Tohoku J. Exp. Med., 2017 March, 241(3)

Age-Dependent Effects of Prenatal Dexamethasone Exposure on Immune Responses in Male Rats

MING-YI CHOU,¹ LI-TUNG HUANG,¹ YOU-LIN TAIN,¹ HO-CHANG KUO,¹ MAO-MENG TIAO,¹ JIUNN-MING SHEEN,¹ CHIH-CHENG CHEN,¹ PI-LIEN HUNG,¹ KAI-SHENG HSIEH¹ and HONG-REN YU^1,2

¹Department of Pediatrics, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Kaohsiung, Taiwan
²Graduate Insititute of Clinical Medical Science, Chang Gung University College of Medicine, Taoyuan, Taiwan

Prenatal glucocorticoid therapy is indicated in preterm delivery to prevent respiratory distress. This study was designed to evaluate the age-dependent effects of prenatal dexamethasone (DEX) therapy on the immune system using a rat model. Pregnant Sprague-Dawley rats received an intraperitoneal injection of DEX (0.1 mg/kg/day) or saline (VEH) over gestational days 14-20. Male offspring were sacrificed at postnatal day 7 (D7; infant stage), D120 (young adult stage), and D180 (adult stage) for evaluation of leukocyte subsets and isolation of splenocytes. The production of innate and adaptive immune cytokines was assessed from the culture supernatants of splenocytes, stimulated with lipopolysaccharide and concanavalin A, respectively. For innate cytokines, the levels of interferon gamma inducible protein 10 were significantly higher, but those of tumor necrosis factor-α were significantly lower, in the culture medium of splenocytes prepared from the DEX group at D120 than those in the VEH group. For adaptive cytokines, the levels of interleukin-4 (IL-4) were significantly higher at D7 and those of IL-10 were significantly higher at D120 after prenatal exposure to DEX. We also showed that the expression level of IL-4 mRNA was significantly higher in splenocytes prepared from the DEX group at D7, compared with the VEH group. Importantly, the mRNA expression level of T-bet, a key transcription factor for immune cells, was greatly decreased in the spleen of the DEX group at D7, compared with the VEH group. In conclusion, prenatal dexamethasone exposure shows the greater impact on immune responses of their male offspring in early life.

keywords —— glucocorticoid; immune programming; offspring; prenatal exposure; spleen

© 2017 Tohoku University Medical Press

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Tohoku J. Exp. Med., 2017, 241, 225-237

Correspondence: Hong-Ren Yu, M.D., Ph.D., Department of Pediatrics, Chang Gung Memorial Hospital-Kaohsiung Medical Center, #123, Ta-Pei Road, Niao-Sung district, Kaohsiung, 83301, Taiwan.

e-mail: yuu2004taiwan@yahoo.com.tw