarian control of early folliculogenesis. Endocrine Reviews 36 124. (https://doi.org/10.1210/er.2014-1020)

  • Jones ASK & Shikanov A 2019 Follicle development as an orchestrated signaling network in a 3D organoid. Journal of Biological Engineering 13 2. (https://doi.org/10.1186/s13036-018-0134-3)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Kissin EY, Lemaire R, Korn JH & Lafyatis R 2002 Transforming growth factor beta induces fibroblast fibrillin-1 matrix formation. Arthritis and Rheumatism 46 30003009. (https://doi.org/10.1002/art.10621)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Langhout DJ, Spicer LJ & Geisert RD 1991 Development of a culture system for bovine granulosa cells: effects of growth hormone, estradiol, and gonadotropins on cell proliferation, steroidogenesis, and protein synthesis. Journal of Animal Science 69 33213334. (https://doi.org/10.2527/1991.6983321x)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Lemaire R, Farina G, Bayle J, Dimarzio M, Pendergrass SA, Milano A, Perbal B, Whitfield ML & Lafyatis R 2010 Antagonistic effect of the matricellular signaling protein CCN3 on TGF-beta- and Wnt-mediated fibrillinogenesis in systemic sclerosis and Marfan syndrome. Journal of Investigative Dermatology 130 15141523. (https://doi.org/10.1038/jid.2010.15)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Li X, Liao M, Shen R, Zhang LK, Hu H, Wu J, Wang X, Qu H, Guo S & Long M et al. 2018 Plasma asprosin levels are associated with glucose metabolism, lipid and sex hormone profiles in females with metabolic-related diseases. Mediators of Inflammation 2018 7375294. (https://doi.org/10.1155/2018/7375294)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Li E, Shan H, Chen L, Long A, Zhang Y, Liu Y, Jia L, Wei F, Han J & Li T et al. 2019 OLFR734 mediates glucose metabolism as a receptor of asprosin. Cell Metabolism 30 319 .e8328.e8. (https://doi.org/10.1016/j.cmet.2019.05.022)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Liu YX, Zhang Y, Li YY, Liu XM, Wang XX, Zhang CL, Hao CF & Deng SL 2019 Regulation of follicular development and differentiation by intra-ovarian factors and endocrine hormones. Frontiers in Bioscience 24 983993.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Meng TG, Hu MW, Ma XS, Huang L, Liang QX, Yuan Y, Hou Y, Wang H, Schatten H & Wang ZB et al. 2017 Oocyte-specific deletion of furin leads to female infertility by causing early secondary follicle arrest in mice. Cell Death and Disease 8 e2846. (https://doi.org/10.1038/cddis.2017.231)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Monget P & Monniaux D 1995 Growth factors and the control of folliculogenesis. Journal of Reproduction and Fertility. Supplement 49 321333. (https://doi.org/10.1530/biosciprocs.3.025)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Morrell BC, Perego MC, Maylem ERS, Zhang L, Schütz LF & Spicer LJ 2020 Regulation of the transcription factor E2F1 mRNA in ovarian granulosa cells of cattle. Journal of Animal Science 98 18. (https://doi.org/10.1093/jas/skz376)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Nilsson EE, Doraiswamy V & Skinner MK 2003 Transforming growth factor-beta isoform expression during bovine ovarian antral follicle development. Molecular Reproduction and Development 66 237246. (https://doi.org/10.1002/mrd.10350)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Palma GA, Argañaraz ME, Barrera AD, Rodler D, Mutto & Sinowatz F 2012 Biology and biotechnology of follicle development. Thescientificworldjournal 2012 938138. (https://doi.org/10.1100/2012/938138)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Pizzo F, Caloni F, Schutz LF, Totty ML & Spicer LJ 2015 Individual and combined effects of deoxynivalenol and α-zearalenol on cell proliferation and steroidogenesis of granulosa cells in cattle. Environmental Toxicology and Pharmacology 40 722728. (https://doi.org/10.1016/j.etap.2015.08.025)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Pizzo F, Caloni F, Schreiber NB, Cortinovis C & Spicer LJ 2016 In vitro effects of deoxynivalenol and zearalenone major metabolites alone and combined, on cell proliferation, steroid production and gene expression in bovine small-follicle granulosa cells. Toxicon 109 7083. (https://doi.org/10.1016/j.toxicon.2015.11.018)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Prodoehl MJ, Irving-Rodgers HF, Bonner WM, Sullivan TM, Micke GC, Gibson MA, Perry VE & Rodgers RJ 2009 Fibrillins and latent TGFβ binding proteins in bovine ovaries of offspring following high or low protein diets during pregnancy of dams. Molecular and Cellular Endocrinology 307 133141. (https://doi.org/10.1016/j.mce.2009.03.002)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Richards JS, Ren YA, Candelaria N, Adams JE & Rajkovic A 2018 Ovarian follicular theca cell recruitment, differentiation, and impact on fertility: 2017 update. Endocrine Reviews 39 120. (https://doi.org/10.1210/er.2017-00164)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Robker RL & Richards JS 1998 Hormonal control of the cell cycle in ovarian cells: proliferation versus differentiation. Biology of Reproduction 59 476482. (https://doi.org/10.1095/biolreprod59.3.476)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Rodgers RJ, Irving-Rodgers HF & Russell DL 2003 Extracellular matrix of the developing ovarian follicle. Reproduction 126 415424. (https://doi.org/10.1530/rep.0.1260415)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Romere C, Duerrschmid C, Bournat J, Constable P, Jain M, Xia F, Saha PK, Del Solar M, Zhu B & York B et al. 2016 Asprosin, a fasting-induced glucogenic protein hormone. Cell 165 566579. (https://doi.org/10.1016/j.cell.2016.02.063)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Rosenfield RL & Ehrmann DA 2016 The pathogenesis of polycystic ovary syndrome (PCOS): the hypothesis of PCOS as functional ovarian hyperandrogenism revisited. Endocrine Reviews 37 467520. (https://doi.org/10.1210/er.2015-1104)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Schmittgen TD & Zakrajsek BA 2000 Effect of experimental treatment on housekeeping gene expression: validation by real-time, quantitative RT-PCR. Journal of Biochemical and Biophysical Methods 46 6981. (https://doi.org/10.1016/s0165-022x(0000129-9)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Schreiber NB & Spicer LJ 2012 Effects of fibroblast growth factor 9 (FGF9) on steroidogenesis and gene expression and control of FGF9 mRNA in bovine granulosa cells. Endocrinology 153 44914501. (https://doi.org/10.1210/en.2012-1003)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Schreiber NB, Totty ML & Spicer LJ 2012 Expression and effect of fibroblast growth factor 9 in bovine theca cells. Journal of Endocrinology 215 167175. (https://doi.org/10.1530/JOE-12-0293)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Schütz LF, Schreiber NB, Gilliam JN, Cortinovis C, Totty ML, Caloni F, Evans JR & Spicer LJ 2016 Changes in fibroblast growth factor 9 mRNA in granulosa and theca cells during ovarian follicular growth in dairy cattle. Journal of Dairy Science 99 91439151. (https://doi.org/10.3168/jds.2015-10667)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Sekar N, Garmey JC & Veldhuis JD 2000 Mechanisms underlying the steroidogenic synergy of insulin and luteinizing hormone in porcine granulosa cells: joint amplification of pivotal sterol-regulatory genes encoding the low-density lipoprotein (LDL) receptor, steroidogenic acute regulatory (stAR) protein and cytochrome P450 side-chain cleavage (P450scc) enzyme. Molecular and Cellular Endocrinology 159 2535. (https://doi.org/10.1016/s0303-7207(9900203-8)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Sengle G & Sakai LY 2015 The fibrillin microfibril scaffold: a niche for growth factors and mechanosensation? Matrix Biology 47 312. (https://doi.org/10.1016/j.matbio.2015.05.002)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Skinner MK & Coffey RJJ 1988 Regulation of ovarian cell growth through the local production of transforming growth factor-alpha by theca cells. Endocrinology 123 26322638. (https://doi.org/10.1210/endo-123-6-2632)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Spicer LJ 2005 Effects of estradiol on bovine thecal cell function in vitro: dependence on insulin and gonadotropins. Journal of Dairy Science 88 24122421. (https://doi.org/10.3168/jds.S0022-0302(0572919-2)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Spicer LJ & Stewart RE 1996 Interactions among basic fibroblast growth factor, epidermal growth factor, insulin, and insulin-like growth factor-I (IGF-I) on cell numbers and steroidogenesis of bovine thecal cells: role of IGF-I receptors. Biology of Reproduction 54 255263. (https://doi.org/10.1095/biolreprod54.1.255)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Spicer LJ, Aad PY, Allen D, Mazerbourg S & Hsueh AJ 2006 Growth differentiation factor-9 has divergent effects on proliferation and steroidogenesis of bovine granulosa cells. Journal of Endocrinology 189 329339. (https://doi.org/10.1677/joe.1.06503)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Stewart RE, Spicer LJ, Hamilton TD & Keefer BE 1995 Effects of insulin-like growth factor I and insulin on proliferation and on basal and luteinizing hormone-induced steroidogenesis of bovine thecal cells: involvement of glucose and receptors for insulin-like growth factor I and luteinizing hormone. Journal of Animal Science 73 37193731. (https://doi.org/10.2527/1995.73123719x)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Tajima K, Orisaka M, Mori T & Kotsuji F 2007 Ovarian theca cells in follicular function. Reproductive Biomedicine Online 15 591609. (https://doi.org/10.1016/s1472-6483(1060392-6)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Tsuji N, Kamagata C, Furuya M, Kobayashi D, Yagihashi A, Morita T, Horita S & Watanabe N 2002 Selection of an internal control gene for quantitation of mRNA in colonic tissues. Anticancer Research 22 41734178.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Voge JL, Aad PY, Santiago CA, Goad DW, Malayer JR, Allen DT & Spicer LJ 2004 Effect of insulin-like growth factors (IGF), FSH, and leptin on IGF-binding-protein mRNA expression in bovine granulosa and theca cells: quantitative detection by real-time PCR. Peptides 25 21952203. (https://doi.org/10.1016/j.peptides.2004.07.008)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Wang Y, Qu H, Xiong X, Qiu Y, Liao Y, Chen Y, Zheng Y & Zheng H 2018 Plasma asprosin concentrations are increased in individuals with glucose dysregulation and correlated with insulin resistance and first-phase insulin secretion. Mediators of Inflammation 2018 9471583. (https://doi.org/10.1155/2018/9471583)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Wang M, Yin C, Wang L, Liu Y, Li H, Li M, Yi X & Xiao Y 2019 Serum asprosin concentrations are increased and associated with insulin resistance in children with obesity. Annals of Nutrition and Metabolism 75 205212. (https://doi.org/10.1159/000503808)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Yada H, Hosokawa K, Tajima K, Hasegawa Y & Kotsuji F 1999 Role of ovarian theca and granulosa cell interaction in hormone production and cell growth during the bovine follicular maturation process. Biology of Reproduction 61 14801486. (https://doi.org/10.1095/biolreprod61.6.1480)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Young JM & McNeilly AS 2010. Theca: the forgotten cell of the ovarian follicle. Reproduction 140 489504. (https://doi.org/10.1530/REP-10-0094)

  • Zhang L, Schütz LF, Robinson CL, Totty ML & Spicer LJ 2017 Evidence that gene expression of ovarian follicular tight junction proteins is regulated in vivo and in vitro in cattle. Journal of Animal Science 95 13131324. (https://doi.org/10.2527/jas.2016.0892)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Zilberberg L, Todorovic V, Dabovic B, Horiguchi M, Couroussé T, Sakai LY & Rifkin DB 2012 Specificity of latent TGF-β binding protein (LTBP) incorporation into matrix: role of fibrillins and fibronectin. Journal of Cellular Physiology 227 38283836. (https://doi.org/10.1002/jcp.24094)

    • PubMed
    • Search Google Scholar
    • Export Citation