An integrative view on sex differences in brain tumors

Cellular and Molecular Life Sciences

Volumn 72, Issue 17, 2015, Pages 3323-3342

  Sun, Tao ^a   Plutynski, Anya ^b,c   Ward, Stacey ^a   Rubin, Joshua B ^a  

^a WASHINGTON UNIVERSITY   (United States)

^b WASHINGTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

^c NONE   (United States)

Author keywords

Cancer; Evolution; Immunity; Metabolism; Sex determination; Sexual dimorphism

Indexed keywords

CYCLIC AMP; CYCLIN DEPENDENT KINASE INHIBITOR 2A; CYPROTERONE ACETATE; EPIDERMAL GROWTH FACTOR RECEPTOR; ESTRADIOL; ESTROGEN; ESTROGEN RECEPTOR; GAMMA INTERFERON; ISOCITRATE DEHYDROGENASE; MICRORNA; NEUROFIBROMIN; PHOSPHATIDYLINOSITOL 3,4,5 TRISPHOSPHATE 3 PHOSPHATASE; PLATELET DERIVED GROWTH FACTOR RECEPTOR; PROGESTERONE; PROTEIN MDM2; PROTEIN P53; SONIC HEDGEHOG PROTEIN; TRANSCRIPTION FACTOR SP1; WNT PROTEIN; RETINOBLASTOMA PROTEIN;

ACUTE LYMPHOBLASTIC LEUKEMIA; ADAPTIVE IMMUNITY; ANGIOGENESIS; ASTROCYTE; BLOOD BRAIN BARRIER; BRAIN METASTASIS; BRAIN TUMOR; CANCER INCIDENCE; CANCER RISK; CANCER SCREENING; CARCINOGENESIS; CARDIOVASCULAR DISEASE; CARDIOVASCULAR FUNCTION; CD4+ T LYMPHOCYTE; CDKN2A GENE; CHROMOSOME 17P; CHROMOSOME 17Q; COPY NUMBER VARIATION; EGFR GENE; ENVIRONMENTAL EXPOSURE; EPENDYMA CELL; EPENDYMOMA; EPIGENETICS; EPITHELIAL MESENCHYMAL TRANSITION; EVENT FREE SURVIVAL; GENE DELETION; GENE EXPRESSION; GENE MUTATION; GENETIC PREDISPOSITION; GENOTYPE; GLIOBLASTOMA; GLIOMA; HUMAN; IDH GENE; LYMPHOCYTE FUNCTION; MACROPHAGE; MAMMARY GLAND FAT; MEDULLOBLASTOMA; MENINGIOMA; MICROCHIMERISM; MICROGLIA; MONOCYTE; MULTIPLE SCLEROSIS; NATURAL KILLER CELL; NIDATION; NONHUMAN; OLIGODENDROGLIA; OUTCOME ASSESSMENT; OVERALL SURVIVAL; OXIDATIVE STRESS; PDGFRA GENE; PHENOTYPE; PLEIOTROPY; PREGNANCY; PREIMPLANTATION EMBRYO; PREVALENCE; PROMOTER REGION; PROSTATE CANCER; PROTEIN DEPLETION; PROTEIN FUNCTION; PUBERTY; RADIATION EXPOSURE; RB1 GENE; REVIEW; RHEUMATOID ARTHRITIS; SEX DETERMINATION; SEX DIFFERENCE; SEXUAL SELECTION; SIGNAL TRANSDUCTION; SINGLE NUCLEOTIDE POLYMORPHISM; STROMA; SYSTEMIC LUPUS ERYTHEMATOSUS; TH1 CELL; TP53 GENE; TREATMENT RESPONSE; TUMOR GROWTH; TUMOR MICROENVIRONMENT; TUMOR REGRESSION; BRAIN NEOPLASMS; EVOLUTION; FEMALE; GENE EXPRESSION REGULATION; INCIDENCE; MALE; METABOLISM; PATHOPHYSIOLOGY; PHYSIOLOGY; SEXUAL DEVELOPMENT; TREATMENT OUTCOME;

BIOLOGICAL EVOLUTION; BRAIN NEOPLASMS; CYCLIC AMP; FEMALE; GENE EXPRESSION REGULATION, DEVELOPMENTAL; GENE EXPRESSION REGULATION, NEOPLASTIC; HUMANS; INCIDENCE; MALE; RETINOBLASTOMA PROTEIN; SEX CHARACTERISTICS; TREATMENT OUTCOME; TUMOR SUPPRESSOR PROTEIN P53;

EID: 84938975105     PISSN: 1420682X     EISSN: 14209071     Source Type: Journal    
DOI: 10.1007/s00018-015-1930-2     Document Type: Review

References (214)

1. Ashley DJ (1969) A male-female differential in tumour incidence. Br J Cancer 23:21-25
2. Cook MB, McGlynn KA, Devesa SS, Freedman ND, Anderson WF (2011) Sex disparities in cancer mortality and survival. Cancer Epidemiol Biomark Prevent a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 20: 1629-1637
3. Devarahally SR, Severson RK, Chuba P, Thomas R, Bhambhani K, Hamre MR (2003) Second malignant neoplasms after primary central nervous system malignancies of childhood and adolescence. Pediatr Hematol Oncol 20:617-625
4. Eden OB, Harrison G, Richards S, Lilleyman JS, Bailey CC, Chessells JM et al (2000) Long-term follow-up of the United Kingdom Medical Research Council protocols for childhood acute lymphoblastic leukaemia, 1980-1997. Medical Research Council Childhood Leukaemia Working Party. Leukemia 14:2307-2320
5. Molife R, Lorigan P, MacNeil S (2001) Gender and survival in malignant tumours. Cancer Treat Rev 27:201-209
6. Pearce MS, Parker L (2001) Childhood cancer registrations in the developing world: still more boys than girls. Int J Cancer J Int du Cancer 91:402-406
7. Siegel R, DeSantis C, Virgo K, Stein K, Mariotto A, Smith T et al (2012) Cancer treatment and survivorship statistics, 2012. CA Cancer J Clin 62:220-241
8. Siegel R, Naishadham D, Jemal A (2012) Cancer statistics, 2012. CA Cancer J Clin 62:10-29
9. Curran EK, Sainani KL, Le GM, Propp JM, Fisher PG (2009) Gender affects survival for medulloblastoma only in older children and adults: a study from the Surveillance Epidemiology and End Results Registry. Pediatr Blood Cancer 52:60-64
10. Weil MD, Lamborn K, Edwards MS, Wara WM (1998) Influence of a child's sex on medulloblastoma outcome. JAMA 279:1474-1476
11. Sun T, Warrington NM, Rubin JB (2012) Why does Jack, and not Jill, break his crown? Sex disparity in brain tumors. Biol Sex Differ 3:3
12. Phillips HS, Kharbanda S, Chen R, Forrest WF, Soriano RH, Wu TD et al (2006) Molecular subclasses of high-grade glioma predict prognosis, delineate a pattern of disease progression, and resemble stages in neurogenesis. Cancer Cell 9:157-173
13. Verhaak RG, Hoadley KA, Purdom E, Wang V, Qi Y, Wilkerson MD et al (2010) Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1. Cancer Cell 17:98-110
14. Sun T, Warrington NM, Luo J, Brooks MD, Dahiya S, Snyder SC et al. (2014) Sexually dimorphic RB inactivation underlies mesenchymal glioblastoma prevalence in males. J Clin Invest
15. SEER Cancer Statistics Review, 1975-2011 [Internet]. National Cancer Institute. 2013. Available from: http://seer.cancer.gov/csr/1975-2011/
16. Ober C, Loisel DA, Gilad Y (2008) Sex-specific genetic architecture of human disease. Nat Rev Genet 9:911-922
17. Cho YJ, Tsherniak A, Tamayo P, Santagata S, Ligon A, Greulich H et al (2011) Integrative genomic analysis of medulloblastoma identifies a molecular subgroup that drives poor clinical outcome. J Clin Oncol 29:1424-1430
18. Kool M, Korshunov A, Remke M, Jones DT, Schlanstein M, Northcott PA et al (2012) Molecular subgroups of medulloblastoma: an international meta-analysis of transcriptome, genetic aberrations, and clinical data of WNT, SHH, Group 3, and Group 4 medulloblastomas. Acta Neuropathol 123:473-484
19. Northcott PA, Korshunov A, Witt H, Hielscher T, Eberhart CG, Mack S et al (2010) Medulloblastoma comprises four distinct molecular variants. J Clin Oncol 29:1408-1414
20. Taylor MD, Northcott PA, Korshunov A, Remke M, Cho YJ, Clifford SC et al (2012) Molecular subgroups of medulloblastoma: the current consensus. Acta Neuropathol 123:465-472
21. Gibson P, Tong Y, Robinson G, Thompson MC, Currle DS, Eden C et al (2010) Subtypes of medulloblastoma have distinct developmental origins. Nature 468:1095-1099
22. Pei Y, Moore CE, Wang J, Tewari AK, Eroshkin A, Cho YJ et al (2012) An animal model of MYC-driven medulloblastoma. Cancer Cell 21:155-167
23. Rao G, Pedone CA, Coffin CM, Holland EC, Fults DW (2003) c-Myc enhances sonic hedgehog-induced medulloblastoma formation from nestin-expressing neural progenitors in mice. Neoplasia 5:198-204
24. Read TA, Fogarty MP, Markant SL, McLendon RE, Wei Z, Ellison DW et al (2009) Identification of CD15 as a marker for tumor-propagating cells in a mouse model of medulloblastoma. Cancer Cell 15:135-147
25. Schuller U, Heine VM, Mao J, Kho AT, Dillon AK, Han YG et al (2008) Acquisition of granule neuron precursor identity is a critical determinant of progenitor cell competence to form Shh-induced medulloblastoma. Cancer Cell 14:123-134
26. Hooper CM, Hawes SM, Kees UR, Gottardo NG, Dallas PB (2014) Gene expression analyses of the spatio-temporal relationships of human medulloblastoma subgroups during early human neurogenesis. PLoS One 9:e112909
27. Batora NV, Sturm D, Jones DT, Kool M, Pfister SM, Northcott PA (2014) Transitioning from genotypes to epigenotypes: why the time has come for medulloblastoma epigenomics. Neuroscience 264:171-185
28. Witt H, Mack SC, Ryzhova M, Bender S, Sill M, Isserlin R et al (2011) Delineation of two clinically and molecularly distinct subgroups of posterior fossa ependymoma. Cancer Cell 20:143-157
29. Mack SC, Witt H, Piro RM, Gu L, Zuyderduyn S, Stutz AM et al (2014) Epigenomic alterations define lethal CIMP-positive ependymomas of infancy. Nature 506:445-450
30. Johnson RA, Wright KD, Poppleton H, Mohankumar KM, Finkelstein D, Pounds SB et al (2010) Cross-species genomics matches driver mutations and cell compartments to model ependymoma. Nature 466:632-636
31. Taylor MD, Poppleton H, Fuller C, Su X, Liu Y, Jensen P et al (2005) Radial glia cells are candidate stem cells of ependymoma. Cancer Cell 8:323-335
32. Bender S, Tang Y, Lindroth AM, Hovestadt V, Jones DT, Kool M et al (2013) Reduced H3K27me3 and DNA hypomethylation are major drivers of gene expression in K27M mutant pediatric high-grade gliomas. Cancer Cell 24:660-672
33. Buczkowicz P, Hoeman C, Rakopoulos P, Pajovic S, Letourneau L, Dzamba M et al (2014) Genomic analysis of diffuse intrinsic pontine gliomas identifies three molecular subgroups and recurrent activating ACVR1 mutations. Nat Genet 46:451-456
34. Chan KM, Fang D, Gan H, Hashizume R, Yu C, Schroeder M et al (2013) The histone H3.3K27M mutation in pediatric glioma reprograms H3K27 methylation and gene expression. Genes Dev 27:985-990
35. Fontebasso AM, Liu XY, Sturm D, Jabado N (2013) Chromatin remodeling defects in pediatric and young adult glioblastoma: a tale of a variant histone 3 tail. Brain Pathol 23:210-216
36. Khuong-Quang DA, Buczkowicz P, Rakopoulos P, Liu XY, Fontebasso AM, Bouffet E et al (2012) K27 M mutation in histone H3.3 defines clinically and biologically distinct subgroups of pediatric diffuse intrinsic pontine gliomas. Acta Neuropathol 124:439-447
37. Schwartzentruber J, Korshunov A, Liu XY, Jones DT, Pfaff E, Jacob K et al (2012) Driver mutations in histone H3.3 and chromatin remodelling genes in paediatric glioblastoma. Nature 482:226-231
38. Venneti S, Garimella MT, Sullivan LM, Martinez D, Huse JT, Heguy A et al (2013) Evaluation of histone 3 lysine 27 trimethylation (H3K27me3) and enhancer of Zest 2 (EZH2) in pediatric glial and glioneuronal tumors shows decreased H3K27me3 in H3F3A K27M mutant glioblastomas. Brain Pathol 23:558-564
39. Wu G, Broniscer A, McEachron TA, Lu C, Paugh BS, Becksfort J et al (2012) Somatic histone H3 alterations in pediatric diffuse intrinsic pontine gliomas and non-brainstem glioblastomas. Nat Genet 44:251-253
40. Parker M, Mohankumar KM, Punchihewa C, Weinlich R, Dalton JD, Li Y et al (2014) C11orf95-RELA fusions drive oncogenic NF-kappaB signalling in ependymoma. Nature 506:451-455
41. Warrington NM, Sun T, Luo J, McKinstry RC, Parkin PC, Ganzhorn S et al (2015) The cyclic AMP pathway is a sex-specific modifier of glioma risk in type I neurofibromatosis patients. Cancer Res 75:16-21
42. Norden AD, Wen PY, Kesari S (2005) Brain metastases. Curr Opin Neurol 18:654-661
43. Smedby KE, Brandt L, Backlund ML, Blomqvist P (2009) Brain metastases admissions in Sweden between 1987 and 2006. Br J Cancer 101:1919-1924
44. Tabouret E, Chinot O, Metellus P, Tallet A, Viens P, Goncalves A (2012) Recent trends in epidemiology of brain metastases: an overview. Anticancer Res 32:4655-4662
45. Nayak L, Lee EQ, Wen PY (2012) Epidemiology of brain metastases. Curr Oncol Reports 14:48-54
46. Hamilton A, Sibson NR (2013) Role of the systemic immune system in brain metastasis. Mol Cell Neurosci 53:42-51
47. Soltermann A, Tischler V, Arbogast S, Braun J, Probst-Hensch N, Weder W et al (2008) Prognostic significance of epithelial-mesenchymal and mesenchymal-epithelial transition protein expression in non-small cell lung cancer. Clin Cancer Res 14:7430-7437
48. Mikheev AM, Mikheeva SA, Trister AD, Tokita MJ, Emerson SN, Parada CA et al (2014) Periostin is a novel therapeutic target that predicts and regulates glioma malignancy. Neuro Oncol 17:372-382
49. Cruz-Orengo L, Daniels BP, Dorsey D, Basak SA, Grajales-Reyes JG, McCandless EE et al (2014) Enhanced sphingosine-1-phosphate receptor 2 expression underlies female CNS autoimmunity susceptibility. J Clin Invest 124:2571-2584
50. Marosi C, Hassler M, Roessler K, Reni M, Sant M, Mazza E et al (2008) Meningioma. Critical Rev Oncol/hematol 67:153-171
51. Guevara P, Escobar-Arriaga E, Saavedra-Perez D, Martinez-Rumayor A, Flores-Estrada D, Rembao D et al (2010) Angiogenesis and expression of estrogen and progesterone receptors as predictive factors for recurrence of meningioma. J Neurooncol 98:379-384
52. Cea-Soriano L, Wallander MA, Garcia Rodriguez LA (2012) Epidemiology of meningioma in the United Kingdom. Neuroepidemiology 39:27-34
53. Blitshteyn S, Crook JE, Jaeckle KA (2008) Is there an association between meningioma and hormone replacement therapy? J Clin Oncol 26:279-282
54. Lusis EA, Scheithauer BW, Yachnis AT, Fischer BR, Chicoine MR, Paulus W et al (2012) Meningiomas in pregnancy: a clinicopathologic study of 17 cases. Neurosurgery 71:951-961
55. Cardenas-Goicoechea SJ, Debbs RH (2011) Meningioma during pregnancy: a case report. J Reprod Med 56:81-84
56. DeGrood RM, Beemer WH, Fenner DE, Compton AA (1987) A large meningioma presenting as a neurologic emergency in late pregnancy. Obstet Gynecol 69:439-440
57. Patel S, Sharan V (2010) Meningioma in pregnancy. J Obstet Gynaecol J Inst Obstet Gynaecol 30:56-57
58. Saitoh Y, Oku Y, Izumoto S, Go J (1989) Rapid growth of a meningioma during pregnancy: relationship with estrogen and progesterone receptors-case report. Neurol Med Chir 29:440-443
59. Custer B, Longstreth WT Jr, Phillips LE, Koepsell TD, Van Belle G (2006) Hormonal exposures and the risk of intracranial meningioma in women: a population-based case-control study. BMC Cancer 6:152
60. Korhonen K, Raitanen J, Isola J, Haapasalo H, Salminen T, Auvinen A (2010) Exogenous sex hormone use and risk of meningioma: a population-based case-control study in Finland. Cancer Causes Control CCC 21:2149-2156
61. Li Q, Coulson H, Klaassen Z, Sharma S, Ramalingam P, Moses KA et al (2013) Emerging association between androgen deprivation therapy and male meningioma: significant expression of luteinizing hormone-releasing hormone receptor in male meningioma. Prostate Cancer Prostatic Dis 16:387-390
62. Cea-Soriano L, Blenk T, Wallander MA, Rodriguez LA (2012) Hormonal therapies and meningioma: is there a link? Cancer Epidemiol 36:198-205
63. Bergoglio MT, Gomez-Balaguer M, Almonacid Folch E, Hurtado Murillo F, Hernandez-Mijares A, Gomez-Balaguer M (2013) Symptomatic meningioma induced by cross-sex hormone treatment in a male-to-female transsexual. Endocrinologia y nutricion: organo de la Sociedad Espanola de. Endocrinologia y Nutricion 60:264-267
64. Deipolyi AR, Han SJ, Parsa AT (2010) Development of a symptomatic intracranial meningioma in a male-to-female transsexual after initiation of hormone therapy. J Clin Neurosci Off J Neurosurg Soc Australas 17:1324-1326
65. Gazzeri R, Galarza M, Gazzeri G (2007) Growth of a meningioma in a transsexual patient after estrogen-progestin therapy. N Engl J Med 357:2411-2412
66. Cebula H, Pham TQ, Boyer P, Froelich S (2010) Regression of meningiomas after discontinuation of cyproterone acetate in a transsexual patient. Acta Neurochir (Wien) 152:1955-1956
67. Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144:646-674
68. Donehower LA, Harvey M, Slagle BL, McArthur MJ, Montgomery CA Jr, Butel JS et al (1992) Mice deficient for p53 are developmentally normal but susceptible to spontaneous tumours. Nature 356:215-221
69. Armstrong JF, Kaufman MH, Harrison DJ, Clarke AR (1995) High-frequency developmental abnormalities in p53-deficient mice. Curr Biol CB 5:931-936
70. Chen X, Watkins R, Delot E, Reliene R, Schiestl RH, Burgoyne PS et al (2008) Sex difference in neural tube defects in p53-null mice is caused by differences in the complement of X not Y genes. Dev Neurobiol 68:265-273
71. Wang G, Fulkerson CM, Malek R, Ghassemifar S, Snyder PW, Mendrysa SM (2012) Mutations in Lyar and p53 are synergistically lethal in female mice. Birth Defects Res A 94:729-737
72. Tyner SD, Venkatachalam S, Choi J, Jones S, Ghebranious N, Igelmann H et al (2002) p53 mutant mice that display early ageing-associated phenotypes. Nature 415:45-53
73. Waskar M, Landis GN, Shen J, Curtis C, Tozer K, Abdueva D et al (2009) Drosophila melanogaster p53 has developmental stage-specific and sex-specific effects on adult life span indicative of sexual antagonistic pleiotropy. Aging 1:903-936
74. Racagni G, Pezzotta S, Giordana MT, Iuliano E, Mocchetti I, Spanu G et al (1983) Cyclic nucleotides in experimental and human brain tumors. J Neurooncol 1:61-67
75. Goldhoff P, Warrington NM, Limbrick DD Jr, Hope A, Woerner BM, Jackson E et al (2008) Targeted inhibition of cyclic AMP phosphodiesterase-4 promotes brain tumor regression. Clin Cancer Res 14:7717-7725
76. Warrington NM, Gianino SM, Jackson E, Goldhoff P, Garbow JR, Piwnica-Worms D et al (2010) Cyclic AMP supppression is sufficient to induce gliomagenesis in a mouse model of Neurofibromatosis-1. Cancer Res 70:5717-5727
77. Yang L, Jackson E, Woerner BM, Perry A, Piwnica-Worms D, Rubin JB (2007) Blocking CXCR4-mediated cyclic AMP suppression inhibits brain tumor growth in vivo. Cancer Res 67:651-658
78. He X, Zhang L, Chen Y, Remke M, Shih D, Lu F et al (2014) The G protein alpha subunit Galphas is a tumor suppressor in Sonic hedgehog-driven medulloblastoma. Nat Med 20:1035-1042
79. Bajenaru ML, Hernandez MR, Perry A, Zhu Y, Parada LF, Garbow JR et al (2003) Optic nerve glioma in mice requires astrocyte Nf1 gene inactivation and Nf1 brain heterozygosity. Cancer Res 63:8573-8577
80. Sellner J, Kraus J, Awad A, Milo R, Hemmer B, Stuve O (2011) The increasing incidence and prevalence of female multiple sclerosis-a critical analysis of potential environmental factors. Autoimmun Rev 10:495-502
81. van Vollenhoven RF (2009) Sex differences in rheumatoid arthritis: more than meets the eye. BMC Med 7:12
82. Weckerle CE, Niewold TB (2011) The unexplained female predominance of systemic lupus erythematosus: clues from genetic and cytokine studies. Clin Rev Allergy Immunol 40:42-49
83. Wang C, Dehghani B, Magrisso IJ, Rick EA, Bonhomme E, Cody DB et al (2008) GPR30 contributes to estrogen-induced thymic atrophy. Mol Endocrinol 22:636-648
84. Maret A, Coudert JD, Garidou L, Foucras G, Gourdy P, Krust A et al (2003) Estradiol enhances primary antigen-specific CD4 T cell responses and Th1 development in vivo. Essential role of estrogen receptor alpha expression in hematopoietic cells. Eur J Immunol 33:512-521
85. Gourdy P, Araujo LM, Zhu R, Garmy-Susini B, Diem S, Laurell H et al (2005) Relevance of sexual dimorphism to regulatory T cells: estradiol promotes IFN-gamma production by invariant natural killer T cells. Blood 105:2415-2420
86. Kissick HT, Sanda MG, Dunn LK, Pellegrini KL, On ST, Noel JK et al (2014) Androgens alter T-cell immunity by inhibiting T-helper 1 differentiation. Proc Natl Acad Sci USA 111:9887-9892
87. Bianchi I, Lleo A, Gershwin ME, Invernizzi P (2012) The X chromosome and immune associated genes. J Autoimmun 38:J187-J192
88. Schwarz JM, Bilbo SD (2012) Sex, glia, and development: interactions in health and disease. Horm Behav 62:243-253
89. Benarroch EE (2013) Microglia: multiple roles in surveillance, circuit shaping, and response to injury. Neurology 81:1079-1088
90. Alliot F, Godin I, Pessac B (1999) Microglia derive from progenitors, originating from the yolk sac, and which proliferate in the brain. Brain Res Dev Brain Res 117:145-152
91. Cunningham CL, Martinez-Cerdeno V, Noctor SC (2013) Microglia regulate the number of neural precursor cells in the developing cerebral cortex. J Neurosci Off J Soc Neurosci 33:4216-4233
92. Schafer DP, Lehrman EK, Kautzman AG, Koyama R, Mardinly AR, Yamasaki R et al (2012) Microglia sculpt postnatal neural circuits in an activity and complement-dependent manner. Neuron 74:691-705
93. Walton NM, Sutter BM, Laywell ED, Levkoff LH, Kearns SM, Marshall GP 2nd et al (2006) Microglia instruct subventricular zone neurogenesis. Glia 54:815-825
94. Engler JR, Robinson AE, Smirnov I, Hodgson JG, Berger MS, Gupta N et al (2012) Increased microglia/macrophage gene expression in a subset of adult and pediatric astrocytomas. PLoS One 7:e43339
95. Bettinger I, Thanos S, Paulus W (2002) Microglia promote glioma migration. Acta Neuropathol 103:351-355
96. Markovic DS, Vinnakota K, Chirasani S, Synowitz M, Raguet H, Stock K et al (2009) Gliomas induce and exploit microglial MT1-MMP expression for tumor expansion. Proc Natl Acad Sci USA 106:12530-12535
97. Ye XZ, Xu SL, Xin YH, Yu SC, Ping YF, Chen L et al (2012) Tumor-associated microglia/macrophages enhance the invasion of glioma stem-like cells via TGF-beta1 signaling pathway. J Immunol 189:444-453
98. Hussain SF, Yang D, Suki D, Aldape K, Grimm E, Heimberger AB (2006) The role of human glioma-infiltrating microglia/macrophages in mediating antitumor immune responses. Neuro Oncol 8:261-279
99. Hussain SF, Yang D, Suki D, Grimm E, Heimberger AB (2006) Innate immune functions of microglia isolated from human glioma patients. J Transl Med 4:15
100. Kees T, Lohr J, Noack J, Mora R, Gdynia G, Todt G et al (2012) Microglia isolated from patients with glioma gain antitumor activities on poly (I:C) stimulation. Neuro Oncol 14:64-78
101. Galarneau H, Villeneuve J, Gowing G, Julien JP, Vallieres L (2007) Increased glioma growth in mice depleted of macrophages. Cancer Res 67:8874-8881
102. Lenz KM, McCarthy MM (2014) A starring role for Microglia in brain sex differences. Neurosci Rev J Bring Neurobiol Neurol Psychiat
103. Lenz KM, Nugent BM, Haliyur R, McCarthy MM (2013) Microglia are essential to masculinization of brain and behavior. J Neurosci Off J Soc Neurosci 33:2761-2772
104. Schwarz JM, Sholar PW, Bilbo SD (2012) Sex differences in microglial colonization of the developing rat brain. J Neurochem 120:948-963
105. Santos-Galindo M, Acaz-Fonseca E, Bellini MJ, Garcia-Segura LM (2011) Sex differences in the inflammatory response of primary astrocytes to lipopolysaccharide. Biol Sex Differ 2:7
106. Maffini MV, Soto AM, Calabro JM, Ucci AA, Sonnenschein C (2004) The stroma as a crucial target in rat mammary gland carcinogenesis. J Cell Sci 117:1495-1502
107. Dolberg DS, Hollingsworth R, Hertle M, Bissell MJ (1985) Wounding and its role in RSV-mediated tumor formation. Science 230:676-678
108. Stewart TA, Mintz B (1981) Successive generations of mice produced from an established culture line of euploid teratocarcinoma cells. Proc Natl Acad Sci USA 78:6314-6318
109. Zuk M, Stoehr AM (2010) Sex differences in susceptibility to infection: an evolutionary perspective. Klein SRC (ed) Springer, Berlin
110. Bize P, Criscuolo F, Metcalfe NB, Nasir L, Monaghan P (2009) Telomere dynamics rather than age predict life expectancy in the wild. Proc Biol Sci Royal Soc 276:1679-1683
111. Barrett EL, Richardson DS (2011) Sex differences in telomeres and lifespan. Aging Cell 10:913-921
112. Kyo S, Takakura M, Kanaya T, Zhuo W, Fujimoto K, Nishio Y et al (1999) Estrogen activates telomerase. Cancer Res 59:5917-5921
113. Alonso-Alvarez C, Bertrand S, Faivre B, Chastel O, Sorci G (2007) Testosterone and oxidative stress: the oxidation handicap hypothesis. Proc Biol Sci Royal Soc 274:819-825
114. Vina J, Borras C, Gambini J, Sastre J, Pallardo FV (2005) Why females live longer than males: control of longevity by sex hormones. Sci Aging Knowledge Environ SAGE KE 2005:pe17
115. Tower J (2006) Sex-specific regulation of aging and apoptosis. Mech Ageing Dev 127:705-718
116. Camus MF, Clancy DJ, Dowling DK (2012) Mitochondria, maternal inheritance, and male aging. Curr Biol CB 22:1717-1721
117. Frank SA, Hurst LD (1996) Mitochondria and male disease. Nature 383:224
118. Gemmell NJ, Metcalf VJ, Allendorf FW (2004) Mother's curse: the effect of mtDNA on individual fitness and population viability. Trends Ecol Evol 19:238-244
119. Tower J, Arbeitman M (2009) The genetics of gender and life span. J Biol 8:38
120. Wolff JN, Gemmell NJ (2013) Mitochondria, maternal inheritance, and asymmetric fitness: why males die younger. BioEssays News Rev Mol Cell Develop Biol 35:93-99
121. Maklakov AA, Bonduriansky R, Brooks RC (2009) Sex differences, sexual selection, and ageing: an experimental evolution approach. Evol Int J Organic Evol 63:2491-2503
122. Lehto HR, Lehto S, Havulinna AS, Salomaa V (2013) Does the clinical spectrum of incident cardiovascular disease differ between men and women? Eur J Prev Cardiol 21:964-971
123. Intapad S, Ojeda NB, Dasinger JH, Alexander BT (2014) Sex differences in the developmental origins of cardiovascular disease. Physiology 29:122-132
124. Resanovic I, Rizzo M, Zafirovic S, Bjelogrlic P, Perovic M, Savic K et al. (2013) Anti-atherogenic effects of 17beta-estradiol. Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme 45: 701-708
125. Khalil RA (2013) Estrogen, vascular estrogen receptor and hormone therapy in postmenopausal vascular disease. Biochem Pharmacol 86:1627-1642
126. Asscheman H, Giltay EJ, Megens JA, de Ronde WP, van Trotsenburg MA, Gooren LJ (2011) A long-term follow-up study of mortality in transsexuals receiving treatment with cross-sex hormones. Eur J Endocrinol Eur Fed Endocr Soc 164:635-642
127. Zhao J, Zhu S, Sun L, Meng F, Zhao L, Zhao Y et al (2014) Androgen deprivation therapy for prostate cancer is associated with cardiovascular morbidity and mortality: a meta-analysis of population-based observational studies. PLoS One 9:e107516
128. Brooks MD, Sengupta R, Snyder SC, Rubin JB (2013) Hitting them where they live: targeting the glioblastoma perivascular stem cell niche. Curr Pathobiol Rep 1:101-110
129. Charles N, Ozawa T, Squatrito M, Bleau AM, Brennan CW, Hambardzumyan D et al (2010) Perivascular nitric oxide activates notch signaling and promotes stem-like character in PDGF-induced glioma cells. Cell Stem Cell 6:141-152
130. Arnold AP (2012) The end of gonad-centric sex determination in mammals. Trends in Genet TIG 28:55-61
131. Barker DJ (2004) Developmental origins of adult health and disease. J Epidemiol Community Health 58:114-115
132. Tsunoda Y, Tokunaga T, Sugie T (1985) Altered sex ratio of live young after transfer of fast- and slow-developing mouse embryos. Gamete Res 12:301-304
133. Ray PF, Conaghan J, Winston RM, Handyside AH (1995) Increased number of cells and metabolic activity in male human preimplantation embryos following in vitro fertilization. J Reprod Fertil 104:165-171
134. Gutierrez-Adan A, Perez-Crespo M, Fernandez-Gonzalez R, Ramirez MA, Moreira P, Pintado B et al (2006) Developmental consequences of sexual dimorphism during pre-implantation embryonic development. Reprod Domestic Animals Zuchthygiene 41(Suppl 2):54-62
135. Tagirov M, Rutkowska J (2014) Sexual dimorphism in the early embryogenesis in zebra finches. PLoS One 9:e114625
136. Tiffin GJ, Rieger D, Betteridge KJ, Yadav BR, King WA (1991) Glucose and glutamine metabolism in pre-attachment cattle embryos in relation to sex and stage of development. J Reprod Fertil 93:125-132
137. Gutierrez-Adan A, Granados J, Pintado B, De La Fuente J (2001) Influence of glucose on the sex ratio of bovine IVM/IVF embryos cultured in vitro. Reprod Fertil Dev 13:361-365
138. Bermejo-Alvarez P, Rizos D, Rath D, Lonergan P, Gutierrez-Adan A (2008) Epigenetic differences between male and female bovine blastocysts produced in vitro. Physiol Genomics 32:264-272
139. Van Blerkom J (2008) Mitochondria as regulatory forces in oocytes, preimplantation embryos and stem cells. Reprod Biomed Online 16:553-569
140. Bredbacka K, Bredbacka P (1996) Glucose controls sex-related growth rate differences of bovine embryos produced in vitro. J Reprod Fertil 106:169-172
141. Krietsch WK, Fundele R, Kuntz GW, Fehlau M, Burki K, Illmensee K (1982) The expression of X-linked phosphoglycerate kinase in the early mouse embryo. Differentiation Res Biol Diver 23:141-144
142. Williams TJ (1986) A technique for sexing mouse embryos by a visual colorimetric assay of the X-linked enzyme, glucose 6-phosphate dehydrogenase. Theriogenology 25:733-739
143. Kimura K, Iwata H, Thompson JG (2008) The effect of glucosamine concentration on the development and sex ratio of bovine embryos. Animal Reprod Sci 103:228-238
144. Gardner DK, Leese HJ (1987) Assessment of embryo viability prior to transfer by the noninvasive measurement of glucose uptake. J Exp Zool 242:103-105
145. Burgoyne PS (1993) A Y-chromosomal effect on blastocyst cell number in mice. Development 117:341-345
146. Pergament E, Fiddler M, Cho N, Johnson D, Holmgren WJ (1994) Sexual differentiation and preimplantation cell growth. Hum Reprod 9:1730-1732
147. Kishton RJ, Rathmell JC (2015) Novel therapeutic targets of tumor metabolism. Cancer J 21:62-69
148. Khulan B, Cooper WN, Skinner BM, Bauer J, Owens S, Prentice AM et al (2012) Periconceptional maternal micronutrient supplementation is associated with widespread gender related changes in the epigenome: a study of a unique resource in the Gambia. Hum Mol Genet 21:2086-2101
149. McKay JA, Wong YK, Relton CL, Ford D, Mathers JC (2011) Maternal folate supply and sex influence gene-specific DNA methylation in the fetal gut. Mol Nutr Food Res 55:1717-1723
150. Baserga M, Kaur R, Hale MA, Bares A, Yu X, Callaway CW et al (2010) Fetal growth restriction alters transcription factor binding and epigenetic mechanisms of renal 11beta-hydroxysteroid dehydrogenase type 2 in a sex-specific manner. Am J Physiol Regul Integr Comp Physiol 299:R334-R342
151. Bermejo-Alvarez P, Rizos D, Rath D, Lonergan P, Gutierrez-Adan A (2010) Sex determines the expression level of one third of the actively expressed genes in bovine blastocysts. Proc Natl Acad Sci USA 107:3394-3399
152. Xu Q, Yang C, Du Y, Chen Y, Liu H, Deng M et al (2014) AMPK regulates histone H2B O-GlcNAcylation. Nucleic Acids Res 42:5594-5604
153. Forma E, Jozwiak P, Brys M, Krzeslak A (2014) The potential role of O-GlcNAc modification in cancer epigenetics. Cell Mol Biol Lett 19:438-460
154. Van der Meulen J, Speleman F, Van Vlierberghe P (2014) The H3K27me3 demethylase UTX in normal development and disease. Epigenetics Off J DNA Methyl Soc 9:658-668
155. Greenfield A, Carrel L, Pennisi D, Philippe C, Quaderi N, Siggers P et al (1998) The UTX gene escapes X inactivation in mice and humans. Hum Mol Genet 7:737-742
156. Walport LJ, Hopkinson RJ, Vollmar M, Madden SK, Gileadi C, Oppermann U et al (2014) Human UTY(KDM6C) is a male-specific N-methyl lysyl demethylase. J Biol Chem 289:18302-18313
157. Van der Meulen J, Sanghvi V, Mavrakis K, Durinck K, Fang F, Matthijssens F et al (2015) The H3K27me3 demethylase UTX is a gender-specific tumor suppressor in T-cell acute lymphoblastic leukemia. Blood 125:13-21
158. Brockdorff N (2011) Chromosome silencing mechanisms in X-chromosome inactivation: unknown unknowns. Development 138:5057-5065
159. Chaligne R, Heard E (2014) X-chromosome inactivation in development and cancer. FEBS Lett 588:2514-2522
160. Arthold S, Kurowski A, Wutz A (2011) Mechanistic insights into chromosome-wide silencing in X inactivation. Hum Genet 130:295-305
161. Deng X, Berletch JB, Nguyen DK, Disteche CM (2014) X chromosome regulation: diverse patterns in development, tissues and disease. Nat Rev Genet 15:367-378
162. Deuve JL, Avner P (2011) The coupling of X-chromosome inactivation to pluripotency. Annu Rev Cell Dev Biol 27:611-629
163. Yildirim E, Kirby JE, Brown DE, Mercier FE, Sadreyev RI, Scadden DT et al (2013) Xist RNA is a potent suppressor of hematologic cancer in mice. Cell 152:727-742
164. Gabory A, Ferry L, Fajardy I, Jouneau L, Gothie JD, Vige A et al (2012) Maternal diets trigger sex-specific divergent trajectories of gene expression and epigenetic systems in mouse placenta. PLoS One 7:e47986
165. Barker DJ, Lampl M, Roseboom T, Winder N (2012) Resource allocation in utero and health in later life. Placenta 33(Suppl 2):e30-e34
166. Stark MJ, Dierkx L, Clifton VL, Wright IM (2006) Alterations in the maternal peripheral microvascular response in pregnancies complicated by preeclampsia and the impact of fetal sex. J Soc Gynecol Investig 13:573-578
167. Stark MJ, Clifton VL, Wright IM (2009) Neonates born to mothers with preeclampsia exhibit sex-specific alterations in microvascular function. Pediatr Res 65:292-295
168. Borzsonyi B, Demendi C, Nagy Z, Toth K, Csanad M, Pajor A et al (2011) Gene expression patterns of insulin-like growth factor 1, insulin-like growth factor 2 and insulin-like growth factor binding protein 3 in human placenta from pregnancies with intrauterine growth restriction. J Perinat Med 39:701-707
169. Scott NM, Hodyl NA, Murphy VE, Osei-Kumah A, Wyper H, Hodgson DM et al (2009) Placental cytokine expression covaries with maternal asthma severity and fetal sex. J Immunol 182:1411-1420
170. Goldenberg RL, Andrews WW, Faye-Petersen OM, Goepfert AR, Cliver SP, Hauth JC (2006) The Alabama Preterm Birth Study: intrauterine infection and placental histologic findings in preterm births of males and females less than 32 weeks. Am J Obstet Gynecol 195:1533-1537
171. Howerton CL, Morgan CP, Fischer DB, Bale TL (2013) O-GlcNAc transferase (OGT) as a placental biomarker of maternal stress and reprogramming of CNS gene transcription in development. Proc Natl Acad Sci USA 110:5169-5174
172. Phoenix CH, Goy RW, Gerall AA, Young WC (1959) Organizing action of prenatally administered testosterone propionate on the tissues mediating mating behavior in the female guinea pig. Endocrinology 65:369-382
173. McCarthy MM (2008) Estradiol and the developing brain. Physiol Rev 88:91-124
174. Giedd JN, Raznahan A, Mills KL, Lenroot RK (2012) Review: magnetic resonance imaging of male/female differences in human adolescent brain anatomy. Biol Sex Differ 3:19
175. Tiemeier H, Lenroot RK, Greenstein DK, Tran L, Pierson R, Giedd JN (2010) Cerebellum development during childhood and adolescence: a longitudinal morphometric MRI study. NeuroImage 49:63-70
176. Belcher SM (2009) Blockade of estrogen receptor signaling to improve outlook for medulloblastoma sufferers. Future Oncol 5:751-754
177. Mancuso M, Leonardi S, Ceccarelli M, Pasquali E, De Stefano I, Prisco MG et al (2010) Protective role of 17 beta-estradiol on medulloblastoma development in Patched 1 heterozygous mice. Int J Cancer J Int du Cancer 127:2749-2757
178. Cookman CJ, Belcher SM (2015) Estrogen Receptor beta Upregulates IGF1R Expression and Activity to Inhibit Apoptosis and Increase Growth of Medulloblastoma. Endocrinology en20151141
179. Schedin P (2006) Pregnancy-associated breast cancer and metastasis. Nat Rev Cancer 6:281-291
180. Fugazzola L, Cirello V, Beck-Peccoz P (2011) Fetal microchimerism as an explanation of disease. Nature Rev Endocrinol 7:89-97
181. Kamper-Jorgensen M, Biggar RJ, Tjonneland A, Hjalgrim H, Kroman N, Rostgaard K et al (2012) Opposite effects of microchimerism on breast and colon cancer. Eur J Cancer 48:2227-2235
182. Cirello V, Perrino M, Colombo C, Muzza M, Filopanti M, Vicentini L et al (2010) Fetal cell microchimerism in papillary thyroid cancer: studies in peripheral blood and tissues. Int J Cancer J Int du Cancer 126:2874-2878
183. Nguyen Huu S, Oster M, Avril MF, Boitier F, Mortier L, Richard MA et al. (2009) Fetal microchimeric cells participate in tumour angiogenesis in melanomas occurring during pregnancy. Am J Pathol 174: 630-7
184. Dubernard G, Oster M, Chareyre F, Antoine M, Rouzier R, Uzan S et al (2009) Increased fetal cell microchimerism in high grade breast carcinomas occurring during pregnancy. Int J Cancer J Int du Cancer 124:1054-1059
185. Gadi VK, Nelson JL (2007) Fetal microchimerism in women with breast cancer. Cancer Res 67:9035-9038
186. Crespi BJ, Summers K (2006) Positive selection in the evolution of cancer. Biol Rev Camb Philos Soc 81:407-424
187. Tomasetti C, Vogelstein B (2015) Cancer etiology. Variation in cancer risk among tissues can be explained by the number of stem cell divisions. Science 347:78-81
188. CBTRUS (2010) CBTRUS statistical report: primary brain and central nervous System tumors diagnosed in the United States in 2004-2006
189. Leroi AM, Koufopanou V, Burt A (2003) Cancer selection. Nature Rev Cancer 3:226-231
190. Coetzee G, Irvine R (2002) Size of the androgen receptor CAG repeat and prostate cancer: does it matter? J Clin Oncol 20:3572-3573
191. Adler MI, Bonduriansky R (2014) Sexual conflict, life span, and aging. Cold Spring Harbor Persp Biology 6
192. Edmondson RJ, Monaghan JM, Davies BR (2002) The human ovarian surface epithelium is an androgen responsive tissue. Br J Cancer 86:879-885
193. Ilekis JV, Connor JP, Prins GS, Ferrer K, Niederberger C, Scoccia B (1997) Expression of epidermal growth factor and androgen receptors in ovarian cancer. Gynecol Oncol 66:250-254
194. Silva EG, Tornos C, Fritsche HA, Jr., el-Naggar A, Gray K, Ordonez NG et al. (1997) The induction of benign epithelial neoplasms of the ovaries of guinea pigs by testosterone stimulation: a potential animal model. Modern Pathol Off J US Can Acad Pathol Inc 10: 879-883
195. Risch HA (1998) Hormonal etiology of epithelial ovarian cancer, with a hypothesis concerning the role of androgens and progesterone. J Natl Cancer Inst 90:1774-1786
196. Smith NG, Hurst LD (1998) Molecular evolution of an imprinted gene: repeatability of patterns of evolution within the mammalian insulin-like growth factor type II receptor. Genetics 150:823-833
197. Giovannucci E (2003) Nutrition, insulin, insulin-like growth factors and cancer. Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme 35: 694-704
198. Tycko B, Morison IM (2002) Physiological functions of imprinted genes. J Cell Physiol 192:245-258
199. Hernandez L, Kozlov S, Piras G, Stewart CL (2003) Paternal and maternal genomes confer opposite effects on proliferation, cell-cycle length, senescence, and tumor formation. Proc Natl Acad Sci USA 100:13344-13349
200. Bloom HJ, Peckham MJ, Richardson AE, Alexander PA, Payne PM (1973) Glioblastoma multiforme: a controlled trial to assess the value of specific active immunotherapy in patients treated by radical surgery and radiotherapy. Br J Cancer 27:253-267
201. Amlin-Van Schaick JC, Kim S, DiFabio C, Lee MH, Broman KW, Reilly KM (2012) Arlm1 is a male-specific modifier of astrocytoma resistance on mouse Chr 12. Neuro-oncology 14:160-174
202. Reilly KM, Tuskan RG, Christy E, Loisel DA, Ledger J, Bronson RT et al (2004) Susceptibility to astrocytoma in mice mutant for Nf1 and Trp53 is linked to chromosome 11 and subject to epigenetic effects. Proc Natl Acad Sci USA 101:13008-13013
203. Walrath JC, Fox K, Truffer E (2009) Gregory Alvord W, Quinones OA, Reilly KM. Chr 19(A/J) modifies tumor resistance in a sex- and parent-of-origin-specific manner. Mamm Genome 20:214-223
204. Zhu Y, Guignard F, Zhao D, Liu L, Burns DK, Mason RP et al (2005) Early inactivation of p53 tumor suppressor gene cooperating with NF1 loss induces malignant astrocytoma. Cancer Cell 8:119-130
205. Plunkett RJ, Lis A, Barone TA, Fronckowiak MD, Greenberg SJ (1999) Hormonal effects on glioblastoma multiforme in the nude rat model. J Neurosurg 90:1072-1077
206. Sareddy GR, Nair BC, Gonugunta VK, Zhang QG, Brenner A, Brann DW et al (2012) Therapeutic significance of estrogen receptor beta agonists in gliomas. Mol Cancer Ther 11:1174-1182
207. Arnold AP, Chen X (2009) What does the "four core genotypes" mouse model tell us about sex differences in the brain and other tissues? Front Neuroendocrinol 30:1-9
208. Arnold AP (2014) Conceptual frameworks and mouse models for studying sex differences in physiology and disease: why compensation changes the game. Exp Neurol 259:2-9
209. Wolstenholme JT, Rissman EF, Bekiranov S (2013) Sexual differentiation in the developing mouse brain: contributions of sex chromosome genes. Genes Brain Behav 12:166-180
210. Werler S, Poplinski A, Gromoll J, Wistuba J (2011) Expression of selected genes escaping from X inactivation in the 41, XX(Y) mouse model for Klinefelter's syndrome. Acta Paediatr 100:885-891
211. Case LK, Wall EH, Dragon JA, Saligrama N, Krementsov DN, Moussawi M et al (2013) The Y chromosome as a regulatory element shaping immune cell transcriptomes and susceptibility to autoimmune disease. Genome Res 23:1474-1485
212. Do TN, Ucisik-Akkaya E, Davis CF, Morrison BA, Dorak MT (2009) TP53 R72P and MDM2 SNP309 polymorphisms in modification of childhood acute lymphoblastic leukemia susceptibility. Cancer Genet Cytogenet 195:31-36
213. Firoz EF, Warycha M, Zakrzewski J, Pollens D, Wang G, Shapiro R et al (2009) Association of MDM2 SNP309, age of onset, and gender in cutaneous melanoma. Clin Cancer Res 15:2573-2580
214. Bond GL, Hirshfield KM, Kirchhoff T, Alexe G, Bond EE, Robins H et al (2006) MDM2 SNP309 accelerates tumor formation in a gender-specific and hormone-dependent manner. Cancer Res 66:5104-5110