Exposure to dexamethasone reduces pituitary volume and gonadotropic cell number in rat fetuses

Ristić, Nataša; Nestorović, Nataša; Manojlović‐Stojanoski, Milica; Medigović, Ivana; Trifunović, Svetlana; Šošić‐Jurjević, Branka; Milošević, Verica

doi:10.1016/j.acthis.2014.04.003

Cited by 4 publications

(5 citation statements)

References 31 publications

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“…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.…”

Section: Discussionmentioning

confidence: 97%

“…Our recent results, obtained by exploiting a rat model, indicate that prenatal exposure to Dx leads to novel developmental programming of the reproductive system at the level of the pituitary gland and ovary. 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 .…”

Section: Introductionmentioning

confidence: 99%

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Adverse effect of dexamethasone on development of the fetal rat ovary

Ristić

Nestorović

Manojlović‐Stojanoski

et al. 2018

Fundamemntal Clinical Pharma

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Dexamethasone (Dx) is often used in obstetric practice to promote fetal lung maturation and to prevent respiratory distress syndrome when the risk of preterm delivery persists. This therapy enables survival of the newborn, but also is associated with deleterious effects on the offspring, such as reproductive disorders. The aim of this study was to determine specifically whether prenatal exposure to Dx disturbs the physiological balance between proliferation and apoptosis of germinative cells (GC) in the ovary of 19- and 21-day-old fetuses and thus induces developmental programming of the female reproductive system. Pregnant Wistar rats (n = 10/group), separated into control (vehicle) and Dx-treated (0.5 mg/kg body mass) groups, received injections on gestational days 16, 17, and 18. Exposure to Dx lowered the volume of the fetal ovary by 30% (P < 0.05) in 21-day-old fetuses, as well as the total number of GC in the ovary by 21% (P < 0.05). When compared to the controls, in Dx-exposed fetuses, the total number of PCNA-positive GC was 27% lower at 19 days and 71% lower at 21 days old (P < 0.05), while total numbers of caspase-3-positive GC were 2.3-fold and 34% higher, respectively (P < 0.05). Our results demonstrate that prenatal exposure to Dx diminished proliferation but increased the rate of germinative cell apoptosis, with consequently reduced total germinative cell number and ovary volume. Impairment of fetal oogenesis and fewer GC in the fetal ovary compromise the oogonial stock and thus may constitute a risk of female fertility.

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Section: Discussionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

Adverse effect of dexamethasone on development of the fetal rat ovary

Ristić

Nestorović

Manojlović‐Stojanoski

et al. 2018

Fundamemntal Clinical Pharma

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“…Three-micrometer-thick serial sections of the pituitaries were stained with immunohistochemical or immunofluorescence (IFC) methods [Miler et al, 2014;Ristić et al, 2014]. Briefly, after initial tissue deparaffinization, endogenous peroxidase activity was blocked by incubation with 0.3% hydrogen peroxide in methanol for 15 min.…”

Section: Immunohistochemical and Immunofluorescence Analysesmentioning

confidence: 99%

“…Design-based stereology is considered the gold standard for estimating the total number of cells [Manojlović-Stojanoski et al, 2010;Ristić et al, 2014] or morphological structure in organs, such as follicles in the ovary [Myers et al, 2004;Charlston et al, 2007;Ristić et al, 2008;Medigović et al, 2012] or nephrons in the kidney [Cullen-McEwan et al, 2012]. Estimation of the total number of gonadotrophic cells in the pituitary gland in combination with another histochemical/stereological and biochemical technique may provide evidence whether the prenatal exposure to Dx induces developmental programming of the hypothalamo-pituitary-gonadal axis at the pituitary level in the neonatal, infant and peripubertal female offspring.…”

Section: Effects Of Prenatal Dexamethasone On the Rat Pituitary Glandmentioning

confidence: 99%

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

Ristić

Severs

Nestorović

et al. 2016

Cells Tissues Organs

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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.

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“…Ristic et al,(24) reported that over exposure to GCs during the fetal period induce changes in developmental processes in various fetal tissues. Belzk et al,…”

mentioning

confidence: 99%

Effects of the prednisolone and hydrocortisone on the body weight of the pregnant rats and their embryo in the different stages of pregnancy

Dhahir latif Al-Hussainy,

Kareem Khalaf

2017

Qad Med J

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The aim of the study was to investigate the effects of prednisolone and hydrocortisone on the body weight of the pregnant rats and their embryos after treatment with the drugs during pregnancy.Materials and Methods: Thirty six adult female pregnant rats were randomly divided into three groups: Grop-1: control group C. (n = 12) received Distilled water 1 ml /kg b.w./day/intramuscularly for 14 days. Group-2: first treatment T1. (n=12) treated with prednisolone 4mg/kg b.w/day/intramuscularly for 14 days . Group-3: second treatment T2.(n=12) treated with hydrocortisone 40mg/kg b.w/day/ intramuscularly for 14 days.The body weight of the pregnant rats and their embryo detected at the day 15th and 20th of the gestation (developmental stage of rat embryo=E). At the detected period for taking the body weight of the pregnant rats and six animals from each group were sacrificed and taken the body weight of embryo with and without placenta.Results: the results showed that prednisolone decrease the body weight of the pregnant rats and its embryo more than hydrocortisone, and may cause absorption for percentage of embryo.Conclusion: prednisolone and hydrocortisone causes low body weight in the pregnant rats and its embryo when used for 14 days intramuscularly.

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Exposure to dexamethasone reduces pituitary volume and gonadotropic cell number in rat fetuses

Cited by 4 publications

References 31 publications

Adverse effect of dexamethasone on development of the fetal rat ovary

Adverse effect of dexamethasone on development of the fetal rat ovary

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

Effects of the prednisolone and hydrocortisone on the body weight of the pregnant rats and their embryo in the different stages of pregnancy

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