Abstract
Hormonal imprinting takes place at the first encounter between the developing receptor and its target hormone and the encounter determines the receptor's binding capacity for life. In the critical period of development, when the window for imprinting is open, the receptor can be misdirected by related hormones, synthetic hormones, and industrial or communal endocrine disruptors which cause faulty hormonal imprinting with life-long consequences. Considering these facts, the hormonal imprinting is a functional teratogen provoking alterations in the perinatal (early postnatal) period. One single encounter with a low dose of the imprinter in the critical developmental period is enough for the formation of faulty imprinting, which is manifested later, in adult age. This has been justified in the immune system, in sexuality, in animal behavior and brain neurotransmitters etc. by animal experiments and human observations. This review points to the faulty hormonal imprinting in the case of bones (skeleton), by single or repeated treatments. The imprinting is an epigenetic alteration which is inherited to the progeny generations. From clinical aspect, the faulty imprinting can have a role in the pathological development of the bones as well, as in the risk of osteoporotic fractures, etc.
Keywords: Hormonal imprinting, synthetic hormones, bone manifestation, animal experiments, human observations, fractures.
Graphical Abstract
[1]
Csaba G. Phylogeny and ontogeny of hormone receptors: The selection theory of receptor formation and hormonal imprinting. Biol Rev Camb Philos Soc 1980; 55: 47-63.
[2]
Csaba G. Hormonal imprinting: Its role during the evolution and development of hormones and receptors. Cell Biol Int 2000; 24: 407-14.
[3]
Csaba G. Hormonal imprinting: Phylogeny, ontogeny, diseases and possible role in present-day human evolution. Cell Biochem Funct 2008; 26: 1-10.
[4]
Csaba G. The biological basis and clinical significance of hormonal imprinting, an epigenetic process. Clin Epigenetics 2011; 2: 187-96.
[5]
Tchernitchin A, Tchernitchin NN, Mena MA, Javy Soto J. Imprinting: Perinatal exposures cause the development of diseases during the adult age. Acta Biol Hung 1999; 50: 425-40.
[7]
Hashemi F, Tekes K, Laufer R, Tóthfalusi L, Csaba G. Effect of a single neonatal oxytocin treatment hormonal imprinting) on the biogenic amine level of the adult rat brain: Could oxytocin-induced labor cause pervasive developmental diseases? Reprod Sci 2011; 20: 1255-63.
[8]
Kőhidai L, Lajkó E, Pállinger É, Csaba G. Verification of epigenetic inheraitance in a unicellular model system: Multigenerational effects of hormonal imprinting. Cell Biol Int 2012; 36: 951-9.
[9]
Karabélyos C, Horváth C, Holló I, Csaba G. Effect of perinatal synthetic steroid hormone (allylestrenol, diethylstilbestrol) treatment (hormonal imprinting) on the bone mineralization of the adult male and female rat. Life Sci 1999; 64: 105-10.
[10]
Karabélyos C, Horváth C, Holló I, Csaba G. Effect of neonatal glucocorticoid treatment on bone mineralization of adult nontreated, dexamethasone-treated or vitamin D3-treated rats. Gen Phrmacol 1998; 31: 789-91.
[11]
Karabélyos C, Horváth C, Holló I, Csaba G. Effect of single neonatal vitamin D3 treatment (hormonal imprinting) on the bone mineralization of adult non-treated and dexamethasone-treated rats. Hum Exp Toxicol 1998; 17: 424-9.
[12]
Csaba G, Inczefi-Gonda Á. Effect of vitamin D3 treatment in the neonatal or adolescent age (hormonal imprinting) on the thymic glucocorticoid receptor of the adult male rat. Horm Res 1999; 51: 280-3.
[13]
Jansson JO, Ekberg S, Isakson O, Mode A, Gustafsson JA. Imprinting of growth hormone secretion, body growth, and hepatic steroid metabolism, by neonatal testosterone. Endocrinology 1985; 117: 1881-90.
[14]
Sims NA, Brennan K, Spaliviero J, Handelsman DJ, Seibel MJ. Perinatal testosterone surge is required for normal adult bone size but not for normal bone remodeling. Am J Physiol Endocrinol Metab 2006; 290: E456-2.
[15]
Connelly KJ, Larson EA, Marks DL, Klein RF. Neonatal estrogen exposure results in biphasic age-depend ent effects on the sexual development of male mice. Endocrinology 2015; 156: 193-202.
[16]
Fukuzawa Y, Nobata S, Katoh M, et al. Effect of neonatal exposure to diethylstilbestrol and tamoxifen on pelvis and femur in male mice. Anat Rec 1996; 244: 416-22.
[17]
Sliwa E, Dobrowolswki P, Piersiak T. Bone development of suckling piglets after prenatal, neonatal or perinatal treatment with dexamethasone. J Anim Physiol Anim Nutr 2010; 94: 293-306.
[18]
Migliaccio S, Newbold RR, Bullock BC, et al. Alterations of maternal estrogen levels during gestation affect the skeleton of female offspring. Endocrinology 1996; 137: 2118-25.
[19]
Migliaccio S, Newbold RR, Teti A, et al. Transient estrogen exposure of female mice during early development permanently affects osteoclastogenesis in adulthood. Bone 2000; 27: 47-52.
[20]
Migliaccio S, Newbold RR, Bullock BC, McLachlan JA, Korach KS. Developmental exposure to estrogens induces persistent changes in skeletal tissue. Endocrinology 1992; 130: 1756-8.
[21]
Sims NA, Brennan K, Spaliviero J, Seibel MJ. Perinatal testosterone surge is required for normal adult bone size but not for normal bone remodeling. AJP Endocrinol Metab 2006; 290: E456-62.
[22]
Zhang Y, Wray AE, Ross AC. Perinatal exposure to vitamin A differentially regulates chondrocyte growth an the expression of aggrecan and matrix metalloprotein genes in the femur of neonatal rats. J Nutr 2012; 142: 649-54.
[23]
Devlin MJ, Bouxsein ML. Influence of pre-and peri-natal nutrition on skeletal acquisition and maintenance. Bone 2012; 50: 444-51.
[24]
Devlin MJ, Grasemann C, Cloutier AM, et al. Maternal perinatal diet induces developmental programming of bone architecture. J Endocrinol 2013; 217: 69-81.
[25]
Mardon J, Mathey J, Kati-Koulibaly S, et al. Influence of lifelong soy isoflavones consumption on bone mass in the rat. Exp Biol Med 2008; 233: 229-37.
[26]
Miettinen HM, Pulkkinen P, Jamsa T, et al. Effects of in utero and lactational TCDD exposure on bone development in differentially sensitive rat lines. Toxicol Sci 2005; 85: 1003-12.
[27]
Lundberg R, Lyche JL, Ropstad E, et al. Perinatal exposure to PCB 153, but not PCB 126, alters bone tissue composition in female goat offspring. Toxicology 2006; 228: 33-40.
[28]
Hermsen SA, Larsson S, Arima A, et al. In utero and lactational exposure to 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD) affects bone tissue in rhesus monkeys. Toxicology 2008; 253: 147-52.
[29]
Lejonklou MH, Christiansen S, Örberg J, et al. Low dose developmental exposure to bisphenol A alters the femoral bone geometry in wistar rats. Chemosphere 2016; 164: 339-46.
[30]
Fagnant HS, Usumcu M, Buckendahl P, Dunn MG, Shupper P, Shapses SA. Fetal and neonatal exposure to the endocrine disruptor, methoxychlor, reduces lean body mass and bone mineral density and increase cortical porosity. Calcif Tissue Int 2014; 95: 521-9.
[31]
Dancause KN, Cao X, Veru F, et al. Brief communication: Prenatal and early postnatal stress exposure influences long bone length in adult rat offspring. Am J Physiol Anthropol 2012; 149: 307-11.
[32]
Csaba G. The faulty perinatal hormonal imprinting as functional teratogen. Curr Pediatr Res 2016; 12: 222-9.
[33]
Csaba G. The present and future of human sexuality: Impact of faulty perinatal hormonal imprinting. Sex Med Rev 2017; 5: 163-9.
[34]
DeOliveira DH, Fighera TM, Bianchet LC, Kulak CA, Kulak J. Androgens and bone. Minerva Endocrinol 2012; 37: 305-14.
[35]
Krum SA. Direct transcriptional targets of sex steroid hormones in bone. J Cell Biochem 2011; 112: 401-8.
[36]
Lindberg MK, Vanderput L, Moverare Skrtic S, et al. Androgens and the skeleton. Minerva Endocrinol 2005; 30: 15-25.
[37]
Nicks KM, Fowler TW, Gaddy D. Reproductive hormones and bone. Curr Osteoporos Rep 2010; 8: 60-7.
[38]
Imai Y, Kondoh S, Kouzmenko A, Kato S. Regulation of bone metabolism by nuclear receptors. Mol Cell Endocrinol 2009; 310: 3-10.
[39]
Csaba G. Immunoendocrinology: Faulty hormonal imprinting in the immune system. Acta Microbiol Immunol Hung 2014; 61: 89-106.
[40]
Zallone A. Direct and indirect estrogen actions on osteoblasts and osteoclasts. Ann N Y Acad Sci 2006; 1068: 173-9.
[41]
Vidal O, Lindberg MK, Hollberg K, et al. Estrogen receptor specificity in the regulation of skeletal growth and maturation in male mice. Proc Natl Acad Sci USA 2000; 97: 5474-9.
[42]
Venken K, De Gendt K, Boonen S, et al. Relative impact of androgen and estrogen receptor activation in the effects of androgens on trabecular and cortical bone in growing male mice: A study in the androgen receptor knockout mouse model. J Bone Miner Res 2006; 21: 576-85.
[43]
Callewaert F, Sinnesal M, Gielen E, Boonen S, Vanderschueren D. Skeletal sexual dimorphism: relative contributon of sex steroids, GH-IGF1, and mechanical loading. J Endocrinol 2010; 207: 127-34.
[44]
De Coster S, van Larebeke N. Endocrine disrupting chemicals: Associated disorders and mechanisms of action. J Environ Public Health 2012; 713696.
[45]
Diamanti. Kandarakis E, Bourguignon JP, et al. Endocrine disrupting chemicals: An Endocrine Society scientific statement. Endocr Rev 2009; 30: 293-342.
[46]
Kundakovic M, Champagne FA. Epigenetic perspective on the developmental effects of bisphenol A. Brain Behav Immun 2011; 25: 1084-93.
[47]
Goudochnikov VI. Role of hormones in perinatal and early postnatal development: Possible contribution to programming/imprinting phenomena. Rus J Dev Biol 2015; 46: 237-45.
[48]
Newbold RR. Developmental exposure to endocrine-disrupting chemicals programs for reproductive tract alterations and obesity later in life. Am J Clin Nutr 2011; 94: 1939S-42S.
[49]
Godfrey KM, Costello PM, Lillycrop KA. Development, epigenetics and metabolic programming. Nestle Nutr Inst Workshop Ser 2016; 85: 71-80.
[50]
Csaba G, Kovács P. Impact of 5-azacytidine on insulin binding and insulin-induced receptor formation in Tetrahymena. Biochem Biophys Res Commun 1990; 168: 709-13.
[53]
Vaiserman A. Early-life exposure to endocrine disrupting chemicals and later-life health outcomes: An epigenetic bridge? Aging Dis 2014; 6: 419-29.
[54]
Bernal AJ, Jirtle RL. Epigenomic disruption: The effects of early developmental exposures. Birth Defects Res A Clin Mol Teratol 2010; 88: 938-44.
[56]
Plagemann A. Perinatal programming and functional teratogenesis: Impact on body weight regulation and obesity. Physiol Behav 2005; 86: 661668.
[57]
Clowes JA, Riggs BL, Khosla S. The role of immune system in the pathophysiology of osteoporosis. Immunol Rev 2005; 208: 207-27.
[58]
Yhou X, Dai X, Wu X, et al. Overexpression of Bmi1 in lymphocytes stimulates skeletogenesis by improving the osteogenetic microenvironment. Sci Rep 2016; 6: 29171.
[59]
Yin J, Dwyer T, Riley M, Cochrane J, Jones G. The association between maternal diet during pregnancy and bone mass of the children at age 16. Eur J Clin Nutr 2010; 64: 131-7.
[60]
Chen JR, Lazarenko OP, Blackburn MR, Shankar K. Dietary factors during early life program bone formation in female rats. FASEB J 2017; 31: 376-87.
[61]
Becker LA, Kunkel AJ, Brown MR, Ball EE, Williams MT. Effects of dietary phytoestrogen exposure during perinatal period. Neurotoxicol Teratol 2005; 27: 825-34.
[62]
Wisniewski AB, Cernetich A, Gearhart JP, Klein SL. Perinatal exposure to genistein alters reproductive development and aggressive behavior in male mice. Physiol Behav 2005; 84: 327-34.
[63]
Koletzko B. Early nutrition and its later consequences: new opportunities. Adv Exp Med Biol 2005; 569: 1-12.
[64]
Rubin BS, Murray MK, Damassa DA, King JC, Soto AM. Perinatal exposure to low doses of bisphenol A affects body weight, patterns of estrus cyclicity, and plasma LH levels. Environ Health Perspect 2001; 109: 675-80.
[65]
Barouki R, Gluckman PD, Grandjean P, Hanson M, Heindel JJ. (2012) Developmental origins of non-communicable disease: Implication for research and public health. Environ Health 2012; 11: 42.
[66]
Merchant Research and consulting. Bisphenol S (BPA) 2014 world market outlook anf forecast up to 2018. Market Publishers 2014 January, page 165..
[67]
Dörner G. Environment-and gene-dependent human ontogenesis, sociogenesis and phylogenesis (eco-geno-onto-socio-phylogenesis). Neuroendocrinol Lett 2004; 25: 164-8.
[68]
Cooper C, Westlake S, Harwey N, Javaid K, Dennison E, Hanson M. Review: Developmental origins of osteoporotic fracture. Osteoporos Int 2006; 17: 337-47.
[69]
Feinberg AP. Phenotypic plasticity and the epigenetics of human disease. Nature 2007; 447: 433-40.
[70]
Csaba G, Kovács P, Pállinger É. Transgenerational effect of neonatal vitamin A or D treatment (hormonal imprinting) on the hormone content of rat immune cells. Horm Metab Res 2007; 39: 197-201.
[71]
Tekes K, Gyenge M, Hantos M, Csaba G. Transgenerational hormonal imprinting caused by vitamin A and vitamin D treatment of newborn rats. Alterations in the biogenic amine contents of the adult brain. Brain Dev 2009; 31: 666-70.
[72]
Csaba G. Transgenerational effects of perinatal hormonal imprinting. In: Tollefsbol T, Ed. Transgenerational epigenetics Elsevier
New York.
[73]
Xue J, Schoenrock SA, Valdar W, Tarantino LM, Ideraabdullah FY. Maternal vitamin D depletion alters DNA methylation at imprinted loci in multiple generations. Clin Epigenetics 2016; 8: 107.
[74]
Csaba G. Faulty perinatal hormonal imprinting caused by exogeneous vitamin D - dangers and problems. Austin J Nutr Food Sci 2016; 4: 1-5.
[75]
Attina TM, Hauser R, Sathyanarayana S, et al. Trasande L.s exposure to endocrine disrupting chemicals in the USA: A population-based burden and cost analysis. Lancet Diabetes Endocrinol 2016; 4: 996-1003.
Related Journals
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry
Current Diabetes Reviews
Current Neurovascular Research
Current Respiratory Medicine Reviews
Infectious Disorders - Drug Targets
Endocrine, Metabolic & Immune Disorders - Drug Targets
Current Stem Cell Research & Therapy
Current Alzheimer Research
Current HIV Research
Current Aging Science
Related Books
Textbook of Advanced Dermatology: Pearls for Academia and Skin Clinics (Part 1)
The NLRP3 Inflammasome: An Attentive Arbiter of Inflammatory Response
Morphea and Related Disorders
Frontiers in Clinical Drug Research - CNS and Neurological Disorders
Stem Cells in Clinical Application and Productization
Marine Biopharmaceuticals: Scope and Prospects
Frontiers in Clinical Drug Research - Anti-Cancer Agents
Handbook of Laparoscopy Instruments
Optical Coherence Tomography Angiography for Choroidal and Vitreoretinal Disorders – Part 2
Female Arousal and Orgasm: Anatomy, Physiology, Behaviour and Evolution
Article Metrics
118
12
1
