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Radioactive Iodine-induced hypothyroidism interferes with the maturation of reproductive organs during puberty in immature female rats

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Abstract

Animal and human studies suggest that thyroid hormone may have critical roles in the development of the ovary. For example, thyroid deficiency disrupts the ovarian microarchitecture and menstrual cycle in neonate and adult women, respectively. Therefore, it is conceivable that thyroid deficiency might disrupt sexual maturation during the peri-pubertal period. To investigate the impact of radioactive iodine-induced thyroid deficiency on reproductive organs throughout puberty, immature female rats were given water containing radioactive iodine (0.37 MBq/g body weight) twice, on postnatal days 22 and 29. Radioactive iodine-induced hypothyroidism was revealed by low free thyroxin levels. Thyroid deficiency delayed the onset of vaginal opening, reduced ovarian weight and the number of medium-sized follicles and led to elongated uteri. However, there was no effect on the estrous cycle or absolute uterus weight. We conclude that radioactive iodine-induced thyroid deficiency delays sexual maturation and alters normal ovarian growth in peri-pubertal rats.

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References

  1. Hanley P, Lord K, Bauer AJ (2016) Thyroid disorders in children and adolescents: a review. JAMA Pediatr 170:1008–1019. https://doi.org/10.1001/jamapediatrics.2016.0486

    Article  Google Scholar 

  2. Brown RS (2013) Autoimmune thyroiditis in childhood. J Clin Res Pediatr Endocrinol 5(Suppl 1):45–49. https://doi.org/10.4274/Jcrpe.855

    Article  Google Scholar 

  3. Sheehan MT, Doi SA (2016) Transient hypothyroidism after radioiodine for Graves’ disease: challenges in interpreting thyroid function tests. Clin Med Res 14:40–45. https://doi.org/10.3121/cmr.2015.1297

    Article  CAS  Google Scholar 

  4. Wasniewska M, Aversa T, Salerno M, Corrias A, Messina MF, Mussa A et al (2015) Five-year prospective evaluation of thyroid function in girls with subclinical mild hypothyroidism of different etiology. Eur J Endocrinol 173:801–808. https://doi.org/10.1530/EJE-15-0484

    Article  CAS  Google Scholar 

  5. Abbassi V, Rigterink E, Cancellieri R (1980) Clinical recognition of juvenile hypothyroidism in the early stage. Clin Pediatr (Phila) 19:782–786. https://doi.org/10.1177/000992288001901201

    Article  CAS  Google Scholar 

  6. Setian N (2007) Hypothyroidism in children: diagnosis and treatment. J Pediatr (Rio J) 83:S209–S216. https://doi.org/10.2223/JPED.1716

    Article  Google Scholar 

  7. Mullur R, Liu Y-Y, Brent GA (2014) Thyroid hormone regulation of metabolism. Physiol Rev 94:355–382. https://doi.org/10.1152/physrev.00030

    Article  CAS  Google Scholar 

  8. Ojeda S, Smith-White S, Advis J, Andrews W, Aguado L (1990) First preovulatory gonadotropin surge in the rodent. Control of the onset of puberty Baltimore. Williams & Wilkins, pp 156–182

    Google Scholar 

  9. Calcaterra V, Nappi RE, Regalbuto C, De Silvestri A, Incardona A, Amariti R et al (2020) Gender differences at the onset of autoimmune thyroid diseases in children and adolescents. Front Endocrinol 11:229. https://doi.org/10.3389/fendo.2020.00229

    Article  Google Scholar 

  10. Raychaudhuri M, Sanyal D (2020) Juvenile hypothyroidism: a clinical perspective from Eastern India. Indian J Endocrinol Metab 24:260–264. https://doi.org/10.4103/ijem.IJEM_627_19

    Article  CAS  Google Scholar 

  11. Tsutsui K, Son YL, Kiyohara M, Miyata I (2018) Discovery of GnIH and its role in hypothyroidism-induced delayed puberty. Endocrinology 159:62–68. https://doi.org/10.1210/en.2017-00300

    Article  CAS  Google Scholar 

  12. Picut CA, Dixon D, Simons ML, Stump DG, Parker GA, Remick AK (2015) Postnatal ovary development in the rat: morphologic study and correlation of morphology to neuroendocrine parameters. Toxicol Pathol 43:343–353. https://doi.org/10.1177/0192623314544380

    Article  CAS  Google Scholar 

  13. Everett JW (1989) Neurobiology of reproduction in the female laboratory rat. Springer-Verlag

    Book  Google Scholar 

  14. Goldman JM, Murr AS, Cooper RL (2007) The rodent estrous cycle: characterization of vaginal cytology and its utility in toxicological studies. Birth Defects Res B Dev Reprod Toxicol 80:84–97. https://doi.org/10.1002/bdrb.20106

    Article  CAS  Google Scholar 

  15. Myers M, Britt KL, Wreford NGM, Ebling FJ, Kerr JB (2004) Methods for quantifying follicular numbers within the mouse ovary. Reproduction 127:569–580. https://doi.org/10.1530/rep.1.00095

    Article  CAS  Google Scholar 

  16. Gorbman A (1950) Functional and structural changes consequent to high dosages of radioactive iodine. J Clin Endocrinol Metab 10:1177–1191. https://doi.org/10.1210/jcem-10-10-1177

    Article  CAS  Google Scholar 

  17. Alva-Sánchez C, Pacheco-Rosado J, Fregoso-Aguilar T, Villanueva I (2012) The long-term regulation of food intake and body weight depends on the availability of thyroid hormones in the brain. Neuro Endocrinol Lett 33:703–708

    Google Scholar 

  18. Conti MI, Martínez MP, Olivera MI, Bozzini C, Mandalunis P, Bozzini CE et al (2009) Biomechanical performance of diaphyseal shafts and bone tissue of femurs from hypothyroid rats. Endocrine 36:291–298. https://doi.org/10.1007/s12020-009-9212-0

    Article  CAS  Google Scholar 

  19. Pearce EN (2012) Thyroid hormone and obesity. Curr Opin Endocrinol Diabetes Obes 19:408–413. https://doi.org/10.1097/MED.0b013e328355cd6c

    Article  CAS  Google Scholar 

  20. Choi J-S, An H-Y, Park IS, Kim S-K, Kim Y-M, Lim J-Y (2016) Radioprotective effect of epigallocatechin-3-gallate on salivary gland dysfunction after radioiodine ablation in a murine model. Clin Exp Otorhinolaryngol 9:244–251. https://doi.org/10.21053/ceo.2015.01011

    Article  CAS  Google Scholar 

  21. Kaplowitz PB, Slora EJ, Wasserman RC, Pedlow SE, Herman-Giddens ME (2001) Earlier onset of puberty in girls: relation to increased body mass index and race. Pediatrics 108:347–353. https://doi.org/10.1542/peds.108.2.347

    Article  CAS  Google Scholar 

  22. Bagheripuor F, Ghanbari M, Piryaei A, Ghasemi A (2018) Effects of fetal hypothyroidism on uterine smooth muscle contraction and structure of offspring rats. Exp Physiol 103:683–692. https://doi.org/10.1113/EP086564

    Article  CAS  Google Scholar 

  23. Wei Q, Fedail JS, Kong L, Zheng K, Meng C, Fadlalla MB, Shi F (2018) Thyroid hormones alter estrous cyclicity and antioxidative status in the ovaries of rats. Anim Sci J 89:513–526. https://doi.org/10.1111/asj.12950

    Article  CAS  Google Scholar 

  24. Ojeda SR, Skinner MK (2006) Puberty in the rat. Knobil and Neill’s physiology of reproduction. Elsevier Inc., pp 2061–2126. https://doi.org/10.1016/B978-012515400-0/50043-9

    Book  Google Scholar 

  25. Hapon MB, Gamarra-Luques C, Jahn GA (2010) Short term hypothyroidism affects ovarian function in the cycling rat. Reprod Biol Endocrinol 8:1–11. https://doi.org/10.1186/1477-7827-8-14

    Article  CAS  Google Scholar 

  26. Li Y, Kumazawa T, Ishiguro T, Kawakami Y, Nishitani H, Tagawa Y, Matsumoto Y (2011) Hypothyroidism caused by phenobarbital affects patterns of estrous cyclicity in rats. Congenit Anom 51:55–61. https://doi.org/10.1111/j.1741-4520.2011.00314.x

    Article  CAS  Google Scholar 

  27. Gabriel SM, Roncancio JR, Ruiz NS (1992) Growth hormone pulsatility and the endocrine milieu during sexual maturation in male and female rats. Neuroendocrinology 56:619–625. https://doi.org/10.1159/000126284

    Article  CAS  Google Scholar 

  28. Hansen KA, Tho SP, Hanly M, Moretuzzo RW, McDonough PG (1997) Massive ovarian enlargement in primary hypothyroidism. Fertil Steril 67:169–171. https://doi.org/10.1016/s0015-0282(97)81876-6

    Article  CAS  Google Scholar 

  29. Chattopadhyay A, Kumar V, Marulaiah M (2003) Polycystic ovaries, precocious puberty and acquired hypothyroidism: the Van Wyk and Grumbach syndrome. J Pediatr Surg 38:1390–1392. https://doi.org/10.1016/s0022-3468(03)00403-2

    Article  Google Scholar 

  30. Krassas GE (2000) Thyroid disease and female reproduction. Fertil Steril 74:1063–1070. https://doi.org/10.1016/s0015-0282(00)01589-2

    Article  CAS  Google Scholar 

  31. Byskov AGS (1974) Cell kinetic studies of follicular atresia in the mouse ovary. Reproduction 37:277–285. https://doi.org/10.1530/jrf.0.0370277

    Article  CAS  Google Scholar 

  32. Meng L, Rijntjes E, Swarts HJ, Keijer J, Teerds KJ (2017) Prolonged hypothyroidism severely reduces ovarian follicular reserve in adult rats. J Ovarian Res 10:1–8. https://doi.org/10.1186/s13048-017-0314-7

    Article  CAS  Google Scholar 

  33. Bridges N, Cooke A, Healy M, Hindmarsh P, Brook C (1996) Growth of the uterus. Arch Dis Child 75:330–331. https://doi.org/10.1136/adc.75.4.330

    Article  CAS  Google Scholar 

  34. Couse JF, Korach KS (1999) Estrogen receptor null mice: what have we learned and where will they lead us? Endocr Rev 20:358–417. https://doi.org/10.1210/edrv.20.3.0370

    Article  CAS  Google Scholar 

  35. Rodríguez-Castelán J, Anaya-Hernández A, Méndez-Tepepa M, Martínez-Gómez M, Castelán F, Cuevas-Romero E (2017) Distribution of thyroid hormone and thyrotropin receptors in reproductive tissues of adult female rabbits. Endocr Res 42:59–70. https://doi.org/10.1080/07435800.2016.1182185

    Article  CAS  Google Scholar 

  36. Armada-Dias L, Carvalho J, Breitenbach M, Franci C, Moura E (2001) Is the infertility in hypothyroidism mainly due to ovarian or pituitary functional changes? Braz J Med Biol Res 34:1209–1215. https://doi.org/10.1590/s0100-879x2001000900015

    Article  CAS  Google Scholar 

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Acknowledgements

JK and KYR participated in data analysis, experimental work and development of the manuscript, and JR participated in the design of the study, data analysis, and supervision. JR takes responsibility for the integrity of the data analysis. All authors read and approved the final manuscript.

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This work was supported by the research fund of Hanyang University (HY-2017).

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Correspondence to Jaesook Roh.

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Keum, J., Ryu, KY. & Roh, J. Radioactive Iodine-induced hypothyroidism interferes with the maturation of reproductive organs during puberty in immature female rats. Toxicol Res. 39, 53–60 (2023). https://doi.org/10.1007/s43188-022-00147-z

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