Skip to main content

Advertisement

Log in

Pregnancy and multiple sclerosis: from molecular mechanisms to clinical application

  • Review
  • Published:
Seminars in Immunopathology Aims and scope Submit manuscript

Abstract

Translational research generally refers to a “bench to bedside” approach where basic science discoveries in models move to clinical trials in humans. However, a “bedside to bench to bedside” approach may be more promising with respect to clinical relevance, since it starts with a clinical observation that can serve as a research paradigm to elucidate mechanisms and translate them back into novel therapeutic approaches. The effect of pregnancy on human autoimmune disorders in general, and multiple sclerosis (MS) in particular, serves as an intriguing example of how this can be used to understand disease pathobiology and discover new therapeutic targets. Disease activity in MS undergoes pronounced shifts in the time before, during, and after pregnancy. The most well-known and established example is a reduction in relapse rates in the last trimester by 70–80 %. However, disease activity reappears in the first few months after delivery, temporarily overshooting pre-pregnancy levels. This phenomenon has since its first description served as a model for investigating novel treatment options in animal models and has cumulated in successful phase 2a and 2b trials in female MS patients. However, recently, a number of other clinical observations have been made that might be similarly suitable to offer additional insights into pathobiological mechanisms of MS activity, progression, and possibly even incidence. Here, we outline the various changes in the clinical course of MS that have been described in relation to pregnancy, both short term and long term, and discuss how these may inform the development of novel treatments for autoimmune diseases.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Libert C, Dejager L, Pinheiro I (2010) The X chromosome in immune functions: when a chromosome makes the difference. Nat Rev Immunol 10(8):594–604

    Article  CAS  PubMed  Google Scholar 

  2. Whitacre CC, Reingold SC, O'Looney PA (1999) A gender gap in autoimmunity. Science 283(5406):1277–1278

    Article  CAS  PubMed  Google Scholar 

  3. Hellwig K, Haghikia A, Gold R (2010) Parenthood and immunomodulation in patients with multiple sclerosis. J Neurol 257(4):580–583

    Article  CAS  PubMed  Google Scholar 

  4. Vukusic S, Marignier R (2015) Multiple sclerosis and pregnancy in the ‘treatment era’. Nat Rev Neurol 11(5):280–289

    Article  PubMed  Google Scholar 

  5. Coyle PK (2016) Management of women with multiple sclerosis through pregnancy and after childbirth. Ther Adv Neurol Disord 9(3):198–210

    Article  PubMed  PubMed Central  Google Scholar 

  6. Sawcer S, Franklin RJ, Ban M (2014) Multiple sclerosis genetics. Lancet Neurol 13(7):700–709

    Article  CAS  PubMed  Google Scholar 

  7. Ascherio A (2013) Environmental factors in multiple sclerosis. Expert Rev Neurother 13(12 Suppl):3–9

    Article  PubMed  Google Scholar 

  8. Dendrou CA, Fugger L, Friese MA (2015) Immunopathology of multiple sclerosis. Nat Rev Immunol 15(9):545–558

    Article  CAS  PubMed  Google Scholar 

  9. Friese MA, Schattling B, Fugger L (2014) Mechanisms of neurodegeneration and axonal dysfunction in multiple sclerosis. Nat Rev Neurol 10(4):225–238

    Article  CAS  PubMed  Google Scholar 

  10. B. Runmarker, O. Andersen, (1995) Pregnancy is associated with a lower risk of onset and a better prognosis in multiple sclerosis [see comments], Brain 118(Pt 1)(10):253–61

  11. Villard-Mackintosh L, Vessey MP (1993) Oral contraceptives and reproductive factors in multiple sclerosis incidence. Contraception 47(2):161–168

    Article  CAS  PubMed  Google Scholar 

  12. Thorogood M, Hannaford PC (1998) The influence of oral contraceptives on the risk of multiple sclerosis. Br J Obstet Gynaecol 105(12):1296–1299

    Article  CAS  PubMed  Google Scholar 

  13. Alonso A, Jick SS, Olek MJ, Ascherio A, Jick H, Hernan MA (2005) Recent use of oral contraceptives and the risk of multiple sclerosis. Arch Neurol 62(9):1362–1365

    Article  PubMed  Google Scholar 

  14. Hernan MA, Hohol MJ, Olek MJ, Spiegelman D, Ascherio A (2000) Oral contraceptives and the incidence of multiple sclerosis. Neurology 55(6):848–854

    Article  CAS  PubMed  Google Scholar 

  15. Weinshenker BG, Hader W, Carriere W, Baskerville J, Ebers GC (1989) The influence of pregnancy on disability from multiple sclerosis: a population-based study in Middlesex County, Ontario. Neurology 39(11):1438–1440

    Article  CAS  PubMed  Google Scholar 

  16. Ponsonby AL, Lucas RM, van der Mei IA, Dear K, Valery PC, Pender MP, Taylor BV, Kilpatrick TJ, Coulthard A, Chapman C, Williams D, McMichael AJ, Dwyer T (2012) Offspring number, pregnancy, and risk of a first clinical demyelinating event: the AusImmune Study. Neurology 78(12):867–874

    Article  PubMed  Google Scholar 

  17. Laplaud DA, Leray E, Barriere P, Wiertlewski S, Moreau T (2006) Increase in multiple sclerosis relapse rate following in vitro fertilization. Neurology 66(8):1280–1281

    Article  PubMed  Google Scholar 

  18. Michel L, Foucher Y, Vukusic S, Confavreux C, de Seze J, Brassat D, Clanet M, Clavelou P, Ouallet JC, Brochet B, Pelletier J, Labauge P, Lebrun C, Lepage E, Le Frere F, Jacq-Foucher M, Barriere P, Wiertlewski S, Laplaud DA (2012) Club Francophone de la Sclerose En, increased risk of multiple sclerosis relapse after in vitro fertilisation. J Neurol Neurosurg Psychiatry 83(8):796–802

    Article  PubMed  Google Scholar 

  19. Hellwig K, Beste C, Brune N, Haghikia A, Muller T, Schimrigk S, Gold R (2008) Increased MS relapse rate during assisted reproduction technique. J Neurol 255(4):592–593

    Article  PubMed  Google Scholar 

  20. Hellwig K, Schimrigk S, Beste C, Muller T, Gold R (2009) Increase in relapse rate during assisted reproduction technique in patients with multiple sclerosis. Eur Neurol 61(2):65–68

    Article  PubMed  Google Scholar 

  21. Correale J, Farez MF, Ysrraelit MC (2012) Increase in multiple sclerosis activity after assisted reproduction technology. Ann Neurol 72(5):682–694

    Article  CAS  PubMed  Google Scholar 

  22. Pasch LA, Gregorich SE, Katz PK, Millstein SG, Nachtigall RD, Bleil ME, Adler NE (2012) Psychological distress and in vitro fertilization outcome. Fertil Steril 98(2):459–464

    Article  PubMed  PubMed Central  Google Scholar 

  23. Mohr DC, Hart SL, Julian L, Cox D, Pelletier D (2004) Association between stressful life events and exacerbation in multiple sclerosis: a meta-analysis. BMJ 328(7442):731

    Article  PubMed  PubMed Central  Google Scholar 

  24. Golan D, Somer E, Dishon S, Cuzin-Disegni L, Miller A (2008) Impact of exposure to war stress on exacerbations of multiple sclerosis. Ann Neurol 64(2):143–148

    Article  PubMed  Google Scholar 

  25. Gold SM, Sasidhar MV, Lagishetty V, Spence RD, Umeda E, Ziehn MO, Krieger T, Schulz KH, Heesen C, Hewison M, Voskuhl RR (2012) Dynamic development of glucocorticoid resistance during autoimmune neuroinflammation. J Clin Endocrinol Metab 97(8):E1402–E1410

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Gold SM, Mohr DC, Huitinga I, Flachenecker P, Sternberg EM, Heesen C (2005) The role of stress-response systems for the pathogenesis and progression of MS. Trends Immunol 26(12):644–652

    Article  CAS  PubMed  Google Scholar 

  27. Confavreux C, Hutchinson M, Hours MM, Cortinovis-Tourniaire P, Moreau T (1998) Rate of pregnancy-related relapse in multiple sclerosis. Pregnancy in multiple sclerosis group [see comments]. N Engl J Med 339(5):285–291

    Article  CAS  PubMed  Google Scholar 

  28. Finkelsztejn A, Brooks JB, Paschoal FM Jr, Fragoso YD (2011) What can we really tell women with multiple sclerosis regarding pregnancy? A systematic review and meta-analysis of the literature. BJOG 118(7):790–797

    Article  CAS  PubMed  Google Scholar 

  29. Hutchinson M (2013) One can prevent post-partum MS relapses by exclusive breast feeding: commentary. Mult Scler 19(12):1569–1570

    Article  PubMed  Google Scholar 

  30. Langer-Gould A, Hellwig K (2013) One can prevent post-partum MS relapses by exclusive breast feeding: yes. Mult Scler 19(12):1567–1568

    Article  PubMed  Google Scholar 

  31. Vukusic S, Confavreux C (2013) One can prevent post-partum MS relapses by exclusive breast feeding: no. Mult Scler 19(12):1565–1566

    Article  PubMed  Google Scholar 

  32. Vukusic S, Hutchinson M, Hours M, Moreau T, Cortinovis-Tourniaire P, Adeleine P, Confavreux C (2004) The pregnancy in multiple sclerosis, pregnancy and multiple sclerosis (the PRIMS study): clinical predictors of post-partum relapse. Brain 127(Pt 6):1353–1360

    Article  PubMed  Google Scholar 

  33. Nelson LM, Franklin GM, Jones MC (1988) Risk of multiple sclerosis exacerbation during pregnancy and breast-feeding. JAMA 259(23):3441–3443

    Article  CAS  PubMed  Google Scholar 

  34. Airas L, Jalkanen A, Alanen A, Pirttila T, Marttila RJ (2010) Breast-feeding, postpartum and prepregnancy disease activity in multiple sclerosis. Neurology 75(5):474–476

    Article  CAS  PubMed  Google Scholar 

  35. Portaccio E, Ghezzi A, Hakiki B, Martinelli V, Moiola L, Patti F, La Mantia L, Mancardi GL, Solaro C, Tola MR, Pozzilli C, De Giglio L, Totaro R, Lugaresi A, De Luca G, Paolicelli D, Marrosu MG, Comi G, Trojano M, Amato MP (2011) Breastfeeding is not related to postpartum relapses in multiple sclerosis. Neurology 77(2):145–150

    Article  CAS  PubMed  Google Scholar 

  36. A. Langer-Gould, S.M. Huang, R. Gupta, A.D. Leimpeter, E. Greenwood, K.B. Albers, S.K. Van Den Eeden, L.M. Nelson (2009) Exclusive breastfeeding and the risk of postpartum relapses in women with multiple sclerosis. Arch Neurol 66(8):958–963

  37. Hellwig K, Haghikia A, Agne H, Beste C, Gold R (2009) Protective effect of breastfeeding in postpartum relapse rate of mothers with multiple sclerosis. Arch Neurol 66(12):1580–1581 author reply 1581

    Article  PubMed  Google Scholar 

  38. Hellwig K, Rockhoff M, Herbstritt S, Borisow N, Haghikia A, Elias-Hamp B, Menck S, Gold R, Langer-Gould A (2015) Exclusive breastfeeding and the effect on postpartum multiple sclerosis relapses. JAMA Neurol 72(10):1132–1138

    Article  PubMed  Google Scholar 

  39. Patas K, Engler JB, Friese MA, Gold SM (2013) Pregnancy and multiple sclerosis: feto-maternal immune cross talk and its implications for disease activity. J Reprod Immunol 97(1):140–146

    Article  CAS  PubMed  Google Scholar 

  40. Langer-Gould A, Garren H, Slansky A, Ruiz PJ, Steinman L (2002) Late pregnancy suppresses relapses in experimental autoimmune encephalomyelitis: evidence for a suppressive pregnancy-related serum factor. J Immunol 169(2):1084–1091

    Article  CAS  PubMed  Google Scholar 

  41. Abramsky O, Brenner T, Mizrachi R, Soffer D (1982) Alpha-fetoprotein suppresses experimental allergic encephalomyelitis. J Neuroimmunol 2(1):1–7

    Article  CAS  PubMed  Google Scholar 

  42. Laffont S, Garnier L, Lelu K, Guery JC (2015) Estrogen-mediated protection of experimental autoimmune encephalomyelitis: lessons from the dissection of estrogen receptor-signaling in vivo. Biomed J 38(3):194–205

    Article  PubMed  Google Scholar 

  43. Kim S, Liva SM, Dalal MA, Verity MA, Voskuhl RR (1999) Estriol ameliorates autoimmune demyelinating disease: implications for multiple sclerosis. Neurology 52(6):1230–1238

    Article  CAS  PubMed  Google Scholar 

  44. Yates MA, Li Y, Chlebeck P, Proctor T, Vandenbark AA, Offner H (2010) Progesterone treatment reduces disease severity and increases IL-10 in experimental autoimmune encephalomyelitis. J Neuroimmunol 220(1–2):136–139

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Hoffman GE, Le WW, Murphy AZ, Koski CL (2001) Divergent effects of ovarian steroids on neuronal survival during experimental allergic encephalitis in Lewis rats. Exp Neurol 171(2):272–284

    Article  CAS  PubMed  Google Scholar 

  46. Garay L, Gonzalez Deniselle MC, Gierman L, Meyer M, Lima A, Roig P, De Nicola AF (2008) Steroid protection in the experimental autoimmune encephalomyelitis model of multiple sclerosis. Neuroimmunomodulation 15(1):76–83

    CAS  PubMed  Google Scholar 

  47. Garay L, Deniselle MC, Lima A, Roig P, De Nicola AF (2007) Effects of progesterone in the spinal cord of a mouse model of multiple sclerosis. J Steroid Biochem Mol Biol 107(3–5):228–237

    Article  CAS  PubMed  Google Scholar 

  48. Garay L, Deniselle MC, Meyer M, Costa JJ, Lima A, Roig P, De Nicola AF (2009) Protective effects of progesterone administration on axonal pathology in mice with experimental autoimmune encephalomyelitis. Brain Res 1283:177–185

    Article  CAS  PubMed  Google Scholar 

  49. Voskuhl RR, Gold SM (2012) Sex-related factors in multiple sclerosis susceptibility and progression. Nat Rev Neurol 8(5):255–263

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Nashold FE, Spach KM, Spanier JA, Hayes CE (2009) Estrogen controls vitamin D3-mediated resistance to experimental autoimmune encephalomyelitis by controlling vitamin D3 metabolism and receptor expression. J Immunol 183(6):3672–3681

    Article  CAS  PubMed  Google Scholar 

  51. Spanier JA, Nashold FE, Mayne CG, Nelson CD, Hayes CE (2015) Vitamin D and estrogen synergy in Vdr-expressing CD4(+) T cells is essential to induce Helios(+)FoxP3(+) T cells and prevent autoimmune demyelinating disease. J Neuroimmunol 286:48–58

    Article  CAS  PubMed  Google Scholar 

  52. Gilli F, Lindberg RL, Valentino P, Marnetto F, Malucchi S, Sala A, Capobianco M, di Sapio A, Sperli F, Kappos L, Calogero RA, Bertolotto A (2010) Learning from nature: pregnancy changes the expression of inflammation-related genes in patients with multiple sclerosis. PLoS One 5(1):e8962

    Article  PubMed  PubMed Central  Google Scholar 

  53. Al-Shammri S, Rawoot P, Azizieh F, AbuQoora A, Hanna M, Saminathan TR, Raghupathy R (2004) Th1/Th2 cytokine patterns and clinical profiles during and after pregnancy in women with multiple sclerosis. J Neurol Sci 222(1–2):21–27

    Article  CAS  PubMed  Google Scholar 

  54. Gilmore W, Arias M, Stroud N, Stek A, McCarthy KA, Correale J (2004) Preliminary studies of cytokine secretion patterns associated with pregnancy in MS patients. J Neurol Sci 224(1–2):69–76

    Article  CAS  PubMed  Google Scholar 

  55. Lopez C, Comabella M, Tintore M, Sastre-Garriga J, Montalban X (2006) Variations in chemokine receptor and cytokine expression during pregnancy in multiple sclerosis patients. Mult Scler 12(4):421–427

    Article  CAS  PubMed  Google Scholar 

  56. Airas L, Saraste M, Rinta S, Elovaara I, Huang YH, Wiendl H (2008) Immunoregulatory factors in multiple sclerosis patients during and after pregnancy: relevance of natural killer cells. Clin Exp Immunol 151(2):235–243

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Langer-Gould A, Gupta R, Huang S, Hagan A, Atkuri K, Leimpeter AD, Albers KB, Greenwood E, Van Den Eeden SK, Steinman L, Nelson LM (2010) Interferon-gamma-producing T cells, pregnancy, and postpartum relapses of multiple sclerosis. Arch Neurol 67(1):51–57

    Article  PubMed  Google Scholar 

  58. Neuteboom RF, Verbraak E, Voerman JS, van Meurs M, Steegers EA, de Groot CJ, Laman JD, Hintzen RQ (2009) First trimester interleukin 8 levels are associated with postpartum relapse in multiple sclerosis. Mult Scler 15(11):1356–1358

    Article  CAS  PubMed  Google Scholar 

  59. Sanchez-Ramon S, Navarro AJ, Aristimuno C, Rodriguez-Mahou M, Bellon JM, Fernandez-Cruz E, de Andres C (2005) Pregnancy-induced expansion of regulatory T-lymphocytes may mediate protection to multiple sclerosis activity. Immunol Lett 96(2):195–201

    Article  CAS  PubMed  Google Scholar 

  60. Neuteboom RF, Verbraak E, Wierenga-Wolf AF, van Meurs M, Steegers EA, de Groot CJ, Laman JD, Hintzen RQ (2010) Pregnancy-induced fluctuations in functional T-cell subsets in multiple sclerosis patients. Mult Scler 16(9):1073–1078

    Article  CAS  PubMed  Google Scholar 

  61. Clark DA (2016) The importance of being a regulatory T cell in pregnancy. J Reprod Immunol 116:60–69

    Article  CAS  PubMed  Google Scholar 

  62. Erlebacher A (2013) Mechanisms of T cell tolerance towards the allogeneic fetus. Nat Rev Immunol 13(1):23–33

    Article  CAS  PubMed  Google Scholar 

  63. M.J. Polanczyk, C. Hopke, J. Huan, A.A. Vandenbark, H. Offner, (2005) Enhanced FoxP3 expression and Treg cell function in pregnant and estrogen-treated mice. J Neuroimmunol 170(1–2):85–92

  64. Munoz-Suano A, Kallikourdis M, Sarris M, Betz AG (2012) Regulatory T cells protect from autoimmune arthritis during pregnancy. J Autoimmun 38(2–3):J103–J108

    Article  CAS  PubMed  Google Scholar 

  65. D'Hooghe MB, De Keyser J (2014) Multiparity in women with multiple sclerosis causes less long-term disability: yes. Mult Scler 20(11):1432–1434

    Article  PubMed  Google Scholar 

  66. Hutchinson M (2014) Multiparity in women with multiple sclerosis causes less long-term disability: commentary. Mult Scler 20(11):1437–1438

    Article  PubMed  Google Scholar 

  67. McCombe PA, Callaway LK (2014) Multiparity in women with multiple sclerosis causes less long-term disability: no. Mult Scler 20(11):1435–1436

    Article  CAS  PubMed  Google Scholar 

  68. Roullet E, Verdier-Taillefer MH, Amarenco P, Gharbi G, Alperovitch A, Marteau R (1993) Pregnancy and multiple sclerosis: a longitudinal study of 125 remittent patients. J Neurol Neurosurg Psychiatry 56(10):1062–1065

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Damek DM, Shuster EA (1997) Pregnancy and multiple sclerosis. Mayo Clin Proc 72(10):977–989

    Article  CAS  PubMed  Google Scholar 

  70. Verdru P, Theys P, D'Hooghe MB, Carton H (1994) Pregnancy and multiple sclerosis: the influence on long term disability. Clin Neurol Neurosurg 96(1):38–41

    Article  CAS  PubMed  Google Scholar 

  71. D'Hooghe BM, Nagels G, Uitdehaag BM (2010) Long-term effects of childbirth in MS. J Neurol Neurosurg Psychiatry 81(1):38–41

    Article  PubMed  Google Scholar 

  72. Masera S, Cavalla P, Prosperini L, Mattioda A, Mancinelli CR, Superti G, Chiavazza C, Vercellino M, Pinessi L, Pozzilli C (2015) Parity is associated with a longer time to reach irreversible disability milestones in women with multiple sclerosis. Mult Scler 21(10):1291–1297

    Article  CAS  PubMed  Google Scholar 

  73. Rowe JH, Ertelt JM, Xin L, Way SS (2012) Pregnancy imprints regulatory memory that sustains anergy to fetal antigen. Nature 490:102–106

  74. Spence RD, Voskuhl RR (2012) Neuroprotective effects of estrogens and androgens in CNS inflammation and neurodegeneration. Front Neuroendocrinol 33(1):105–115

    Article  CAS  PubMed  Google Scholar 

  75. Munger KL, Aivo J, Hongell K, Soilu-Hanninen M, Surcel HM, Ascherio A (2016) Vitamin D status during pregnancy and risk of multiple sclerosis in offspring of women in the Finnish maternity cohort. JAMA Neurol 73(5):515–519

    Article  PubMed  Google Scholar 

  76. Lauritzen C (1987) Results of a 5 years prospective study of estriol succinate treatment in patients with climacteric complaints. Horm Metab Res 19(11):579–584

    Article  CAS  PubMed  Google Scholar 

  77. Schiff I, Wentworth B, Koos B, Ryan KJ, Tulchinsky D (1978) Effect of estriol administration on the hypogonadal woman. Fertil Steril 30(3):278–282

    Article  CAS  PubMed  Google Scholar 

  78. Sicotte NL, Liva SM, Klutch R, Pfeiffer P, Bouvier S, Odesa S, Wu TC, Voskuhl RR (2002) Treatment of multiple sclerosis with the pregnancy hormone estriol. Ann Neurol 52(4):421–428

    Article  CAS  PubMed  Google Scholar 

  79. Soldan SS, Retuerto AI, Sicotte NL, Voskuhl RR (2003) Immune modulation in multiple sclerosis patients treated with the pregnancy hormone estriol. J Immunol 171(11):6267–6274

    Article  CAS  PubMed  Google Scholar 

  80. Gold SM, Sasidhar MV, Morales LB, Du S, Sicotte NL, Tiwari-Woodruff SK, Voskuhl RR (2009) Estrogen treatment decreases matrix metalloproteinase (MMP)-9 in autoimmune demyelinating disease through estrogen receptor alpha (ERalpha). Lab Investig 89(10):1076–1083

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Voskuhl RR, Wang H, Wu TC, Sicotte NL, Nakamura K, Kurth F, Itoh N, Bardens J, Bernard JT, Corboy JR, Cross AH, Dhib-Jalbut S, Ford CC, Frohman EM, Giesser B, Jacobs D, Kasper LH, Lynch S, Parry G, Racke MK, Reder AT, Rose J, Wingerchuk DM, MacKenzie-Graham AJ, Arnold DL, Tseng CH, Elashoff R (2016) Estriol combined with glatiramer acetate for women with relapsing-remitting multiple sclerosis: a randomised, placebo-controlled, phase 2 trial. Lancet Neurol 15(1):35–46

    Article  CAS  PubMed  Google Scholar 

  82. Voskuhl R, Wang H, Elashoff RM (2016) Why use sex hormones in relapsing-remitting multiple sclerosis?—Authors’ reply. Lancet Neurol 15(8):790–791

    Article  PubMed  Google Scholar 

  83. Pozzilli C, De Giglio L, Barletta VT, Marinelli F, Angelis FD, Gallo V, Pagano VA, Marini S, Piattella MC, Tomassini V, Pantano P (2015) Oral contraceptives combined with interferon β in multiple sclerosis. Neurol Neuroimmunol Neuroinflamm 2(4):e120

  84. Schumacher M, Mattern C, Ghoumari A, Oudinet JP, Liere P, Labombarda F, Sitruk-Ware R, De Nicola AF, Guennoun R (2014) Revisiting the roles of progesterone and allopregnanolone in the nervous system: resurgence of the progesterone receptors. Prog Neurobiol 113:6–39

    Article  CAS  PubMed  Google Scholar 

  85. Voskuhl RR (2012) Assisted reproduction technology in multiple sclerosis: giving birth to a new avenue of research in hormones and autoimmunity. Ann Neurol 72(5):631–632

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Stefan M. Gold or Rhonda R. Voskuhl.

Additional information

This article is a contribution to the special issue on Fetomaternal Cross Talk and Its Effect on Pregnancy Maintenance, Maternal and Offspring Health - Guest Editor: Petra Arck

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Gold, S.M., Voskuhl, R.R. Pregnancy and multiple sclerosis: from molecular mechanisms to clinical application. Semin Immunopathol 38, 709–718 (2016). https://doi.org/10.1007/s00281-016-0584-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00281-016-0584-y

Keywords

Navigation