Low maternal progesterone may contribute to both obstetrical complications and autism

Medical Hypotheses

Volumn 82, Issue 3, 2014, Pages 313-318

  Whitaker Azmitia, Patricia M ^a   Lobel, Marci ^a   Moyer, Anne ^a  

^a STONY BROOK UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AUTISTIC DISORDER; BRAIN; FEMALE; HUMANS; LABOR, OBSTETRIC; MALE; PREGNANCY; PREGNANCY COMPLICATIONS; PROGESTERONE;

EID: 84893898619     PISSN: 03069877     EISSN: 15322777     Source Type: Journal    
DOI: 10.1016/j.mehy.2013.12.018     Document Type: Article

References (102)

1. Hertz-Picciotto I., Delwiche L. The rise in autism and the role of age at diagnosis. Epidemiology 2009, 20:84-90.
2. Deykin E.Y., MacMahon B. Pregnancy, delivery, and neonatal complications among autistic children. Am J Dis Child 1980, 134:860-864.
3. Hill M., Parízek A., Jirásek J.E., Jirkovská M., Dusková M., Klímková M., et al. Is maternal progesterone actually independent of the fetal steroids?. Physiol Res 2010, 59:211-224.
4. Chamak B. Autism: overestimation of the genetic origins. Med Sci (Paris) 2010, 26:659-662.
5. Gronborg T.K., Schendel D.E., Parner E.T. Recurrence of autism spectrum disorders in full- and half-siblings and trends over time: a population-based cohort study. JAMA Pediatr 2013, 167:947-953.
6. H.V. Bohm, M.G. Stewart,.M. Healy. On the autistic spectrum disorder concordance rates of twins and non-twin siblings. Med Hypotheses. (2013) [Epub ahead of print].
7. Finegan J.A., Quarrington B. Pre-, peri-, and neonatal factors and infantile autism. J Child Psychol Psychiatry 1979, 20:119-128.
8. Gillberg C., Gillberg I.C. Infantile autism: a total population study of reduced optimality in the pre-, peri-, and neonatal period. J Autism Dev Disord 1983, 13:153-166.
9. Mason-Brothers A., Ritvo E.R., Guze B., et al. Pre-, peri-, and postnatal factors in 181 autistic patients from single and multiple incidence families. J Am Acad Child Adolesc Psychiatry 1987, 26:39-42.
10. Bolton P.F., Murphy M., Macdonald H., Whitlock B., Pickles A., Rutter M. Obstetric complications in autism: consequences or causes of the condition?. J Am Acad Child Adolesc Psychiatry 1997, 36:272-281.
11. Burd L., Severud R., Kerbeshian J., Klug G. Prenatal and perinatal risk factors for autism. J Perinat Med 1999, 27:441-450.
12. Juul-Dam N., Townsend J., Courchesne E. Prenatal, perinatal, and neonatal factors in autism, pervasive developmental disorder-not otherwise specified, and the general population. Pediatrics 2001, 107:E63.
13. Wilkerson D.S., Volpe A.G., Dean R.S., Titus J.B. Perinatal complications as predictors of infantile autism. Int J Neurosci 2002, 112:1085-1098.
14. Bilder D., Pinborough-Zimmerman J., Miller J., McMahon W. Prenatal, perinatal, and neonatal factors associated with autism spectrum disorders. Pediatrics 2009, 123:1293-1300.
15. Glasson E.J., Bower C., Petterson B., de Klerk N., Chaney G., Hallmayer J.F. Perinatal factors and the development of autism: a population study. Arch Gen Psychiatry 2004, 6:618-627.
16. Beversdorf D.Q., Manning S.E., Hillier A., et al. Timing of prenatal stressors and autism. J Autism Dev Disord 2005, 35:471-478.
17. Larsson H.J., Eaton W.W., Madsen K.M., et al. Risk factors for autism: perinatal factors, parental psychiatric history, and socioeconomic status. Am J Epidemiol 2005, 161:916-925.
18. Maimburg R.D., Vaeth M. Perinatal risk factors and infantile autism. Acta Psychiatr Scand 2006, 114:257-264.
19. Brimacombe M., Ming X., Lamendola X.M. Prenatal and birth complications in autism. Matern Child Health 2007, 11:73-79.
20. Burstyn I., Sithole F., Zwaigenbaum L. Autism spectrum disorders, maternal characteristics and obstetric complications among singletons born in Alberta, Canada. Chronic Dis Can 2010, 30:125-134.
21. Dodds L., Fell D.B., Shea S., Armson B.A., Allen C.A., Bryson S. The role of prenatal, obstetric and neonatal factors in the development of autism. J Autism Dev Disord 2011, 41:891-902.
22. Konno T., Graham A.R., Rempel L.A., et al. Subfertility linked to combined luteal insufficiency and uterine progesterone resistance. Endocrinology 2010, 151:4537-4550.
23. Young S.L., Lessey B.A. Progesterone function in human endometrium: clinical perspectives. Semin Reprod Med 2010, 28:5-16.
24. Wiebe E.R., Trussell J. Contraceptive failure related to estimated cycle day of conception relative to the start of the last bleeding episode. Contraception 2009, 79:178-181.
25. Krakowiak P., Walker C.K., Bremer A.A., et al. Maternal metabolic conditions and risk for autism and other neurodevelopmental disorders. Pediatrics 2012, 129:e1121-e1128.
26. Lagiou P., Lagiou A., Samoli E., Hsieh C.C., Adami H.O., Trichopoulos D. Diet during pregnancy and levels of maternal pregnancy hormones in relation to the risk of breast cancer in the offspring. Eur J Cancer Prev 2006, 15:20-26.
27. Szekeres-Bartho J., Reznikoff-Etievant M.F., Varga P., Pichon M.F., Varga Z., Chaouat G. Lymphocytic progesterone receptors in normal and pathological human pregnancy. J Reprod Immunol 1989, 16(3):239-247.
28. Haas D.M., Ramsey P.S. Progestogen for preventing miscarriage. Cochrane Database Syst Rev 2008, 2:CD003511.
29. Patterson P.H. Immune involvement in schizophrenia and autism: etiology, pathology and animal models. Behav Brain Res 2009, 204:313-321.
30. Patterson P.H. Maternal infection and immune involvement in autism. Trends Mol Med 2011, 17:389-394.
31. Zerbo O., Iosif A.M., Walker C., Ozonoff S., Hansen R.L., Hertz-Picciotto I. Is maternal influenza or fever during pregnancy associated with autism or developmental delays? Results from the CHARGE (CHildhood Autism Risks from Genetics and Environment) study. J Autism Dev Disord 2013, 43:25-33.
32. Atladóttir H.O., Thorsen P., Østergaard L., Schendel D.E., Lemcke S., Abdallah M., et al. Maternal infection requiring hospitalization during pregnancy and autism spectrum disorders. J Autism Dev Disord 2010, 40:1423-1430.
33. Bauman MD, Iosif AM, Smith SE, Bregere C, Amaral DG, Patterson PH. Activation of the maternal immune system during pregnancy alters behavioral development of rhesus monkey offspring. Biol Psychiatry 2013 [Epub ahead of print].
34. Vargas D.L., Nascimbene C., Krishnan C., Zimmerman A.W., Pardo C.A. Neuroglial activation and neuroinflammation in the brain of patients with autism. Ann Neurol 2005, 57:67-81.
35. Morgan J.T., Chana G., Pardo C.A., et al. Microglial activation and increased microglial density observed in the dorsolateral prefrontal cortex in autism. Biol Psychiatry 2010, 68(4):368-376.
36. Lee J.H., Ulrich B., Cho J., Park J., Kim C.H. Progesterone promotes differentiation of human cord blood fetal T cells into T regulatory cells but suppresses their differentiation into Th17 cells. J Immunol 2011, 187:1778-1787.
37. Wang J., Zhao Y., Liu C., Jiang C., Zhao C., Zhu Z. Progesterone inhibits inflammatory response pathways after permanent middle cerebral artery occlusion in rats. Mol Med Rep 2011, 4:319-324.
38. Hughes G.C., Clark E.A., Wong A. The intracellular pro-gesterone receptor regulates CD4+ T cells and Tcell-dependent anti-body responses. J Leukoc Biol 2013, 93:369-375.
39. Szekeres-Bartho J., Balasch J. Progestagen therapy for recurrent miscarriage. Hum Reprod Update 2008, 14:27-35.
40. Druckmann R., Druckmann M.A. Progesterone and the immunology of pregnancy. J Steroid Biochem Mol Biol 2005, 97(5):389-396.
41. Essa M.M., Braidy N., Vijayan K.R., Subash S., Guillemin G.J. Excitotoxicity in the pathogenesis of autism. Neurotox Res 2013, 23:393-400.
42. Wright D.W., Kellermann A.L., Hertzberg V.S., et al. ProTECT: a randomized clinical trial of progesterone for acute traumatic brain injury. Ann Emerg Med 2007, 49:391-402.
43. Xiao G., Wei J., Yan W., Wang W., Lu Z. Improved outcomes from the administration of progesterone for patients with acute severe traumatic brain injury: a randomized controlled trial. Crit Care 2008, 12:R61.
44. Cekic M., Johnson S.J., Bhatt V.H., Stein D.G. Progesterone treatment alters neurotrophin/proneurotrophin balance and receptor expression in rats with traumatic brain injury. Restor Neurol Neurosci 2012, 30:115-126.
45. Jodhka P.K., Kaur P., Underwood W., Lydon J.P., Singh M. The differences in neuro- protective efficacy of progesterone and medroxyprogesterone acetate correlate with their effects on brain-derived neurotrophic factor expression. Endocrinology 2009, 150:3162-3168.
46. Cutler S.M., Cekic M., Miller D.M., Wali B., VanLandingham J.W., Stein D.G. Progesterone improves acute recovery after traumatic brain injury in the aged rat. J Neurotrauma 2007, 24:1475-1486.
47. Yawno T., Hirst J.J., Castillo-Melendez M., Walker D.W. Role of neurosteroids in regulating cell death and proliferation in the late gestation fetal brain. Neuroscience 2009, 163(3):838-847.
48. Theoharides T.C., Zhang B. Neuro-inflammation, blood-brain barrier, seizures and autism. J Neuroinflammation 2011, 8:168-177.
49. Ishrat T., Sayeed I., Atif F., Hua F., Stein D.G. Progesterone and allopregnanolone attenuate blood-brain barrier dysfunction following permanent focal ischemia by regulating the expression of matrix metalloproteinases. Exp Neurol 2010, 226(1):183-190.
50. Minshew N.J., Keller T.A. The nature of brain dysfunction in autism: functional brain imaging studies. Curr Opin Neurol 2010, 23(2):124-130.
51. Sanchez A.M., Flamini M.I., Polak K., Palla G., Spina S., Mannella P., et al. Actin cytoskeleton remodelling by sex steroids in neurones. J Neuroendocrinol 2011, 24:195-201.
52. Jahagirdar V., Wagner C.K. Ontogeny of progesterone receptor expression in the subplate of fetal and neonatal rat cortex. Cereb Cortex 2010, 20(5):1046-1052.
53. Willing J, Wagner CK. Sensorimotor development in neonatal progesterone receptor knockout mice. Dev Neurobiol 2013 [Epub ahead of print].
54. Brun C.C., Nicolson R., Leporé N. Mapping brain abnormalities in boys with autism. Hum Brain Mapp 2009, 30(12):3887-3900.
55. Zikopoulos B., Barbas H. Changes in prefrontal axons may disrupt the network in autism. J Neurosci 2010, 30(44):14595-14609.
56. Carmody D.P., Lewis M. Regional white matter development in children with autism spectrum disorders. Dev Psychobiol 2010, 52(8):755-763.
57. Shukla D.K., Keehn B., Müller R.A. Tract-specific analyses of diffusion tensor imaging show widespread white matter compromise in autism spectrum disorder. J Child Psychol Psychiatry 2011, 52(3):286-295.
58. Steinman G. Predicting autism at birth. Med Hypotheses 2013, 81(1):21-25.
59. Baulieu E., Schumacher M. Progesterone as a neuroactive neurosteroid, with special reference to the effect of progesterone on myelination. Steroids 2000, 65:605-612.
60. Garcia-Segura L.M., Melcangi R.C. Steroids and glial cell function. Glia 2006, 54(6):485-498.
61. Wagner C.K., Nakayama A.Y., De Vries G.J. Potential role of maternal progesterone in the sexual differentiation of the brain. Endocrinology 1998, 139(8):3658-3661.
62. Gil M., Bhatt R., Picotte K.B., Hull E.M. Sexual experience increases oxytocin receptor gene expression and protein in the medial preoptic area of the male rat. Psychoneuroendocrinology 2013, 38(9):1688-1697.
63. Breton A.B., Austin K.J., Leedy M.G., Alexander B.M. Effects of progesterone and RU486 on the development and expression of adult male sexual behaviour and gene expression in the amygdala and preoptic area of the hypothalamus. Reprod Fertil Dev 2012, 24(7):916-922.
64. Barha C.K., Ishrat T., Epp J.R., Galea L.A., Stein D.G. Progesterone treatment normalizes the levels of cell proliferation and cell death in the dentate gyrus of the hippocampus after traumatic brain injury. Exp Neurol 2011, 231(1):72-81.
65. Woolley C.S., McEwen B.S. Roles of estradiol and progesterone in regulation of hippocampal dendritic spine density during the estrous cycle in the rat. J Comp Neurol 1993, 336:293-306.
66. McEwen B.S., Woolley C.S. Estradiol and progesterone regulate neuronal structure and synaptic connectivity in adult as well as developing brain. Exp Gerontol 1994, 29(3-4):431-436.
67. Sakamoto H., Ukena K., Tsutsui K. Effects of progesterone synthesized de novo in the developing Purkinje cell on its dendritic growth and synaptogenesis. J Neurosci 2001, 21:6221-6232.
68. Romeo R.D., Waters E.M., McEwen B.S. Steroid-induced hippocampal synaptic plasticity: sex differences and similarities. Neuron Glia Biol 2004, 1(3):219-229.
69. Sá S.I., Lukoyanova E., Madeira M.D. Effects of estrogens and progesterone on the synaptic organization of the hypothalamic ventromedial nucleus. Neuroscience 2009, 162(2):307-316.
70. Baudry M., Bi X., Aguirre C. Progesterone-estrogen interactions in synaptic plasticity and neuroprotection. Neuroscience 2013, 239:280-294.
71. Wegiel J., Kuchna I., Nowicki K., et al. The neuropathology of autism: defects of neurogenesis and neuronal migration, and dysplastic changes. Acta Neuropathol 2010, 119(6):755-770.
72. Chugani D.C. Serotonin in autism and pediatric epilepsies. Ment Retard Dev Disabil Res Rev 2004, 10(2):112-116.
73. Azmitia E.C., Singh J.S., Whitaker-Azmitia P.M. Increased serotonin axons (immunoreactive to 5-HT transporter) in postmortem brains from young autism donors. Neuropharmacology 2011, 60(7-8):1347-1354.
74. Lima F.B., Bethea C.L. Ovarian steroids decrease DNA fragmentation in the serotonin neurons of non-injured rhesus macaques. Mol Psychiatry 2010, 15(6):657-668.
75. Bethea C.L., Smith A.W., Centeno M.L., Reddy A.P. Long-term ovariectomy decreases serotonin neuron number and gene expression in free ranging macaques. Neuroscience 2011, 192:675-688.
76. Rivera H.M., Bethea C.L. Ovarian steroids increase PSD-95 expression and dendritic spines in the dorsal raphe of ovariectomized macaques. Synapse 2013, 67(12):897-908.
77. Lauder J.M. Ontogeny of the serotonergic system in the rat: serotonin as a developmental signal. Ann N Y Acad Sci 1990, 600:297-313.
78. Mazer C., Muneyyirci J., Taheny K., Raio N., Borella A., Whitaker-Azmitia P.M. Serotonin depletion during synaptogenesis leads to decreased synaptic density and learning deficits in the adult rat: a possible model of neurodevelopmental disorders with cognitive deficits. Brain Res 1997, 760(1-2):68-73.
79. Whitaker-Azmitia P.M., Druse M., Walker P., Lauder J.M. Serotonin as a developmental signal. Behav Brain Res 1996, 73(1-2):19-29.
80. Wagner C.K. Progesterone receptors and neural development: a gap between bench and bedside?. Endocrinology 2008, 149:2743-2749.
81. Mueller B.R., Bale T.L. Sex-specific programming of offspring emotionality after stress early in pregnancy. J Neurosci 2008, 28:9055-9065.
82. Ellison P.T. Human ovarian function and reproductive ecology: new hypotheses. Am Anthropol 1990, 92:933-952.
83. Kalantaridou S.N., Makrigiannakis A., Zoumakis E., Chrousos G.P. Stress and the female reproductive system. J Reprod Immunol 2004, 62(1-2):61-68.
84. Hall N.R. What agent should be used to prevent recurrent preterm birth: 17-P or natural progesterone?. Obstet Gynecol Clin North Am 2011, 38(2):235-246.
85. Halpert J. Altering the primal environment: health effects associated with assisted reproductive technologies. Environ Health Perspect 2012, 120(10):a390-a395.
86. Hajszan T., Leranth C. Bisphenol A interferes with synaptic remodeling. Front Neuroendocrinol 2010, 31(4):519-530.
87. Wolff M.S., Teitelbaum S.L., Windham G., et al. Pilot study of urinary biomarkers of phytoestrogens, phthalates, and phenols in girls. Environ Health Perspect 2007, 115(1):116-121.
88. Matsunaga H., Mizota K., Uchida H., Uchida T., Ueda H. Endocrine disrupting chemicals bind to a novel receptor, microtubule-associated protein 2, and positively and negatively regulate dendritic outgrowth in hippocampal neurons. J Neurochem 2010, 114(5):1333-1343.
89. Desoto M.C., Hitlan R.T. Sorting out the spinning of autism: heavy metals and the question of incidence. Acta Neurobiol Exp (Wars) 2010, 70(2):165-176.
90. Rivera R., Yacobson I., Grimes D. The mechanism of action of hormonal contraceptives and intrauterine devices. Am J Obstet Gynecol 1999, 181:1263-1269.
91. Ingudomnukul E., Baron-Cohen S., Wheelwright S., Knickmeyer R. Elevated rates of testosterone-related disorders in women with autism spectrum conditions. Horm Behav 2007, 51(5):597-604.
92. Carmichael S.L., Shaw G.M., Laurent C., Croughan M.S., Olney R.S., Lammer E.J. Maternal progestin intake and risk of hypospadias JAMA. Pediatrics 2005, 159(10):957-962.
93. Hvidtjørn D., Schieve L., Schendel D., Jacobsson B., Svaerke C., Thorsen P. Cerebral palsy, autism spectrum disorders, and developmental delay in children born after assisted conception: a systematic review and meta-analysis. Arch Pediatr Adolesc Med 2009, 16:72-83.
94. Walker CK, Anderson KW, Milano KM et al. Trophoblast inclusions are significantly increased in the placentas of children in families at risk for autism. Biol Psychiatry 2013 [epub ahead of print].
95. Brunton P.J., Russell J.A. Endocrine induced changes in brain function during pregnancy. Brain Res 2010, 1364:198-215.
96. Mesiano S., Wang Y., Norwitz E.R. Progesterone receptors in the human pregnancy uterus: do they hold the key to birth timing?. Reprod Sci 2011, 18:6-19.
97. Lockwood C.J., Stocco C., Murk W., Kayisli U.A., Funai E.F., Schatz F. Human labor is associated with reduced decidual cell expression of progesterone, but not glucocorticoid, receptors. J Clin Endocrinol Metab 2010, 95:2271-2275.
98. Hill M., Pařízek A., Jirásek R.J.E. Reduced progesterone metabolites in human late pregnancy. Physiol Res 2011, 60:225-241.
99. Shelton J.F., Tancredi D.J., Hertz-Picciotto I. Independent and dependent contributions of advanced maternal and paternal ages to autism risk. Autism Res 2010, 3:30-39.
100. Rai D., Lewis G., Lundberg M., et al. Parental socioeconomic status and risk of offspring autism spectrum disorders in a Swedish population-based study. J Am Acad Child Adolesc Psychiatry 2012, 51(5):467-476.
101. Cardwell M.S. Stress: pregnancy considerations. Obstet Gynecol Surv 2013, 18(2):119-129.
102. Su M.T., Lee I.W., Chen Y.C., Kuo P.L. Association of progesterone receptor polymorphism with idiopathic recurrent pregnancy loss in Taiwanese Han population. J Assist Reprod Genet 2011, 28(3):239-243.