The role of vaspin in porcine corpus luteum

in Journal of Endocrinology
View More View Less
  • 1 Department of Physiology and Toxicology of Reproduction, Jagiellonian University in Krakow, Krakow, Poland
  • 2 Department of Endocrinology, Jagiellonian University in Krakow, Krakow, Poland
  • 3 INRAE, UMR85, Unité Physiologie de la Reproduction et des Comportements, Nouzilly, France

Correspondence should be addressed to A Rak: agnieszka.rak@uj.edu.pl
Restricted access

Vaspin, visceral adipose tissue-derived serine protease inhibitor, plays important roles in inflammation, obesity, and glucose metabolism. Our recent research has shown the expression and role of vaspin in the function of ovarian follicles. However, whether vaspin regulates steroidogenesis and luteolysis in the corpus luteum (CL) is still unknown. The aim of this study was first to determine the expression of vaspin and its receptor GRP78 in porcine CL at the early, middle, and late stages of the luteal phase. Next, we investigated the hormonal regulation of vaspin levels in luteal cells in response to luteinizing hormone (LH), progesterone (P4), and prostaglandin PGE2 and PGF2α. Finally, we determined vaspin’s direct impact on luteal cells steroidogenesis, luteolysis and kinases phosphorylation. Our results are the first to show higher vaspin/GRP78 expression in middle and late vs early stages; immunohistochemistry showed cytoplasmic vaspin/GRP78 localization in small and large luteal cells. In vitro, we found that LH, P4, PGE2, and PGF2α significantly decreased vaspin levels. Furthermore, vaspin stimulated steroidogenesis by the activation of the GRP78 receptor and protein kinase A (PKA). Also, vaspin increased the ratio of luteotropic PGE2 to luteolytic PGF2α secretion via GRP78 and mitogen-activated kinase (MAP3/1). Moreover, vaspin, in a dose-dependent manner, decreased GRP78 expression, while it, in a time-dependent manner, increased kinases PKA and MAPK3/1 phosphorylation. Taken together, we found that vaspin/GRP78 expression depends on the luteal phase stage and vaspin affects luteal cells endocrinology, indicating that vaspin is a new regulator of luteal cells steroidogenesis and CL formation.

 

      Society for Endocrinology

Sept 2018 onwards Past Year Past 30 Days
Abstract Views 80 80 80
Full Text Views 4 4 4
PDF Downloads 3 3 3
  • Arosh JA, Banu SK, Chapdelaine P, Madore E, Sirois J & Fortier MA 2004 Prostaglandin biosynthesis, transport, and signaling in corpus luteum: a basis for autoregulation of luteal function. Endocrinology 145 25512560. (https://doi.org/10.1210/en.2003-1607)

    • Search Google Scholar
    • Export Citation
  • Bao JP, Jiang LF, Li J, Chen WP, Hu PF & Wu LD 2014 Visceral adipose tissue-derived serine protease inhibitor inhibits interleukin-1β-induced catabolic and inflammatory responses in murine chondrocytes. Molecular Medicine Reports 10 21912197. (https://doi.org/10.3892/mmr.2014.2478)

    • Search Google Scholar
    • Export Citation
  • Bruun JM, Pedersen SB, Kristensen K & Richelsen B 2002 Effects of pro-inflammatory cytokines and chemokines on leptin production in human adipose tissue in vitro. Molecular and Cellular Endocrinology 190 9199. (https://doi.org/10.1016/s0303-7207(0200007-2)

    • Search Google Scholar
    • Export Citation
  • Cheng L, Shi H, Jin Y, Li X, Pan J, Lai Y, Lin Y, Jin Y, Roy G & Zhao A et al. 2016 Adiponectin deficiency leads to female subfertility and ovarian dysfunctions in mice. Endocrinology 157 48754887. (https://doi.org/10.1210/en.2015-2080)

    • Search Google Scholar
    • Export Citation
  • Dawid M, Mlyczynska E, Kurowska P, Sierpowski M & Rak A 2019 Apelin decreased placental hormone secretion by human trophoblast BeWo cells via apelin receptor, protein kinase A and extracellular signal-regulated kinases 1/2 activation. Journal of Physiology and Pharmacology 70 95907. (https://doi.org/10.26402/jpp.2019.6.08)

    • Search Google Scholar
    • Export Citation
  • Diaz FJ, Anderson LE, Wu YL, Rabot A, Tsai SJ & Wiltbank MC 2002 Regulation of progesterone and prostaglandin F2alpha production in the CL. Molecular and Cellular Endocrinology 191 6580. (https://doi.org/10.1016/S0303-7207(0200056-4)

    • Search Google Scholar
    • Export Citation
  • Dogan K, Ekin M, Helvacioğlu Ç & Yaşar L 2017 Can serum vaspin levels predict clomiphene resistance in infertile women with PCOS? European Journal of Obstetrics, Gynecology, and Reproductive Biology 217 611. (https://doi.org/10.1016/j.ejogrb.2017.08.006)

    • Search Google Scholar
    • Export Citation
  • Galvão A, Tramontano A, Rebordão MR, Amaral A, Bravo PP, Szóstek A, Skarzynski D, Mollo A & Ferreira-Dias G 2014 Opposing roles of leptin and ghrelin in the equine corpus luteum regulation: an in vitro study. Mediators of Inflammation 2014 682193. (https://doi.org/10.1155/2014/682193)

    • Search Google Scholar
    • Export Citation
  • Gao J, Tian J, Lv Y, Shi F, Kong F, Shi H & Zhao L 2009 Leptin induces functional activation of cyclooxygenase-2 through JAK2/STAT3, MAPK/ERK, and PI3K/AKT pathways in human endometrial cancer cells. Cancer Science 100 389395. (https://doi.org/10.1111/j.1349-7006.2008.01053.x)

    • Search Google Scholar
    • Export Citation
  • González CR, Caminos JE, Vázquez MJ, Garcés MF, Cepeda LA, Angel A, González AC, García-Rendueles ME, Sangiao-Alvarellos S & López M et al. 2009 Regulation of visceral adipose tissue-derived serine protease inhibitor by nutritional status, metformin, gender and pituitary factors in rat white adipose tissue. Journal of Physiology 587 37413750. (https://doi.org/10.1113/jphysiol.2009.172510)

    • Search Google Scholar
    • Export Citation
  • Gregoraszczuk E 1983 Steroid hormone release in cultures of pig corpus luteum and granulosa cells: effect of LH, hCG, PRL and estradiol. Endocrinologia Experimentalis 17 5968.

    • Search Google Scholar
    • Export Citation
  • Gregoraszczuk EL & Michas N 1999 Progesterone and estradiol secretion by porcine luteal cells is influenced by individual and combined treatment with prostaglandins E2 and F2alpha throughout the estrus cycle. Prostaglandins and Other Lipid Mediators 57 231241. (https://doi.org/10.1016/s0090-6980(9900009-x)

    • Search Google Scholar
    • Export Citation
  • Hatsumi T & Yamamuro Y 2006 Downregulation of estrogen receptor gene expression by exogenous 17beta-estradiol in the mammary glands of lactating mice. Experimental Biology and Medicine 231 311316. (https://doi.org/10.1177/153537020623100311)

    • Search Google Scholar
    • Export Citation
  • Hegyi K, Fülöp KA, Kovács KJ, Falus A & Tóth S 2004 High leptin level is accompanied with decreased long leptin receptor transcript in histamine deficient transgenic mice. Immunology Letters 92 193197. (https://doi.org/10.1016/j.imlet.2003.11.029)

    • Search Google Scholar
    • Export Citation
  • Heiker JT 2014 Vaspin (serpinA12) in obesity, insulin resistance, and inflammation. Journal of Peptide Science 20 299306. (https://doi.org/10.1002/psc.2621)

    • Search Google Scholar
    • Export Citation
  • Hida K, Wada J, Eguchi J, Zhang H, Baba M, Seida A, Hashimoto I, Okada T, Yasuhara A & Nakatsuka A et al. 2005 Visceral adipose tissue-derived serine protease inhibitor: a unique insulin-sensitizing adipocytokine in obesity. PNAS 102 1061010615. (https://doi.org/10.1073/pnas.0504703102)

    • Search Google Scholar
    • Export Citation
  • Hierlihy AM, Cooke GM, Curran IH, Mehta R, Karamanos L & Price CA 2006 Effects of ciprofibrate on testicular and adrenal steroidogenic enzymes in the rat. Reproductive Toxicology 22 3743. (https://doi.org/10.1016/j.reprotox.2005.11.001)

    • Search Google Scholar
    • Export Citation
  • Jiang YF, Tsui KH, Wang PH, Lin CW, Wang JY, Hsu MC, Chen YC & Chiu CH 2011 Hypoxia regulates cell proliferation and steroidogenesis through protein kinase A signaling in bovine corpus luteum. Animal Reproduction Science 129 152161. (https://doi.org/10.1016/j.anireprosci.2011.12.004)

    • Search Google Scholar
    • Export Citation
  • Klöting N, Kovacs P, Kern M, Heiker JT, Fasshauer M, Schön MR, Stumvoll M, Beck-Sickinger AG & Blüher M 2011 Central vaspin administration acutely reduces food intake and has sustained blood glucose-lowering effects. Diabetologia 54 18191823. (https://doi.org/10.1007/s00125-011-2137-1)

    • Search Google Scholar
    • Export Citation
  • Kumar L, Panda RP, Hyder I, Yadav VP, Sastry KV, Sharma GT, Mahapatra RK, Bag S, Bhure SK & Das GK et al. 2012 Expression of leptin and its receptor in corpus luteum during estrous cycle in buffalo (Bubalus bubalis). Animal Reproduction Science 135 817. (https://doi.org/10.1016/j.anireprosci.2012.08.030)

    • Search Google Scholar
    • Export Citation
  • Kurowska P, Mlyczyńska E, Barbe A, Staub C, Gregoraszczuk E, Dupont J & Rak A 2019a Vaspin in the pig ovarian follicles: expression and regulation by different hormones. Reproduction 158 135146. (https://doi.org/10.1530/REP-19-0034)

    • Search Google Scholar
    • Export Citation
  • Kurowska P, Mlyczyńska E, Dawid M, Opydo-Chanek M, Dupont J & Rak A 2019b In vitro effects of vaspin on porcine granulosa cell proliferation, cell cycle progression, and apoptosis by activation of GRP78 receptor and several kinase signaling pathways including MAP3/1, AKT, and STAT3. International Journal of Molecular Sciences 20 5816. (https://doi.org/10.3390/ijms20225816)

    • Search Google Scholar
    • Export Citation
  • Kurowska P, Mlyczyńska E, Dawid M, Dupont J & Rak A 2020 Role of vaspin in porcine ovary: effect on signaling pathways and steroid synthesis via GRP78 receptor and protein kinase A. Biology of Reproduction 102 12901305. (https://doi.org/10.1093/biolre/ioaa027)

    • Search Google Scholar
    • Export Citation
  • Kurzynska A, Chojnowska K, Bogacki M & Bogacka I 2016 PPAR ligand association with prostaglandin F2α and E2 synthesis in the pig corpus luteum-an in vitro study. Animal Reproduction Science 172 157163. (https://doi.org/10.1016/j.anireprosci.2016.07.014)

    • Search Google Scholar
    • Export Citation
  • Lai X, Zhang C, Wang J, Wang C, Lan X, Zhang C, Lei C & Chen H 2013 mRNA expression pattern and association study with growth traits of bovine vaspin gene. Molecular Biology Reports 40 44994505. (https://doi.org/10.1007/s11033-013-2542-2)

    • Search Google Scholar
    • Export Citation
  • Lappas M, Permezel M & Rice GE 2005 Leptin and adiponectin stimulate the release of proinflammatory cytokines and prostaglandins from human placenta and maternal adipose tissue via nuclear factor-kappaB, peroxisomal proliferator-activated receptor-gamma and extracellularly regulated kinase 1/2. Endocrinology 146 33343342. (https://doi.org/10.1210/en.2005-0406)

    • Search Google Scholar
    • Export Citation
  • Li Q, Chen R, Moriya J, Yamakawa J, Sumino H, Kanda T & Takahashi T 2008 A novel adipocytokine, visceral adipose tissue-derived serine protease inhibitor (vaspin), and obesity. Journal of International Medical Research 36 625629. (https://doi.org/10.1177/147323000803600402)

    • Search Google Scholar
    • Export Citation
  • Maleszka A, Smolinska N, Nitkiewicz A, Kiezun M, Chojnowska K, Dobrzyn K, Szwaczek H & Kaminski T 2014 Adiponectin expression in the porcine ovary during the oestrous cycle and its effect on ovarian steroidogenesis. International Journal of Endocrinology 2014 957076. (https://doi.org/10.1155/2014/957076)

    • Search Google Scholar
    • Export Citation
  • Mesen TB & Young SL 2015 Progesterone and the luteal phase: a requisite to reproduction. Obstetrics and Gynecology Clinics of North America 42 135151. (https://doi.org/10.1016/j.ogc.2014.10.003)

    • Search Google Scholar
    • Export Citation
  • Mierzyński R, Poniedziałek-Czajkowska E, Dłuski D, Patro-Małysza J, Kimber-Trojnar Ż, Majsterek M & Leszczyńska-Gorzelak B 2019 Nesfatin-1 and vaspin as potential novel biomarkers for the prediction and early diagnosis of gestational diabetes mellitus. International Journal of Molecular Sciences 20 159. (https://doi.org/10.3390/ijms20010159)

    • Search Google Scholar
    • Export Citation
  • Nakatsuka A, Wada J, Iseda I, Teshigawara S, Higashio K, Murakami K, Kanzaki M, Inoue K, Terami T & Katayama A et al. 2013 Visceral adipose tissue-derived serine proteinase inhibitor inhibits apoptosis of endothelial cells as a ligand for the cell-surface GRP78/voltage-dependent anion channel complex. Circulation Research 112 771780. (https://doi.org/10.1161/CIRCRESAHA.111.300049)

    • Search Google Scholar
    • Export Citation
  • Park HJ, Park JY, Kim JW, Yang SG, Jung JM, Kim MJ, Park JJ & Koo DB 2017 Regulation of the endoplasmic reticulum stress by BIP/GRP78 is involved in meiotic maturation of porcine oocytes in vitro. Development and Reproduction 21 407415. (https://doi.org/10.12717/DR.2017.21.4.407)

    • Search Google Scholar
    • Export Citation
  • Przygrodzka E, Kaczmarek MM, Kaczynski P & Ziecik AJ 2016 Steroid hormones, prostanoids, and angiogenic systems during rescue of the corpus luteum in pigs. Reproduction 151 135147. (https://doi.org/10.1530/REP-15-0332)

    • Search Google Scholar
    • Export Citation
  • Rak A, Drwal E, Wróbel A & Gregoraszczuk 2015 Resistin is a survival factor for porcine ovarian follicular cells. Reproduction 150 343355. (https://doi.org/10.1530/REP-15-0255)

    • Search Google Scholar
    • Export Citation
  • Rak A, Drwal E, Rame C, Knapczyk-Stwora K, Słomczyńska M, Dupont J & Gregoraszczuk EL 2017 Expression of apelin and apelin receptor (APJ) in porcine ovarian follicles and in vitro effect of apelin on steroidogenesis and proliferation through APJ activation and different signaling pathways. Theriogenology 96 126135. (https://doi.org/10.1016/j.theriogenology.2017.04.014)

    • Search Google Scholar
    • Export Citation
  • Reverchon M, Bertoldo MJ, Ramé C, Froment P & Dupont J 2014 Chemerin (RARRES2) decreases in vitro granulosa cell steroidogenesis and blocks oocyte meiotic progression in bovine species. Biology of Reproduction 90 102. (https://doi.org/10.1095/biolreprod.113.117044)

    • Search Google Scholar
    • Export Citation
  • Różycka M, Kurowska P, Grzesiak M, Kotula-Balak M, Tworzydło W, Rame C, Gregoraszczuk E, Dupont J & Rak A 2018 Apelin and apelin receptor at different stages of corpus luteum development and effect of apelin on progesterone secretion and 3β-hydroxysteroid dehydrogenase (3β-HSD) in pigs. Animal Reproduction Science 192 251260. (https://doi.org/10.1016/j.anireprosci.2018.03.021)

    • Search Google Scholar
    • Export Citation
  • Rytelewska E, Kisielewska K, Kiezun M, Dobrzyn K, Gudelska M, Rak A, Dupont J, Kaminska B, Kaminski T & Smolinska N 2020 Expression of chemerin and its receptors in the ovaries of prepubertal and mature gilts. Molecular Reproduction and Development 87 739762. (https://doi.org/10.1002/mrd.23391)

    • Search Google Scholar
    • Export Citation
  • Shirasuna K, Shimizu T, Sayama K, Asahi T, Sasaki M, Berisha B, Schams D & Miyamoto A 2008 Expression and localization of apelin and its receptor APJ in the bovine corpus luteum during the estrous cycle and prostaglandin F2alpha-induced luteolysis. Reproduction 135 519525. (https://doi.org/10.1530/REP-07-0409)

    • Search Google Scholar
    • Export Citation
  • Siawrys G & Smolinska N 2013 In vitro effects of luteinizing hormone, progesterone and oestradiol-17β on leptin gene expression and leptin secretion by porcine luteal cells obtained in early pregnancy. Journal of Physiology and Pharmacology 64 513520.

    • Search Google Scholar
    • Export Citation
  • Sirotkin AV, Rafay J & Kotwica J 2009 Leptin controls rabbit ovarian function in vivo and in vitro: possible interrelationships with ghrelin. Theriogenology 72 765772. (https://doi.org/10.1016/j.theriogenology.2009.05.011)

    • Search Google Scholar
    • Export Citation
  • Stocco C, Telleria C & Gibori G 2007 The molecular control of corpus luteum formation, function, and regression. Endocrine Reviews 28 117149. (https://doi.org/10.1210/er.2006-0022)

    • Search Google Scholar
    • Export Citation
  • Stouffer R & Hennebold J 2015 Structure, function, and regulation of the corpus luteum. In Knobil and Neill’s Physiology of Reproduction, 4th ed., pp. 10231076. Eds Plant T, Zeleznik A. Amsterdam, Netherlands: Elsevier Inc.

    • Search Google Scholar
    • Export Citation
  • Tan BK, Heutling D, Chen J, Farhatullah S, Adya R, Keay SD, Kennedy CR, Lehnert H & Randeva HS 2008 Metformin decreases the adipokine vaspin in overweight women with polycystic ovary syndrome concomitant with improvement in insulin sensitivity and a decrease in insulin resistance. Diabetes 57 15011507. (https://doi.org/10.2337/db08-0127)

    • Search Google Scholar
    • Export Citation
  • Vandesompele J, De Preter K, Pattyn F, Poppe B, Van Roy N, De Paepe A & Speleman F 2002 Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes. Genome Biology 3 RESEARCH0034. (https://doi.org/10.1186/gb-2002-3-7-research0034)

    • Search Google Scholar
    • Export Citation
  • von Loeffelholz C, Möhlig M, Arafat AM, Isken F, Spranger J, Mai K, Randeva HS, Pfeiffer AF & Weickert MO 2010 Circulating vaspin is unrelated to insulin sensitivity in a cohort of nondiabetic humans. European Journal of Endocrinology 162 507513. (https://doi.org/10.1530/EJE-09-0737)

    • Search Google Scholar
    • Export Citation
  • Waclawik A 2011 Novel insights into the mechanisms of pregnancy establishment: regulation of prostaglandin synthesis and signaling in the pig. Reproduction 142 389399. (https://doi.org/10.1530/REP-11-0033)

    • Search Google Scholar
    • Export Citation
  • Ziecik AJ, Przygrodzka E, Jalali BM & Kaczmarek MM 2018 Regulation of the porcine corpus luteum during pregnancy. Reproduction 156 R57R67. (https://doi.org/10.1530/REP-17-0662)

    • Search Google Scholar
    • Export Citation