Development and Reproduction (한국발생생물학회지:발생과생식)

The Korean Society of Developmental Biology (한국발생생물학회)
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Effects of Maternal Hypothyroidism on the Pubertal Development in Female Rat Offspring

  • Received : 2021.04.03
  • Accepted : 2021.06.01
  • Published : 2021.06.30
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Abstract

The present study was performed to investigate the effect of maternal hypothyroidism and puberty onset in female rat pups. To do this, we employed propylthiouracil (PTU) to prepare a hypothyroid rat model. Pregnant rats were treated with PTU (0.025%) in drinking water from gestational day 14 to postnatal day 21 of offspring. Comparison of general indices such as body and tissue weights and puberty indices such as vaginal opening (VO) and tissue histology between control and PTU-treated rats were conducted. There was no significant difference in the date of VO between control and PTU group. The body weights of the PTU group were significantly lower, only 36.8% of the control group (p<0.001). Although the absolute thyroid weight was not changed by PTU treatment, the relative weight increased significantly about 2.8 times (p<0.001), indicating that hypothyroidism was successfully induced. On the other hand, the absolute weights of the ovary and uterus were markedly decreased by PTU administration (p<0.001), and the relative weight was not significantly changed. The ovarian histology of PTU group revealed the advanced state of differentiation (i.e., presence of corpora lutea). Inversely, the uterine histology of PTU group showed underdeveloped structures compared those in control group. Taken together, the present study demonstrates that our maternal hypothyroidism model resulted in minimal effect on pubertal development symbolized by VO despite of huge retardation in somatic growth. More sophisticatedly designed hypothyroidism model will be helpful to achieve a better understanding of pubertal development and related disorders.

Keywords

Acknowledgement

This research was funded by a 2020 research Grant from Sangmyung University (2020-A000-0172).

References

  1. Anasti JN, Flack MR, Froehlich J, Nelson LM, Nisula BC (1995) A potential novel mechanism for precocious puberty in juvenile hypothyroidism. J Clin Endocrinol Metab 80:276-279. https://doi.org/10.1210/jc.80.1.276
  2. Castaneda Cortes DL, Langlois VS, Fernandino JI (2014) Crossover of the hypothalamic pituitary-adrenal/interrenal, -thyroid, and -gonadal axes in testicular development. Front Endocrinol 5:139. https://doi.org/10.3389/fendo.2014.00139
  3. Chiovato L, Magri F, Carle A (2019) Hypothyroidism in context: Where we've been and where we're going. Adv Ther 36:47-58. https://doi.org/10.1007/s12325-019-01080-8
  4. Choksi NY, Jahnke GD, St Hilaire C, Shelby M (2003) Role of thyroid hormones in human and laboratory animal reproductive health. Birth Defects Res B: Dev Reprod Toxicol 68:479-491. https://doi.org/10.1002/bdrb.10045
  5. Colledge NR, Walker BR, Ralston SH (2010) Davidson's Principles and Practice of Medicine. 21st ed. Elsevier, Edinburgh, UK.
  6. Counts D, Varma SK (2009) Hypothyroidism in children. Pediatr Rev 30:251-258. https://doi.org/10.1542/pir.30-7-251
  7. Doufas AG, Mastorakos G (2000) The hypothalamic-pituitary-thyroid axis and the female reproductive system. Ann N Y Acad Sci 900:65-76. https://doi.org/10.1111/j.1749-6632.2000.tb06217.x
  8. Dowling ALS, Martz GU, Leonard JL, Zoeller RT (2000) Acute changes in maternal thyroid hormone induce rapid and transient changes in gene expression in fetal rat brain. J Neurosci 20:2255-2265. https://doi.org/10.1523/JNEUROSCI.20-06-02255.2000
  9. El-Shafie KT (2003) Clinical presentation of hypothyroidism. J Family Community Med 10:55-58.
  10. Fekete C, Lechan RM (2014) Central regulation of hypothalamic-pituitary-thyroid axis under physiological and pathophysiological conditions. Endocr Rev 35:159-194. https://doi.org/10.1210/er.2013-1087
  11. Hall JE, Guyton A (2011) Guyton and Hall Textbook of Medical Physiology. 12th ed. Elsevier, Philadelphia, PA.
  12. Hapon MB, Varas SM, Gimenez MS, Jahn GA (2007) Reduction of mammary and liver lipogenesis and alteration of milk composition during lactation in rats by hypothyroidism. Thyroid 17:11-18. https://doi.org/10.1089/thy.2005.0267
  13. Idris I, Srinivasan R, Simm A, Page RC (2005) Maternal hypothyroidism in early and late gestation: Effects on neonatal and obstetric outcome. Clin Endocrinol 63:560-565. https://doi.org/10.1111/j.1365-2265.2005.02382.x
  14. Kiyohara M, Son YL, Tsutsui K (2017) Involvement of gonadotropin-inhibitory hormone in pubertal disorders induced by thyroid status. Sci Rep 7:1042. https://doi.org/10.1038/s41598-017-01183-8
  15. Lee SY, Jang YS, Lee YH, Seo HH, Noh KH, Lee SH (2009) Advanced onset of puberty in high-fat diet-fed immature female rats: Activation of KiSS-1 and GnRH expression in the hypothalamus. Dev Reprod 13:183-190.
  16. Mallela MK, Strobl M, Poulsen RR, Wendler CC, Booth CJ, Rivkees SA (2014) Evaluation of developmental toxicity of propylthiouracil and methimazole. Birth Defects Res B Dev Reprod Toxicol 101:300-307. https://doi.org/10.1002/bdrb.21113
  17. Mandel SJ, Cooper DS (2001) The use of antithyroid drugs in pregnancy and lactation. J Clin Endocrinol Metab 86:2354-2359. https://doi.org/10.1210/jcem.86.6.7573
  18. Shibutani M, Woo GH, Fujimoto H, Saegusa Y, Takahashi M, Inoue K, Hirose M, Nishikawa A (2009) Assessment of developmental effects of hypothyroidism in rats from in utero and lactation exposure to anti-thyroid agents. Reprod Toxicol 28:297-307. https://doi.org/10.1016/j.reprotox.2009.04.011
  19. Sun J, Shen X, Liu H, Lu S, Peng J, Kuang H (2021) Caloric restriction in female reproduction: Is it beneficial or detrimental? Reprod Biol Endocrinol 19:1. https://doi.org/10.1186/s12958-020-00681-1
  20. Tanaka T, Masubuchi Y, Okada R, Nakajima K, Nakamura K, Masuda S, Nakahara J, Maronpot R, Yoshida T, Koyanagi M, Hayashi SM, Shibutani M (2019) Ameliorating effect of postweaning exposure to antioxidant on disruption of hippocampal neurogenesis induced by developmental hypothyroidism in rats. J Toxicol Sci 44:357-372. https://doi.org/10.2131/jts.44.357
  21. Taylor PN, Albrecht D, Scholz A, Gutierrez-Buey G, Lazarus JH, Dayan CM, Okosieme OE (2018) Global epidemiology of hyperthyroidism and hypothyroidism. Nat Rev Endocrinol 14:301-316. https://doi.org/10.1038/nrendo.2018.18
  22. Tsutsui K, Son YN, 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
  23. Wilen R, Bastomsky CH, Naftolin F (1981) Control of puberty in female rats: The effect of PTU-induced hypothyroidism and systematic undernutrition. Pediatr Res 15:169-171. https://doi.org/10.1203/00006450-198102000-00019
  24. Zamoner A, Barreto KP, Filho DW, Sell F, Woehl VM, Guma FC, Pessoa-Pureur FR, Silva F (2008) Propylthiouracil-induced congenital hypothyroidism upregulates vimentin phosphorylation and depletes antioxidant defenses in immature rat testis. J Mol Endocrinol 40:125-135. https://doi.org/10.1677/JME-07-0089