Effects of Prenatal Dexamethasone on the Rat Pituitary Gland and Gonadotropic Cells in Female Offspring

Abstract

Glucocorticoids have a strong influence on growth and maturation of fetal organ systems, but overexposure to exogenous glucocorticoids may retard fetal growth and alter developmental processes in sensitive tissues. The aim of this study was to specifically determine whether prenatal exposure to dexamethasone (Dx) altered normal development and function of pituitary gonadotropic cells in neonatal, infant and peripubertal female offspring. On day 16 of pregnancy, rat dams received 1.0 mg Dx/kg body weight (BW) s.c., followed by 0.5 mg Dx/kg BW on days 17 and 18 of gestation. Control gravid females received the same volume of saline. Female offspring were sacrificed on days 5, 16 and 38 after delivery. The volume of the pituitary gland estimated using Cavalieri's principle was significantly reduced (p < 0.05). Using a fractionator-physical disector method, we found reduced total numbers of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) cells (p < 0.05), accompanied by a decrease (p < 0.05) in serum concentrations of FSH and LH, while the relative intensity of FSH and LH immunofluorescence remained unchanged in neonatal, infant and peripubertal female offspring prenatally exposed to Dx. The data document that overexposure to Dx during fetal development evokes developmental programming of the female reproductive system at the pituitary cellular level, which may be associated with impaired reproductive function.

The changes in semen quality, arginase activity and nitric oxide level in dexamethasone‐treated rams

“…Dexamethasone inhibits serum luteinising hormone (LH) (Ristić et al, 2016) and testosterone (Sadeghzadeh, Mehranjani, & Mahmoodi, 2019), which affect the testicular endocrine function; therefore, it affects sperm transportation, sperm metabolism and sperm maturation in the epididymis (Tsantarliotou et al, 2002).…”

Adverse effect of dexamethasone on development of the fetal rat ovary

“…These data document the programming effect of Dx at the level of the ovary. Clear programming effects of Dx were also detected in the hypothalamus and pituitary gland . Dx‐induced changes at all three levels of the hypothalamo–pituitary–gonadal axis may contribute seriously to impaired reproductive function during adulthood.…”

“…Expression of proliferating cell nuclear antigen (PCNA) and caspase‐3 in the fetal ovaries was investigated using immunohistochemical methods . After deparaffinization and rehydratation, two‐micrometer‐thick serial sections were pretreated with citrate buffer for antigen retrieval according to standard protocols.…”

“…Namely, exposure to Dx during the most vulnerable period in pituitary development markedly reduced gonadotropic cell number, which partly contributed to diminished volume of the entire gland in rat fetuses . Changes established during fetal development are long lasting and persist postnatally throughout neonatal, infant, and peripubertal periods . Prenatal exposure to Dx also decreased the number of ovarian primordial, primary, and secondary follicles in neonatal offspring , which indicates reduced reproductive potential for each female.…”

Stress, Sex, and Sugar: Glucocorticoids and Sex-Steroid Crosstalk in the Sex-Specific Misprogramming of Metabolism

“…Unfortunately, few studies have assessed circulating sex steroids in female offspring following developmental overexposure to GCs. One study showed that maternal stress in guinea pigs increased T levels in female offspring during adulthood [ 212 ], whereas prenatal DEX led to reduced circulating follicle-stimulating hormone and luteinizing hormone in peripubertal rats [ 213 ] and lower serum E2 in adult female offspring [ 214 ]. The most consistent results reported in female offspring were alterations in the onset of puberty and variations in the length of estrus stages [ 215-220 ] as well as decreased numbers of healthy primordial follicles [ 221 , 222 ], likely due to the proapoptotic action of DEX reported on human and rat fetal ovaries [ 223 , 224 ].…”