Reproductive technologies and Parkinson’s disease: experimental study of substantia nigra in the brain and motor functions on C57BL/6 and B6.CG-TG mice

Мұқаба

Дәйексөз келтіру

Толық мәтін

Ашық рұқсат Ашық рұқсат
Рұқсат жабық Рұқсат берілді
Рұқсат жабық Тек жазылушылар үшін

Аннотация

Parkinson’s disease (PD) is an age-related neurodegenerative pathology characterized by abnormalities of the brain's dopaminergic system, alpha-synucleinopathy and motor dysfunction. Possible association of assisted reproductive technologies (ARTs) with neuropathologies is discussed in medicine literature, but there is a lack of experimental studies addressing this issue. The current study investigates the effects of ARTs, i.e. in vitro culture of preimplantation embryos and embryo transfer (ET) on the features characteristic for PD in offspring: motor dysfunction, decrease of neuronal density, e.g. density of dopaminergic neurons, as well as alpha-synuclein accumulation in substantia nigra pars compacta (SNpc). Male offspring of the B6.Cg-Tg strain and C57BL/6 strain (hereinafter referred as wild type, WT) obtained by ART (groups B6.Cg-Tg ET and WT ET) or by natural mating (groups B6.Cg-Tg CTL and WT CTL) were tested at the age of six months. Motor coordination and body balance were studied using the rotarod test; the density of neurons, as well as the accumulation of alpha-synuclein in the SNpc were assessed by immunohistochemical method. It was shown that B6.Cg-Tg mice obtained without ART (B6.Cg-Tg CTL) are characterized by the low density of neurons, including dopaminergic ones, as well as the accumulation of alpha-synuclein in SNpc as compared to wild type mice (WT CTL). Wild-type offspring obtained by ART (WT ET group) were characterized by the impairment in motor coordination and body balance, as well as by the decrease in the density of neurons in the SNpc, including dopaminergic ones. Offspring of the B6.Cg-Tg strain obtained by ART (B6.Cg-Tg ET group) were characterized by an increased accumulation of alpha-synuclein in the SNpc. The results of our study indicate possible association between using of modern reproductive technologies and predisposition to the neurodegenerative process and manifestations of the features characteristic to PD phenotype in offspring.

Толық мәтін

Рұқсат жабық

Авторлар туралы

V. Kozeneva

Institute of Cytology and Genetics Siberian Branch of the Russian Academy of Sciences; Novosibirsk State University

Email: amstis@yandex.ru
Ресей, Novosibirsk; Novosibirsk

I. Rozhkova

Institute of Cytology and Genetics Siberian Branch of the Russian Academy of Sciences

Email: amstis@yandex.ru
Ресей, Novosibirsk

E. Brusentsev

Institute of Cytology and Genetics Siberian Branch of the Russian Academy of Sciences

Email: amstis@yandex.ru
Ресей, Novosibirsk

T. Rakhmanova

Institute of Cytology and Genetics Siberian Branch of the Russian Academy of Sciences; Novosibirsk State University

Email: amstis@yandex.ru
Ресей, Novosibirsk; Novosibirsk

N. Shavshaeva

Institute of Cytology and Genetics Siberian Branch of the Russian Academy of Sciences; Novosibirsk State University

Email: amstis@yandex.ru
Ресей, Novosibirsk; Novosibirsk

S. Afanasova

Institute of Cytology and Genetics Siberian Branch of the Russian Academy of Sciences; Novosibirsk State University

Email: amstis@yandex.ru
Ресей, Novosibirsk; Novosibirsk

D. Lebedeva

Institute of Cytology and Genetics Siberian Branch of the Russian Academy of Sciences

Email: amstis@yandex.ru
Ресей, Novosibirsk

S. Okotrub

Institute of Cytology and Genetics Siberian Branch of the Russian Academy of Sciences

Email: amstis@yandex.ru
Ресей, Novosibirsk

T. Igonina

Institute of Cytology and Genetics Siberian Branch of the Russian Academy of Sciences

Email: amstis@yandex.ru
Ресей, Novosibirsk

S. Amstislavskya

Institute of Cytology and Genetics Siberian Branch of the Russian Academy of Sciences

Хат алмасуға жауапты Автор.
Email: amstis@yandex.ru
Ресей, Novosibirsk

Әдебиет тізімі

  1. Barker DJ (2007) The origins of the developmental origins theory. J Intern Med 261: 412–417. https://doi.org/10.1111/j.1365-2796.2007.01809.x
  2. Motrenko T (2010) Embryo-fetal origin of diseases – new approach on epigenetic reprogramming. Arch Perinat Med 6.
  3. Huang HF, Sheng J-Z (2014) Gamete and embryo-fetal origins of adult diseases. Dordrecht: Springer. https://doi.org/10.1007/978-94-007-7772-9
  4. Margolis ET, Gabard-Durnam LJ (2024) Prenatal influences on postnatal neuroplasticity: Integrating DOHaD and sensitive/critical period frameworks to understand biological embedding in early development. Infancy. https://doi.org/10.1111/infa.12588
  5. Pinborg A, Loft A, Ziebe S, Nyboe Andersen A (2004) What is the most relevant standard of success in assisted reproduction? Is there a single 'parameter of excellence'? Hum Reprod 19: 1052–1054. https://doi.org/10.1093/humrep/deh228
  6. Sandin S, Nygren KG, Iliadou A, Hultman CM, Reichenberg A (2013) Autism and mental retardation among offspring born after in vitro fertilization. JAMA 310: 75–84. https://doi.org/10.1001/jama.2013.7222
  7. Liu L, Gao J, He X, Cai Y, Wang L, Fan X (2017) Association between assisted reproductive technology and the risk of autism spectrum disorders in the offspring: a meta-analysis. Sci Rep 7: 46207. https://doi.org/10.1038/srep46207
  8. Berntsen S, Soderstrom-Anttila V, Wennerholm UB, Laivuori H, Loft A, Oldereid NB, Romundstad LB, Bergh C, Pinborg A (2019) The health of children conceived by ART: 'the chicken or the egg?' Hum Reprod Update 25: 137–158. https://doi.org/10.1093/humupd/dmz001
  9. Andreadou MT, Katsaras GN, Talimtzi P, Doxani C, Zintzaras E, Stefanidis I (2021) Association of assisted reproductive technology with autism spectrum disorder in the offspring: an updated systematic review and meta-analysis. Eur J Pediatr 180: 2741–2755. https://doi.org/10.1007/s00431-021-04187-9
  10. Ono M, Kuji N, Ueno K, Kojima J, Nishi H (2024) The long-term outcome of children conceived through assisted reproductive technology. Reprod Sci 31: 583–590. https://doi.org/10.1007/s43032-023-01339-0
  11. Sonigo C, Ahdad-Yata N, Pirtea P, Solignac C, Grynberg M, Sermondade N (2024) Do IVF culture conditions have an impact on neonatal outcomes? A systematic review and meta-analysis. J Assist Reprod Genet 41: 563–580. https://doi.org/10.1007/s10815-024-03020-0
  12. Zhang S, Luo Q, Meng R, Yan J, Wu Y, Huang H (2024) Long-term health risk of offspring born from assisted reproductive technologies. J Assist Reprod Genet 41: 527–550. https://doi.org/10.1007/s10815-023-02988-5
  13. Ramos-Ibeas P, Heras S, Gomez-Redondo I, Planells B, Fernandez-Gonzalez R, Pericuesta E, Laguna-Barraza R, Perez-Cerezales S, Gutierrez-Adan A (2019) Embryo responses to stress induced by assisted reproductive technologies. Mol Reprod Dev 86: 1292–1306. https://doi.org/10.1002/mrd.23119
  14. Balayla J, Sheehy O, Fraser WD, Seguin JR, Trasler J, Monnier P, MacLeod AA, Simard MN, Muckle G, Berard A (2017) 3D-study research group from the integrated research network in perinatology of Quebec and Eastern Ontario. Neurodevelopmental outcomes after assisted reproductive technologies. Obstet Gynecol 129: 265–272. https://doi.org/10.1097/AOG.0000000000001837
  15. Sacha CR, Gopal D, Liu CL, Cabral HR, Stern JE, Carusi DA, Racowsky C, Bormann CL (2022) The impact of single-step and sequential embryo culture systems on obstetric and perinatal outcomes in singleton pregnancies: the Massachusetts Outcomes Study of Assisted Reproductive Technology. Fertil Steril 117: 1246–1254. https://doi.org/10.1016/j.fertnstert.2022.03.005
  16. Husen SC, Koning IV, Go ATJI, Groenenberg IAL, Willemsen SP, Rousian M, Steegers-Theunissen RPM (2021) IVF with or without ICSI and the impact on human embryonic brain development: the Rotterdam Periconceptional Cohort. Hum Reprod 36: 596–604. https://doi.org/10.1093/humrep/deaa341
  17. Sunde A (2019) Embryo culture and phenotype of the offspring. In Vitro Fertilization: 877–889. https://doi.org/10.1007/978-3-319-43011-9_74
  18. Ecker DJ, Stein P, Xu Z, Williams CJ, Kopf GS, Bilker WB, Abel T, Schultz RM (2004) Long-term effects of culture of preimplantation mouse embryos on behavior. Proc Natl Acad Sci U S A 101: 1595–1600. https://doi.org/10.1073/pnas.0306846101
  19. Rose C, Rohl FW, Schwegler H, Hanke J, Yilmazer-Hanke DM (2006) Maternal and genetic effects on anxiety-related behavior of C3H/HeN, DBA/2J and NMRI mice in a motility-box following blastocyst transfer. Behav Genet 36: 745–762. https://doi.org/10.1007/s10519-005-9037-4
  20. Lopez-Cardona AP, Fernandez-Gonzalez R, Perez-Crespo M, Alen F, de Fonseca FR, Orio L, Gutierrez-Adan A (2015) Effects of synchronous and asynchronous embryo transfer on postnatal development, adult health, and behavior in mice. Biol Reprod 93: 85. https://doi.org/10.1095/biolreprod.115.130385
  21. Hu M, Lou Y, Liu S, Mao Y, Le F, Wang L, Li L, Wang Q, Li H, Lou H, Wang N, Jin F (2020) Altered expression of DNA damage repair genes in the brain tissue of mice conceived by in vitro fertilization. Mol Hum Reprod 26: 141–153. https://doi.org/10.1093/molehr/gaaa010
  22. Zhu W, Zheng J, Wen Y, Li Y, Zhou C, Wang Z (2020) Effect of embryo vitrification on the expression of brain tissue proteins in mouse offspring. Gynecol Endocrinol 36: 973–977. https://doi.org/10.1080/09513590.2020.1734785
  23. Qin NX, Zhao YR, Shi WH, Zhou ZY, Zou KX, Yu CJ, Liu X, Dong ZH, Mao YT, Zhou CL, Yu JL, Liu XM, Sheng JZ, Ding GL, Zhao WL, Wu YT, Huang HF (2021) Anxiety and depression-like behaviours are more frequent in aged male mice conceived by ART compared with natural conception. Reproduction 162: 437–448. https://doi.org/10.1530/REP-21-0175
  24. Брусенцев ЕЮ, Игонина ТН, Рожкова ИН, Окотруб СВ, Лебедева ДА, Владимирова ЕВ, Козенева ВС, Амстиславский СЯ (2023) Влияние культивирования in vitro и переноса эмбрионов на плотность нейронов и нейрогенез в головном мозге мышей линии С57BL/6J. Нейрохимия 40: 223–233. [Brusentsev EYu, Igonina TN, Rozhkova IN, Okotrub SV, Lebedeva DA, Vladimirova EV, Kozeneva VS, Amstislavsky SYa (2023) The effect of in vitro culture and embryo transfer on neuronal density and neurogenesis in the brains of C57BL/6J mice. Neurochem J 17: 349–358. (In Russ)]. https://doi.org/10.31857/S1027813323030068
  25. Rose C, Schwegler H, Hanke J, Rohl FW, Yilmazer-Hanke DM (2006) Differential effects of embryo transfer and maternal factors on anxiety-related behavior and numbers of neuropeptide Y (NPY) and parvalbumin (PARV) containing neurons in the amygdala of inbred C3H/HeN and DBA/2J mice. Behav Brain Res 173: 163–168. https://doi.org/10.1016/j.bbr.2006.06.017
  26. Beitz JM (2014) Parkinson’s disease: a review. Front Biosci (Schol Ed) 6: 65–74. https://doi.org/10.2741/S415
  27. Tran J, Anastacio H, Bardy C (2020) Genetic predispositions of Parkinson’s disease revealed in patient-derived brain cells. NPJ Parkinson’s disease. 6: 8.
  28. Bidesi NS, Vang Andersen I, Windhorst AD, Shalgunov V, Herth MM (2021) The role of neuroimaging in Parkinson’s disease. J Neurochem 159: 660–689.
  29. Sellbach AN, Boyle RS, Silburn PA, Mellick GD (2006) Parkinson's disease and family history. Parkinsonism & Related Disorders 12(7): 399–409. https://doi.org/10.1016/j.parkreldis.2006.03.002
  30. Korchounov A, Meyer MF, Krasnianski M (2010) Postsynaptic nigrostriatal dopamine receptors and their role in movement regulation. J Neural Transm (Vienna) 117: 1359–1369. https://doi.org/10.1007/s00702-010-0454-z
  31. Hayes MT (2019) Parkinson’s disease and parkinsonism. Am J Med 132: 802–807. https://doi.org/10.1016/j.amjmed.2019.03.001
  32. Halliday GM, Del Tredici K, Braak H (2006) Critical appraisal of brain pathology staging related to presymptomatic and symptomatic cases of sporadic Parkinson’s disease. J Neural Transmis Supp 70: 99.
  33. Dickson DW, Braak H, Duda JE, Duyckaerts C, Gasser T, Halliday GM, Hardy J, Leverenz JB, Del Tredici K, Wszolek ZK, Litvan I (2009) Neuropathological assessment of Parkinson’s disease: refining the diagnostic criteria. Lancet Neurol 8: 1150–1157.
  34. Burre J, Sharma M, Sudhof TC (2018) Cell biology and pathophysiology of α-synuclein. Cold Spring Harb Perspect Med 8: a024091. https://doi.org/10.1101/cshperspect.a024091
  35. Polymeropoulos MH, Lavedan C, Leroy E, Ide SE, Dehejia A, Dutra A, Pike B, Root H, Rubenstein J, Boyer R, Stenroos ES, Chandrasekharappa S, Athanassiadou A, Papapetropoulos T, Johnson WG, Lazzarini AM, Duvoisin RC, Di Iorio G, Golbe LI, Nussbaum RL (1997) Mutation in the alpha-synuclein gene identified in families with Parkinson’s disease. Science 276: 2045–2047. https://doi.org/10.1126/science.276.5321.2045
  36. Spillantini MG, Schmidt ML, Lee VM, Trojanowski JQ, Jakes R, Goedert M (1997) Alpha-synuclein in Lewy bodies. Nature 388: 839–840. https://doi.org/10.1038/42166
  37. Lai TT, Kim YJ, Nguyen PT, Koh YH, Nguyen TT, Ma HI, Kim YE (2021) Temporal evolution of inflammation and neurodegeneration with alpha-synuclein propagation in Parkinson’s disease mouse model. Fron Int Neurosci 15: 715190.
  38. Poewe W, Seppi K, Tanner CM, Halliday GM, Brundin P, Volkmann J, Schrag AE, Lang AE (2017) Parkinson disease. Nat Rev Dis Primers 3: 17013. https://doi.org/10.1038/nrdp.2017.13
  39. Feuer SK, Rinaudo PF (2017) Physiological, metabolic and transcriptional postnatal phenotypes of in vitro fertilization (IVF) in the mouse. J Dev Origin Heal Dis 8: 403–410. https://doi.org/10.1017/s204017441700023x
  40. Dulioust E, Toyama K, Busnel MC, Moutier R, Carlier M, Marchaland C, Ducot B, Roubertoux P, Auroux M (1995) Long-term effects of embryo freezing in mice. Proc Natl Acad Sci U S A 92: 589–593. https://doi.org/10.1073/pnas.92.2.589
  41. Djuwantono T, Aviani JK, Permadi W, Achmad TH, Halim D (2020) Risk of neurodevelopmental disorders in children born from different ART treatments: a systematic review and meta-analysis. J Neurodev Disord 12: 33. https://doi.org/10.1186/s11689-020-09347-w https://www.jax.org/strain/006823
  42. Unger EL, Eve DJ, Perez XA, Reichenbach DK, Xu Y, Lee MK, Andrews AM (2006) Locomotor hyperactivity and alterations in dopamine neurotransmission are associated with overexpression of A53T mutant human alpha-synuclein in mice. Neurobiol Dis 21: 431–443. https://doi.org/10.1016/j.nbd.2005.08.005
  43. Pupyshev AB, Korolenko TA, Akopyan AA, Amstislavskaya TG, Tikhonova MA (2018) Suppression of autophagy in the brain of transgenic mice with overexpression of А53Т-mutant α-synuclein as an early event at synucleinopathy progression. Neurosci Lett 672: 140–144. https://doi.org/10.1016/j.neulet.2017.12.001
  44. Korolenko TA, Shintyapina AB, Belichenko VM, Pupyshev AB, Akopyan AA, Fedoseeva LA, Russkikh GS, Vavilin VA, Tenditnik MV, Lin C-L, Amstislavskaya TG, Tikhonova MA (2020) Early Parkinson’s disease-like pathology in a transgenic mouse model involves a decreased Cst3 mRNA expression but not neuroinflammatory response in the brain. Med Univer 3: 66–78.
  45. Seo JH, Kang SW, Kim K, Wi S, Lee JW, Cho SR (2020) Environmental enrichment attenuates oxidative stress and alters detoxifying enzymes in an A53T α-synuclein transgenic mouse model of Parkinson’s disease. Antioxidants (Basel) 9: 928. https://doi.org/10.3390/antiox9100928
  46. Zhang Y, Wu Q, Ren Y, Zhang Y, Feng L (2022) A53T α-synuclein induces neurogenesis impairment and cognitive dysfunction in line M83 transgenic mice and reduces the proliferation of embryonic neural stem cells. Brain Res Bull 182: 118–129. https://doi.org/10.1016/j.brainresbull.2022.02.010
  47. Graham DR, Sidhu A (2010) Mice expressing the A53T mutant form of human alpha-synuclein exhibit hyperactivity and reduced anxiety-like behavior. J Neurosci Res 88: 1777–1183. https://doi.org/10.1002/jnr.22331
  48. Tang H, Gao Y, Zhang Q, Nie K, Zhu R, Gao L, Feng S, Wang L, Zhao J, Huang Z, Zhang Y, Wang L (2017) Chronic cerebral hypoperfusion independently exacerbates cognitive impairment within the pathopoiesis of Parkinson’s disease via microvascular pathologys. Behav Brain Res 333: 286–294. https://doi.org/10.1016/j.bbr.2017.05.061
  49. Langley MR, Ghaisas S, Palanisamy BN, Ay M, Jin H, Anantharam V, Kanthasamy A, Kanthasamy AG (2021) Characterization of nonmotor behavioral impairments and their neurochemical mechanisms in the MitoPark mouse model of progressive neurodegeneration in Parkinson’s disease. Exp Neurol 341: 113716. https://doi.org/10.1016/j.expneurol.2021.113716
  50. Рожкова ИН, Окотруб СВ, Брусенцев ЕЮ, Рахманова ТА, Лебедева ДА, Козенева ВС, Хоцкин НВ, Амстиславский СЯ (2023) Анализ поведения и плотности нейронов в головном мозге мышей B6.Cg-Tg(Prnp-SNCA*A53T)23Mkle/J – модели болезни Паркинсона. Рос физиол журн им ИМ Сеченова 109: 1199–1216. [Rozhkova IN, Okotrub SV, Brusentsev EYu, Rakhmanova TA, Lebedeva DA, Kozeneva VS, Khotskin NV, Amstislavsky SYa (2023) Analysis of behavior and brain neuronal density in B6.Cg-Tg(Prnp-SNCA*A53T)23Mkle/J mice, a Parkinson’s disease model. Russ J Physiol 109: 1199–1216. (In Russ)]. https://doi.org/10.31857/S0869813923090091
  51. Раннева СВ, Брусенцевa ЕЮ, Игонина ТН, Рагаева ДС, Рожкова ИН, Ершовa НИ, Левинсон АЛ, Амстиславский СЯ (2020) Влияние культивирования эмбрионов на онтогенез потомства у млекопитающих. Онтогенез 51: 417–439. [Ranneva SV, Brusentsev EYu, Igonina TN, Ragaeva DS, Rozhkova IN, Ershov NI, Levinson AL, Amstislavsky SYa (2020) In vitro culture of preimplantation embryos and its influence on mammalian ontogenesis. Russ J Dev Biol 51: 417–439. (In Russ)]. https://doi.org/10.31857/S0475145020060075
  52. Rinaudo P, Schultz RM (2004) Effects of embryo culture on global pattern of gene expression in preimplantation mouse embryos. Reproduction 128: 301–311. https://doi.org/10.1530/rep.1.00297
  53. Paxinos G, Franklin K (2012) Mouse brain in stereotaxic coordinates. 4th ed. Acad Press.
  54. Carriere CH, Kang NH, Niles LP (2017) Bilateral upregulation of α-synuclein expression in the mouse substantia nigra by intracranial rotenone treatment. Exp Toxicol Pathol 69: 109–114. https://doi.org/10.1016/j.etp.2016.12.007.
  55. Hallett PJ, McLean JR, Kartunen A, Langston JW, Isacson O (2012) α-Synuclein overexpressing transgenic mice show internal organ pathology and autonomic deficits. Neurobiol Dis. 47: 258–267. https://doi.org/10.1016/j.nbd.2012.04.009.
  56. Kato M, Kimura M (1992) Effects of reversible blockade of basal ganglia on a voluntary arm movement. J Neurophysiol 68: 1516–1534. https://doi.org/10.1152/jn.1992.68.5.1516
  57. Cardoso HD, Passos PP, Lagranha CJ, Ferraz AC, Santos Junior EF, Oliveira RS, Oliveira PE, Santos Rde C, Santana DF, Borba JM, Rocha-de-Melo AP, Guedes RC, Navarro DM, Santos GK, Borner R, Picanco-Diniz CW, Beltrao EI, Silva JF, Rodrigues MC, Andrade da Costa BL (2012) Differential vulnerability of substantia nigra and corpus striatum to oxidative insult induced by reduced dietary levels of essential fatty acids. Front Hum Neurosci 6: 249. https://doi.org/10.3389/fnhum.2012.00249
  58. Schultz W, Ruffieux A, Aebischer P (1983) The activity of pars compacta neurons of the monkey substantia nigra in relation to motor activation. Exp Brain Res 51: 377–387.
  59. Chia SJ, Tan EK, Chao YX (2020) Historical perspective: models of Parkinson’s disease. Int J Mol Sci 21: 2464. https://doi.org/10.3390/ijms21072464
  60. Taguchi T, Ikuno M, Hondo M, Parajuli LK, Taguchi K, Ueda J, Sawamura M, Okuda S, Nakanishi E, Hara J, Uemura N, Hatanaka Y, Ayaki T, Matsuzawa S, Tanaka M, El-Agnaf OMA, Koike M, Yanagisawa M, Uemura MT, Yamakado H, Takahashi R (2020) α-SynucleinBAC transgenic mice exhibit RBD-like behaviour and hyposmia: a prodromal Parkinson’s disease model. Brain 143: 249–265. https://doi.org/10.1093/brain/awz380
  61. Wang Y, Sun Z, Du S, Wei H, Li X, Li X, Shen J, Chen X, Cai Z (2022) The increase of α-synuclein and alterations of dynein in A53T transgenic and aging mouse. J Clin Neurosci 96: 154–162. https://doi.org/10.1016/j.jocn.2021.11.002
  62. Kalia LV, Kalia SK, McLean PJ, Lozano AM, Lang AE (2013) α-Synuclein oligomers and clinical implications for Parkinson disease. Ann Neurol 73: 155–169.
  63. Wong YC, Krainc D (2017) α-synuclein toxicity in neurodegeneration: mechanism and therapeutic strategies. Nat Med 23: 1–13. https://doi.org/10.1038/nm.4269
  64. Albers JA, Chand P, Anch AM (2017) Multifactorial sleep disturbance in Parkinson’s disease. Sleep Med 35: 41–48. https://doi.org/10.1016/j.sleep.2017.03.026
  65. Braak H, Rub U, Gai WP, Del Tredici K (2003) Idiopathic Parkinson’s disease: Possible routes by which vulnerable neuronal types may be subject to neuroinvasion by an unknown pathogen. J Neural Transm 110: 517–536. https://doi.org/0.1007/s00702-002-0808-2
  66. Oaks AW, Frankfurt M, Finkelstein DI, Sidhu A (2013) Age-dependent effects of A53T alpha-synuclein on behavior and dopaminergic function. PLoS One 8: e60378. https://doi.org/10.1371/journal.pone.0060378
  67. Kleijkers SH, Eijssen LM, Coonen E, Derhaag JG, Mantikou E, Jonker MJ, Mastenbroek S, Repping S, Evers JL, Dumoulin JC, van Montfoort AP (2015) Differences in gene expression profiles between human preimplantation embryos cultured in two different IVF culture media. Hum Reprod 30: 2303–2311. https://doi.org/10.1093/humrep/dev179
  68. Ducreux B, Patrat C, Trasler J, Fauque P (2024) Transcriptomic integrity of human oocytes used in ARTs: technical and intrinsic factor effects. Hum Reprod Update 30: 26–47. https://doi.org/10.1093/humupd/dmad025
  69. Lane M, Gardner DK (1998) Amino acids and vitamins prevent culture-induced metabolic perturbations and associated loss of viability of mouse blastocysts. Hum Reprod 13: 991–997. https://doi.org/10.1093/humrep/13.4.991
  70. Alonso-Vanegas MA, Fawcett JP, Causing CG, Miller FD, Sadikot AF (1999) Characterization of dopaminergic midbrain neurons in a DBH:BDNF transgenic mouse. J Comp Neurol 413: 449–462. https://doi.org/10.1002/(sici)1096-9861(19991025)413:3<449::aid-cne7>3.0.co;2-2
  71. Blesa J, Trigo-Damas I, Dileone M, del Rey NL-G, Hernandez LF, Obeso JA (2017) Compensatory mechanisms in Parkinson’s disease: Circuits adaptations and role in disease modification. Exp Neurol 298: 148–161. https://doi.org/10.1016/j.expneurol.2017.10.002
  72. Nakashima A, Ota A, Kaneko YS, Nori K, Nagasaki H, Nagatsu T (2013) A possible pathophysiological role of tyrosine hydroxylase in Parkinson’s disease suggested by postmortem brain biochemistry: a contribution for the special 70th birthday symposium in honor of Prof. Peter Riederer. J Neural Transm 120: 49–54. https://doi.org/10.1007/s00702-012-0828-5
  73. Kozina EA, Khakimova GR, Khaindrava VG, Kucheryanu VG, Vorobyeva NE, Krasnov AN, Georgieva SG, Kerkerian Le-Goff L, Ugrumov MV (2014) Tyrosine hydroxylase expression and activity in nigrostriatal dopaminergic neurons of MPTP-treated mice at the presymptomatic and symptomatic stages of parkinsonism. J Neurol Sci 340(1–2): 198–207. https://doi.org/10.1016/j.jns.2014.03.028
  74. Calo L, Wegrzynowicz M, Santivañez-Perez J, Grazia Spillantini M (2016) Synaptic failure and α-synuclein. Mov Disord. 31(2): 169–177. https://doi.org/10.1002/mds.26479.
  75. Morris HR, Spillantini MG, Sue CM, Williams-Gray CH (2024) The pathogenesis of Parkinson's disease. Lancet 403(10423): 293–304. https://doi.org/10.1016/S0140-6736(23)01478-2
  76. Salvatore MF (2024) Dopamine Signaling in Substantia Nigra and Its Impact on Locomotor Function – Not a New Concept, but Neglected Reality. Int J Mol Sci 25(2): 1131. https://doi.org/10.3390/ijms25021131
  77. Giustiniani A, Quartarone A (2024) Defining the concept of reserve in the motor domain: a systematic review. Front Neurosci 18: 1403065. https://doi.org/10.3389/fnins.2024.1403065

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2. Fig. 1. Experimental design. ART – assisted reproductive technologies; B6.Cg-Tg – transgenic model of Parkinson's disease; WT – wild type (C57BL/6); WT CTL group – C57BL/6 males born naturally: the number of animals taken for the study in the rotarod test n = 14, for brain assessment n = 9; B6.Cg-Tg CTL group – B6.Cg-Tg males born naturally: the number of animals taken for the study in the rotarod test and for brain assessment n = 9; WT ET group – C57BL/6 males born using ART: the number of animals taken for the study in the rotarod test and for brain assessment n = 4; Group B6.Cg-Tg ET – B6.Cg-Tg males born using ART: number of animals taken for the study in the rotarod test and for brain assessment n = 4.

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3. Fig. 2. Rotarod test. Latent time to animal fall. WT CTL – wild-type C57BL/6 offspring obtained by natural mating without assisted reproductive technologies (ART); B6.Cg-Tg CTL – B6.Cg-Tg offspring obtained without ART; WT ET – wild-type C57BL/6 offspring obtained with ART; B6.Cg-Tg ET – B6.Cg-Tg offspring obtained with ART. * p < 0.05 between WT ET and WT CTL; # p < 0.05 between B6.Cg-Tg ET and WT ET.

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4. Fig. 3. Density of neurons in the substantia nigra pars compacta (SNpc), neurons are labeled with antibodies against the neuronal marker (NeuN). (a) Number of neurons per mm3; (b) Schematic representation of the studied area in the brain. (c–f) Photomicrographs of sections in the substantia nigra pars compacta; (c) Wild-type C57BL/6 progeny obtained without the use of ART (WT CTL); (d) B6.Cg-Tg progeny obtained without the use of ART (B6.Cg-Tg CTL); (e) Wild-type C57BL/6 progeny obtained with the use of ART (WT ET); (f) B6.Cg-Tg progeny obtained with the use of ART (B6.Cg-Tg ET). Dotted lines indicate the borders of the substantia nigra. * p < 0.05 between B6.Cg-Tg CTL and WT CTL, and between WT ET and WT CTL; + p < 0.05 between B6.Cg-Tg ET and B6.Cg-Tg CTL; # p < 0.05 between B6.Cg-Tg ET and WT ET.

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5. Fig. 4. Density of dopaminergic neurons in the substantia nigra pars compacta (SNC), neurons labeled with antibodies against tyrosine hydroxylase (TH). (a) Number of neurons in mm3; (b) Schematic representation of the studied area in the brain. (c–f) Photomicrographs of sections in this area; (c) Wild-type C57BL/6 progeny obtained without ART (WT CTL); (d) B6.Cg-Tg progeny obtained without ART (B6.Cg-Tg CTL); (e) Wild-type C57BL/6 progeny obtained with ART (WT ET); (f) B6.Cg-Tg progeny obtained with ART (B6.Cg-Tg ET). * p < 0.05 between B6.Cg-Tg CTL and WT CTL, and between WT ET and WT CTL.

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6. Fig. 5. Density of neurons with alpha-synuclein in the substantia nigra pars compacta (SNC), neurons are labeled with antibodies against alpha-synuclein, neuronal nuclei are stained with DAPI; (a–d) – photomicrographs of sections in this region (entire SNpc; corresponding fragment); (a) – wild-type C57BL/6 progeny obtained without ART (WT CTL); (b) – B6.Cg-Tg progeny obtained without ART (B6.Cg-Tg CTL); (c) – wild-type C57BL/6 progeny obtained with ART (WT ET); (d) – B6.Cg-Tg progeny obtained with ART (B6.Cg-Tg ET); (e) – number of neurons in mm3. (f) – schematic designation of the studied region in the brain. Dotted lines indicate the boundaries of the substantia nigra. *** p < 0.001 between B6.Cg-Tg CTL and WT CTL; ++ p < 0.01 between B6.Cg-Tg ET and B6.Cg-Tg CTL; ### p < 0.001 between B6.Cg-Tg ET and WT ET.

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