Apoptotic germ cells regulate Sertoli cell lipid storage and fatty acid oxidation

in Reproduction
Authors:
Mariana Regueira Centro de Investigaciones Endocrinológicas ‘Dr César Bergadá’ CONICET-FEI-División de Endocrinología Hospital de Niños Ricardo Gutiérrez, Buenos Aires, Argentina

Search for other papers by Mariana Regueira in
Current site
Google Scholar
PubMed
Close
,
Agostina Gorga Centro de Investigaciones Endocrinológicas ‘Dr César Bergadá’ CONICET-FEI-División de Endocrinología Hospital de Niños Ricardo Gutiérrez, Buenos Aires, Argentina

Search for other papers by Agostina Gorga in
Current site
Google Scholar
PubMed
Close
,
Gustavo Marcelo Rindone Centro de Investigaciones Endocrinológicas ‘Dr César Bergadá’ CONICET-FEI-División de Endocrinología Hospital de Niños Ricardo Gutiérrez, Buenos Aires, Argentina

Search for other papers by Gustavo Marcelo Rindone in
Current site
Google Scholar
PubMed
Close
,
Eliana Herminia Pellizzari Centro de Investigaciones Endocrinológicas ‘Dr César Bergadá’ CONICET-FEI-División de Endocrinología Hospital de Niños Ricardo Gutiérrez, Buenos Aires, Argentina

Search for other papers by Eliana Herminia Pellizzari in
Current site
Google Scholar
PubMed
Close
,
Selva Beatriz Cigorraga Centro de Investigaciones Endocrinológicas ‘Dr César Bergadá’ CONICET-FEI-División de Endocrinología Hospital de Niños Ricardo Gutiérrez, Buenos Aires, Argentina

Search for other papers by Selva Beatriz Cigorraga in
Current site
Google Scholar
PubMed
Close
,
María Noel Galardo Centro de Investigaciones Endocrinológicas ‘Dr César Bergadá’ CONICET-FEI-División de Endocrinología Hospital de Niños Ricardo Gutiérrez, Buenos Aires, Argentina

Search for other papers by María Noel Galardo in
Current site
Google Scholar
PubMed
Close
,
María Fernanda Riera Centro de Investigaciones Endocrinológicas ‘Dr César Bergadá’ CONICET-FEI-División de Endocrinología Hospital de Niños Ricardo Gutiérrez, Buenos Aires, Argentina

Search for other papers by María Fernanda Riera in
Current site
Google Scholar
PubMed
Close
, and
Silvina Beatriz Meroni Centro de Investigaciones Endocrinológicas ‘Dr César Bergadá’ CONICET-FEI-División de Endocrinología Hospital de Niños Ricardo Gutiérrez, Buenos Aires, Argentina

Search for other papers by Silvina Beatriz Meroni in
Current site
Google Scholar
PubMed
Close

Correspondence should be addressed to S B Meroni; Email: smeroni@cedie.org.ar
Restricted access
Rent on DeepDyve

Sign up for journal news

The presence of lipid droplets (LD) and the utilization of fatty acids (FA) as a source of energy are Sertoli cell (SC) putative characteristics. It is well known that SCs can phagocyte and degrade apoptotic germ cells (AGC) resulting in increasing lipid content and ATP levels. A relationship between the regulation of lipid storage and of lipid oxidation in SC might be envisaged. The aim of this study was to analyze whether AGC and FA are able to simultaneously regulate molecular mechanisms involved in lipid storage and in FA oxidation in SC. The experimental model utilized in this study consisted in SC cultures obtained from 20-day-old rats that were co-cultured with AGC or treated with palmitic acid (PA, 500 μM) for 24 and 48 h. AGC and PA increase LD, triacylglycerol (TAG) content and mRNA levels of Plin1, Plin2, Plin3 (proteins involved in TAG storage). Simultaneously, AGC and PA rise the extent of FA oxidation and mRNA levels of Cpt1 and Lcad (proteins involved in FA degradation). Results also show that peroxisome proliferator-activated receptor (PPAR) transcriptional activity, transcription factor which participate in lipid metabolism regulation, increases by AGC and PA treatment in SC. Additionally, the presence of a PPARg antagonist decreases the upregulation of LD content and Plin1 expression. Similarly, the presence of a PPARb/d antagonist reduces the increase in FA oxidation and Cpt1 mRNA levels. Altogether these results suggest that AGC and FA, which probably generate PPAR ligands, regulate lipid storage and fatty acid utilization, contributing to the energy homeostasis in the seminiferous tubules.

 

  • Collapse
  • Expand
  • Abreu I & David-Ferreira JF 1982 Fine structure of seminiferous tubules from prenatally irradiated rats. Cell and Tissue Research 222 143152.

  • Arimura N, Horiba T, Imagawa M, Shimizu M & Sato R 2004 The peroxisome proliferator-activated receptor gamma regulates expression of the perilipin gene in adipocytes. Journal of Biological Chemistry 279 1007010076. (https://doi.org/10.1074/jbc.M308522200)

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • Bensinger SJ & Tontonoz P 2008 Integration of metabolism and inflammation by lipid-activated nuclear receptors. Nature 454 470477. (https://doi.org/10.1038/nature07202)

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • Bensoussan K, Morales C & Hermo L 1998 Vitamin E deficiency causes incomplete spermatogenesis and affects the structural differentiation of epithelial cells of the epididymis in the rat. Journal of Andrology 19 266288. (https://doi.org/10.1002/j.1939-4640.1998.tb02006.x)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Bickel PE, Tanseyc JT & Welte MA 2009 PAT proteins, an ancient family of lipid droplet proteins that regulate cellular lipid stores. Biochimica et Biophysica Acta 1791 419440. (https://doi.org/10.1016/j.bbalip.2009.04.002)

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • Brasaemle DL 2007 Thematic review series: adipocyte biology. The perilipin family of structural lipid droplet proteins: stabilization of lipid droplets and control of lipolysis. Journal of Lipid Research 48 25472559. (https://doi.org/10.1194/jlr.R700014-JLR200)

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • Chawla A, Schwarz EJ, Dimaculangan DD & Lazar MA 1994 Peroxisome proliferator-activated receptor (PPAR) gamma: adipose-predominant expression and induction early in adipocyte differentiation. Endocrinology 135 798800. (https://doi.org/10.1210/endo.135.2.8033830)

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • Fan B, Ikuyama S, Gu JQ, Wei P, Oyama J, Inoguchi T & Nishimura J 2009 Oleic acid-induced ADRP expression requires both AP-1 and PPAR response elements, and is reduced by Pycnogenol through mRNA degradation in NMuLi liver cells. American Journal of Physiology: Endocrinology and Metabolism 297 E112E123. (https://doi.org/10.1152/ajpendo.00119.2009)

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • Furland NE, Luquez JM, Oresti OM & Aveldaño MI 2011 Mild testicular hyperthermia transiently increases lipid droplet accumulation and modifies sphingolipid and glycerophospholipid acyl chains in the rat testis. Lipids 46 443454. (https://doi.org/10.1007/s11745-011-3527-3)

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • Galardo MN, Regueira M, Riera MF, Pellizzari EH, Cigorraga SB & Meroni SB 2014 Lactate regulates rat male germ cell function through reactive oxygen species. PLoS ONE 9 e88024. (https://doi.org/10.1371/journal.pone.0088024)

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • Gillot I, Jehl-Pietri C, Gounon P, Luquet S, Rassoulzadegan M, Grimaldi P & Vidal F 2005 Germ cells and fatty acids induce translocation of CD36 scavenger receptor to the plasma membrane of Sertoli cells. Journal of Cell Science 118 30273035. (https://doi.org/10.1242/jcs.02430)

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • Glatz JF 2015 Lipids and lipid binding proteins: a perfect match. Prostaglandins, Leukotrienes and Essential Fatty Acids 93 4549. (https://doi.org/10.1016/j.plefa.2014.07.011)

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • Gorga A, Rindone GM, Regueira M, Pellizzari EH, Camberos MC, Cigorraga SB, Riera MF, Galardo MN & Meroni SB 2017 PPARg activation regulates lipid droplet formation and lactate production in rat Sertoli cells. Cell and Tissue Research 369 611624. (https://doi.org/10.1007/s00441-017-2615-y)

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • Green S & Wahli W 1994 Peroxisome proliferator-activated receptors: finding the orphan a home. Molecular and Cellular Endocrinology 100 149153. (https://doi.org/10.1016/0303-7207(94)90294-1)

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • Haemmerle G, Moustafa T, Woelkart G, Büttner S, Schmidt A, van de Weijer T, Hesselink M, Jaeger D, Kienesberger PC & Zierler K et al.2011 ATGL-mediated fat catabolism regulates cardiac mitochondrial function via PPAR-a and PGC-1. Nature Medicine 17 10761085. (https://doi.org/10.1038/nm.2439)

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • Haj-Yasein NN, Berg O, Jernerén F, Refsum H, Nebb HI & Dalen KT 2017 Cysteine deprivation prevents induction of peroxisome proliferator-activated receptor gamma-2 and adipose differentiation of 3T3-L1 cells. Biochimica et Biophysica Acta 1862 623635. (https://doi.org/10.1016/j.bbalip.2017.02.009)

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • Huckins C 1978 The morphology and kinetics of spermatogonial degeneration in normal adult rats: an analysis using a simplified classification of the germinal epithelium. Anatomical Record 90 905926. (https://doi.org/10.1002/ar.1091900410)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Hurtado de Catalfo GE & Gómez Dumm IN 2005 Influence of testosterone on polyunsaturated fatty acid biosynthesis in Sertoli cells in culture. Cell Biochemistry and Function 23 175180. (https://doi.org/10.1002/cbf.1135)

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • Issemann I & Green S 1990 Activation of a member of the steroid hormone receptor superfamily by peroxisome proliferators. Nature 347 645650. (https://doi.org/10.1038/347645a0)

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • Jutte NH, Jansen R, Grootegoed JA, Rommerts FF, Clausen OP & van der Molen HJ 1982 Regulation of survival of rat pachytene spermatocytes by lactate supply from Sertoli cells. Journal of Reproduction and Fertility 65 431438. (https://doi.org/10.1530/jrf.0.0650431)

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • Jutte NH, Eikvar L, Levy FO & Hansson V 1985 Metabolism of palmitate in cultured rat Sertoli cells. Journal of Reproduction and Fertility 73 497503. (https://doi.org/10.1530/jrf.0.0730497)

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • Kerr JB & de Kretser DM 1974 Proceedings: the role of the Sertoli cell in phagocytosis of the residual bodies of spermatids. Journal of Reproduction and Fertility 36 439440. (https://doi.org/10.1530/jrf.0.0360439)

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • Kerr JB, Mayberry RA & Irby DC 1984 Morphometric studies on lipid inclusions in Sertoli cell during the spermatogenic cicle in the rat. Cell and Tissue Research 236 699709

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Krey G, Braissant O, L’Horset F, Kalkhoven E, Perroud M, Parker MG & Wahli W 1997 Fatty acids, eicosanoids, and hypolipidemic agents identified as ligands of peroxisome proliferator-activated receptors by coactivator-dependent receptor ligand assay. Molecular Endocrinology 11 779791. (https://doi.org/10.1210/mend.11.6.0007)

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • Labarca C & Paigen K 1980 A simple, rapid, and sensitive DNA assay procedure. Analytical Biochemistry 102 344352. (https://doi.org/10.1016/0003-2697(80)90165-7)

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • Liu M, Qi L, Zeng Y, Yang Y, Bi Y, Shi X, Zhu H, Zhou Z & Sha J 2012 Transient scrotal hyperthermia induces lipid droplet accumulation and reveals a different ADFP expression pattern between the testes and liver in mice. PLoS ONE 7 e45694 (https://doi.org/10.1371/journal.pone.0045694)

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • Liu K, Liu P, Liu R & Wu X 2015 Dual AO/EB staining to detect apoptosis in osteosarcoma cells compared with flow cytometry. Medical Science Monitor Basic Research 21 1520. (https://doi.org/10.12659/MSMBR.895463)

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • Meroni SB, Riera MF, Pellizzari EH & Cigorraga SB 2002 Regulation of rat Sertoli cell function by FSH: possible role of phosphatidylinositol 3-kinase/protein kinase B pathway. Journal of Endocrinology 174 195204. (https://doi.org/10.1677/joe.0.1740195)

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • Michalik L, Auwerx J, Berger JP, Chatterjee VK, Glass CK, Gonzalez FJ, Grimaldi PA, Kadowaki T, Lazar MA & O’Rahilly S et al.2006 International Union of Pharmacology. LXI. Peroxisome proliferator-activated receptors. Pharmacological Reviews 58 726741. (https://doi.org/10.1124/pr.58.4.5)

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • Mottillo EP, Bloch AE, Leff T & Granneman JG. 2012 Lipolytic products activate peroxisome proliferator-activated receptor (PPAR) a and d in brown adipocytes to match fatty acid oxidation with supply. Journal of Biological Chemistry 287 2503825048. (https://doi.org/10.1074/jbc.M112.374041)

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • Oresti GM, García-López J, Aveldaño MI & Del Mazo J 2013 Cell-type-specific regulation of genes involved in testicular lipid metabolism: fatty acid-binding proteins, diacylglycerol acyltransferases, and perilipin 2. Reproduction 146 471480. (https://doi.org/10.1530/REP-13-0199)

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • Pineau C, Le Magueresse B, Courtens JL & Jégou B 1991 Study in vitro of the phagocytic function of Sertoli cells in the rat. Cell and Tissue Research 264 589598. (https://doi.org/10.1007/BF00319048)

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • Rasmussen BB & Wolfe RR 1999 Regulation of fatty acid oxidation in skeletal muscle. Annual Review of Nutrition 19 463484. (https://doi.org/10.1146/annurev.nutr.19.1.463)

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • Regueira M, Riera MF, Galardo MN, Pellizzari EH, Cigorraga SB & Meroni SB 2014 Activation of PPAR a and PPAR b/d regulates Sertoli cell metabolism. Molecular and Cellular Endocrinology 382 271281. (https://doi.org/10.1016/j.mce.2013.10.006)

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • Regueira M, Riera MF, Galardo MN, Camberos MC, Pellizzari EH, Cigorraga SB & Meroni SB 2015 FSH and bFGF regulate the expression of genes involved in Sertoli cell energetic metabolism. General and Comparative Endocrinology 222 124133 (https://doi.org/10.1016/j.ygcen.2015.08.011)

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • Riera MF, Meroni SB, Schteingart HF, Pellizzari EH & Cigorraga SB 2002 Regulation of lactate production and glucose transport as well as glucose transport 1 and lactate dehydrogenase A mRNA levels by basic fibroblast growth factor in rat Sertoli cell. Journal of Endocrinology 173 335343 (https://doi.org/10.1677/joe.0.1730335)

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • Riera MF, Galardo MN, Pellizzari EH, Meroni SB & Cigorraga SB 2009 Molecular mechanisms involved in Sertoli cell adaptation to glucose deprivation. American Journal of Physiology: Endocrinology and Metabolism 297 E907E914. (https://doi.org/10.1152/ajpendo.00235.2009)

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • Tang T, Abbott MJ, Ahmadian M, Lopes AB, Wang Y & Sul HS 2013 Desnutrin/ATGL activates PPARd to promote mitochondrial function for insulin secretion in islet b cells. Cell Metabolism 18 883895. (https://doi.org/10.1016/j.cmet.2013.10.012)

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • Thach TT, Lee CK, Park HW, Lee SJ & Lee SJ 2016 Syringaresinol induces mitochondrial biogenesis through activation of PPARb pathway in skeletal muscle cells. Bioorganic and Medicinal Chemistry Letters 26 39783983. (https://doi.org/10.1016/j.bmcl.2016.07.001)

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • Ueno H & Mori H 1990 Morphometrical analysis of Sertoli cell ultrastructure during the seminiferous epitelial cycle in rats. Biology of Reproduction 43 769776. (https://doi.org/10.1095/biolreprod43.5.769)

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • Wang YX, Lee CH, Tiep S, Yu RT, Ham J, Kang H & Evans RM 2003 Peroxisome-proliferator-activated receptor delta activates fat metabolism to prevent obesity. Cell 113 159170. (https://doi.org/10.1016/S0092-8674(03)00269-1)

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • Wang H, Wang H, Xiong W, Chen Y, Ma Q, Ma J, Ge Y & Han D 2006 Evaluation on the phagocytosis of apoptotic spermatogenic cells by Sertoli cells in vitro through detecting lipid droplet formation by Oil Red O staining. Reproduction 132 485492. (https://doi.org/10.1530/rep.1.01213)

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • Xie P, Zhang AT, Wang C, Azzam MM & Zou XT 2012 Molecular cloning, characterization, and expression analysis of fatty acid translocase (FAT/CD36) in the pigeon (Columba livia domestica). Poultry Science 91 16701679. (https://doi.org/10.3382/ps.2011-02097)

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • Xiong W, Wang H, Wu H, Chen Y & Han D 2009 Apoptotic spermatogenic cells can be energy sources for Sertoli cells. Reproduction 137 469479. (https://doi.org/10.1530/REP-08-0343)

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation