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Maternal treatment with dexamethasone during gestation alters sexual development markers in the F1 and F2 male offspring of Wistar rats

Published online by Cambridge University Press:  31 August 2016

S. O. Jeje  and
Y. Raji
S. O. Jeje*
Affiliation:
Laboratory for Reproductive Physiology and Developmental Programming, Department of Physiology, University of Ibadan, Ibadan, Nigeria Department of Human Physiology, Cross River University of Technology, Okuku Campus, Cross River State, Nigeria
Y. Raji
Affiliation:
Laboratory for Reproductive Physiology and Developmental Programming, Department of Physiology, University of Ibadan, Ibadan, Nigeria
*
*Address for correspondence: S. O. Jeje, Department of Physiology, Cross River University of Technology, Okuku Campus, Cross River State, +234 Nigeria. (Email [email protected])
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Abstract

Maternal treatment with dexamethasone (Dex) in threatening preterm delivery alters activities at the hypothalamic–pituitary–adrenal axis in the offspring. This alteration may interfere with reproductive function. The impact of gestational Dex exposure on male reproductive function of the offspring was investigated. A total of 25 pregnant rats randomly assigned to five groups (n=5) were treated with normal saline (control), Dex (100 μg/kg/day sc) during gestation days (GD) 1–7, 8–14, 15–21 and 1–21, respectively. Birth weight, anogenital distance (AGD), pubertal age, sperm parameters, hormonal profile and histopathology of testis and epididymis were determined in the F1 and F2 offspring. Results showed a significant increase (P<0.05) in pubertal age, serum corticosterone and gonadotropin-releasing hormone (GnRH) levels in the male offspring of DexGD 15–21 and 1–21 groups and a significant decrease (P<0.05) in serum testosterone, luteinizing hormone, birth weight and AGD at birth in the male F1 offspring. In the F2 offspring, there was a significant reduction (P<0.05) in serum corticosterone, testosterone, follicle-stimulating hormone and GnRH when compared with the control. Dex treatment at GD 15–21 and 1–21 significantly reduced (P<0.05) sperm motility and normal morphology in the F1 and F2 offspring. Maternal Dex treatment in rats during late gestation may disrupt sexual development markers in the F1 and F2 male offspring.

Keywords

dexamethasonegestationpubertal age
Type
Original Article
Information
Journal of Developmental Origins of Health and Disease , Volume 8 , Issue 1 , February 2017 , pp. 101 - 112
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Copyright
© Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2016 

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References

1. Environmental Protection Agency United States. Guideline for reproductive toxicity risk assessment. Fed Regist. 1996; 61, 56274–56322.Google Scholar
2. Tegethoff, M, Pryce, C, Manischmidt, G. Effects of intrauterine exposure to synthetic glucocorticoids on fetal, newborn and infant HPA axis function in humans: a systematic review. Endocr Rev. 2009; 30, 753–789.Google Scholar
3. Drake, AJ, Tang, JI, Nyirenda, MJ. Mechanisms underlying the role of glucocorticoids in early life programming of adult disease. Clin Sci. 2007; 113, 219–232.Google Scholar
4. Singh, RR, Cuffe, JSM, Moritz, KM. Short and long term exposure to natural and synthetic glucocorticoids during development. Proc Aust Physiol Soc. 2012; 43, 57–69.Google Scholar
5. Peiser, PW, Azziz, R, Baskin, LS, et al. Congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2010; 95, 4133–4160.Google Scholar
6. Clayton, DB, Brook, JW III. In utero intervention for urologic diseases. Nat Rev Urol. 2012; 9, 207–217.CrossRefGoogle ScholarPubMed
7. Benediktsson, R, Lindsay, RS, Noble, J, Seckl, JR, Edwards, CR. Glucocorticoid exposure in utero: new model for adult hypertension. Lancet. 1993; 341, 339–341.Google Scholar
8. Nyirenda, MJ, Lindsay, RS, Kenyon, CJ, Burchell, A, Seckl, JR. Glucocorticoids exposure in late gestation permanently programs rat hepatic phosphoenolpyruvatecarboxykinase and glucocorticoids receptor expression and causes glucose intolerance in adult offspring. J Clin Invest. 1998; 101, 2174–2181.Google Scholar
9. deVries, A, Holmes, MC, Heijnis, A, et al. Prenatal dexamethasone exposure induces changes in nonhuman primate offspring cardiometabolic and hypothalamic–pituitary–adrenal axis function. J Clin Invest. 2007; 117, 1058–1067.Google Scholar
10. Main, KM, Jensen, RB, Asklund, C, Hoi-Hansen, CE, Skakkebaek, NE. Low birth weight and male reproductive function. Horm Res. 2006; 65, 116–122.Google Scholar
11. Sharpe, RM, Shkakkebaek, NE. Testicular dysgenesis syndrome: mechanistic insights and potential new downstream effects. Fertil Steril. 2008; 89, e33–e38.Google Scholar
12. Kapoor, A, Dunn, E, Kostak, A, Andrews, MH, Mathews, SG. Fetal programming of hypothalamo-pituitary adrenal function: prenatal stress and glucocorticoids. J Physiol. 2006; 572, 31–44.CrossRefGoogle ScholarPubMed
13. Jeje, SO, Raji, Y. Effects of maternal dexamethasone exposure on hematological indices in the male offspring. Int J Biol Chem Sci. 2015; 9, 48–55.Google Scholar
14. Drake, AJ, Walker, BR. The intergenerational effects of fetal programming: non-genomic mechanisms for the inheritance of low birth weight and cardiovascular risk. J Endocrinol. 2004; 180, 1–16.CrossRefGoogle ScholarPubMed
15. Drake, AJ, Walker, BR, Seckl, JR. Intergenerational consequences of fetal programming by in utero exposure to glucocorticoids in rats. Am J Physiol Regul Integr Comp Physiol. 2005; 288, R34–R38.Google Scholar
16. Aron, DC, Finding, JW, Tyrrell, JB. Glucocorticoids and adrenal androgen. In Greenspan’s Basic and Clinical Endocrinology 8th edn (eds. Gardner DG, Shoback, D), 2007; pp. 246–295. McGraw Hill: USA.Google Scholar
17. Mattison, DR. Clinical manifestations of ovarian toxicity. In Reproductive Toxicology (ed. Dixon, RL), 1985; pp. 109–130. Raven Press: New York.Google Scholar
18. Schardein, JL. Chemically Induced Birth Defects. 1993. Marcel Dekker: New York.Google Scholar
19. Drake, AJ, Van den, SD, Scott, HM, et al. Glucocorticoids amplify dibutyl phthalate-induced disruption of testosterone production and male reproductive development. Endocrinology. 2009; 150, 5055–5064.Google Scholar
20. Smith, JT, Waddell, BJ. Increased fetal glucocorticoids exposure delays puberty onset in postnatal life. Endocrinology. 2000; 141, 2422–2428.Google Scholar
21. Ostby, JS, Gray, E Jr. Transgenerational (in utero and lactational) exposure to investigate the effects of endocrine disrupting compounds in rats. Curr Protoc Toxicol. 2004; 16, 16.8.Google Scholar
22. Marcondes, FK, Bianchi, FJ, Tanmo, AP. Determination of the estrous cycle phases of rats: some helpful considerations. Braz J Biol. 2002; 62, 609–614.Google Scholar
23. Raji, Y, Udoh, US, Mewoka, OO, Ononye, FC, Bolarinwa, AF. Implication of reproductive endocrine malfunction in male antifertility efficacy of Azadirachtaindica extract in rats. Afr J Med Sci. 2003; 32, 159–165.Google Scholar
24. Akinloye, AK, Abatan, MO, Alaka, OO, Oke, BO. Histomorphometric and histopathological studies on the effect of Calotropisprocera (giant milkweek) on the male reproductive organs of Wistar rats. Afr J Biomed Res. 2002; 5, 57–61.Google Scholar
25. Raji, Y, Bolarinwa, AF. Anti fertility activity of Quassiaamara in male rats in vivo study. Life Sci. 1997; 11, 1067–1074.Google Scholar
26. Moritz, KM, Singh, RR, Probyn, ME, Denton, KM. Developmental programming of a reduced nephron endowment: more than just a baby’s birth weight. Am J Physiol Renal Physiol. 2009; 296, F1–F9.Google Scholar
27. Woods, LL, Weeks, DA. Prenatal programming of adult blood pressure: role of maternal corticosteroids. Am J Physiol Regul Integr Comp Physiol. 2005; 289, R955–R962.Google Scholar
28. Somm, E, Vauthay, DM, Guerardel, A, et al. Early metabolic defects in dexamethasone exposed and undernourished growth restricted rats. Plos One. 2012; 7, e50131.Google Scholar
29. Pratt, L, Magness, R, Phernetton, T, et al. Repeated use of betamethasone in rabbits: effects of treatment variation on adrenal suppression, pulmonary maturation, and pregnancy outcome. Am J Obstetr Gynecol. 1999; 180, 995–1005.CrossRefGoogle ScholarPubMed
30. Homar, V, Grosek, S, Battelino, T. High dose of methylprednisolone in a pregnant woman with Crohn’s disease and adrenal suppression in her newborn. Neonatology. 2008; 94, 306–309.Google Scholar
31. Kurtoglu, S, Sarici, D, Akin, MA, et al. Fetal adrenal suppression due to maternal corticosteroid use: case report. J Clin Res Pediatr Endocrinol. 2001; 3, 160–162.Google Scholar
32. Sharp, RM. Hormones and testis development and the possible effects of environmental chemicals. Toxicol Lett. 2001; 120, 221–232.Google Scholar
33. Rivas, A, Fisher, JS, Mckinnell, C, Atanassova, N, Sharpe, RM. Induction of reproductive tract developmental abnormalities in the male rat by lowering androgen production or action in combination with a low dose of diethylstilbesterol: evidence for importance of the androgen–estrogen balance. Endocrinology. 2002; 143, 4797–4808.Google Scholar
34. Welsh, M, Saunders, PT, Fsiken, M, et al. Identification in rats of aprogramming window for reproductive tract masculinisation, disruption of which leads to hypospadias and cryptochidism. J Clin Invest. 2008; 118, 1479–1490.Google Scholar
35. Meaney, MJ, Viau, V, Bhatnagar, S, et al. Cellular mechanisms underlying the development and expression of individual differences in the hypothalamic-pituitary-adrenal stress response. J Steroid Biochem Mol Biol. 1991; 39, 265–274.CrossRefGoogle ScholarPubMed
36. Daikoku, S, Koide, I. Spatiotemporal appearance of developing LHRH neurons in the rat brain. J Comp Neurol. 1998; 393, 34–47.Google Scholar
37. Kilen, SM, Szabo, M, Strasser, GA, et al. Corticosterone selectively increases follicle-stimulating hormone β-subunit messenger ribonucleic acid in primary anterior pituitary cell culture without affecting its half-life. Endocrinology. 1996; 137, 3802–3807.Google Scholar
38. Walsh, LP, Stocco, DM. Effects of lindane on steroidogenesis and steroidogenic acute regulatory protein expression. Biol Reprod. 2000; 63, 1024–1033.Google Scholar
39. Levitt, NS, Lindsay, RS, Holmes, MC, Seckl, JR. Dexamethasone in the last week of pregnancy attenuate hippocampal glucocorticoid receptor gene expression and elevate blood pressure in the adult offspring in the rat. Neuroendocrinology. 1996; 64, 412–418.Google Scholar
40. Welberg, LAM, Seckl, JR. Prenatal stress, glucocorticoids and the programming of the brain. J Neuroendocrinol. 2001; 13, 113–128.Google Scholar
41. Dunn, E, Owen, D, Kostaki, A, Matthew, SG. Prenatal glucocorticoid exposure affects reproductive capacity and adrenocortical function in mature female guinea pig offspring. Pediatr Res. 2005; 58, 0-008.Google Scholar
42. Recabarren, SE, Rojas-Garcia, PP, Recabarren, MP, et al. Prenatal testosterone excess reduces sperm count and motility. Endocrinology. 2008; 149, 6444–6448.Google Scholar
43. Barker, DJP. Mothers, Babies and Disease in Later Life. 1994. BMJ Publishing: London.Google Scholar
44. Rey, R, Lukas-Croisier, C, Lasala, C, Bedecarras, P. AMH/MIS: what we know already about the gene, the protein and its regulation. Mol Cell Endocrinol. 2003; 211, 21–31.Google Scholar
45. Sharpe, RM, McKinnell, C, Kivlin, C, Fisher, JS. Proliferation and functional maturation of Sertoli cells, and their relevance to disorders of testis function in adulthood. Reproduction. 2003; 125, 769–784.Google Scholar
46. Ganong, WF. Review of Medical Physiology, 22nd edn, 2005. McGraw Hill: Singapore.Google Scholar
47. Rodger, BA, Chrisopher, PM, Leu, NA, Bale, TL. Transgenerational epigenetic programming via sperm microRNA recapitulates effects of paternal stress. Proc Natl Acad Sci U S A. 2015; 112, 13699–13704.Google Scholar
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