The effects of dexamethasone administered during pregnancy on the postpartum spiny mouse ovary (original) (raw)
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Adverse effect of dexamethasone on development of the fetal rat ovary
Fundamental & Clinical Pharmacology
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 programing 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 day 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 for female fertility.
Biology of Reproduction, 2001
The effect of dexamethasone on LH-induced synthesis of steroidogenic acute regulatory (StAR) protein was studied in a serum-free culture of preovulatory follicles. StAR protein is a steroidogenic tissue-specific, hormone-induced, rapidly synthesized protein previously shown to be involved in the acute regulation of steroidogenesis, probably by promoting the transfer of cholesterol to the inner mitochondrial membrane and the cytochrome P450 side-chain cleavage (P450 scc) enzyme. Treatment of preovulatory follicles dissected from ovaries of cyclic adult rats on the morning of proestrus with LH for 24 h resulted in a dose-dependent increase in the level of StAR protein that reached a maximum at 10 ng LH/ml. This increase was associated with an increase in progesterone production. Treatment of the follicles with increasing concentrations (1-1000 ng/ml) of dexamethasone suppressed LH (10 ng/ml)-induced StAR protein levels and progesterone production in a dose-dependent manner. The amount of P450 scc was not affected by this dexamethasone treatment, indicating that the loss of steroidogenic capacity was not a result of inhibition of P450 scc. Dexamethasone also decreased StAR protein levels and progesterone production induced by the adenylate cyclase activator forskolin (10 Ϫ5 M) or a cAMP analogue 8-Br-cAMP (0.5 mM). The effects of dexamethasone on 8-Br-cAMP-induced StAR protein levels and progesterone production were blocked by cotreatment of the follicles with glucocorticoid receptor antagonist RU-486. These results demonstrate that dexamethasone inhibits the LH-induced StAR protein levels and that the effects of dexamethasone are mediated by the glucocorticoid receptor.
International Journal of Morphology, 2008
The present study had the objective of obtaining information about fertility in rats treated with dexamethasone for 10 and 15 days consecutively, to polycystic ovaries, induced by constant illumination. It was used 40 albino rats (Rattus norvegicus albinus), aged 90 days, form the lineage Wistar, which were split, randomly, in four groups, each constituted of 10 animals, namely: Group I-rats kept in a clear/dark cycle for 12/12 hours, and after 100 days submitted to fertility evaluation (control); Group II-rats kept under constant illumination during 100 days and then submitted to fertility evaluation; Group III-rats kept under constant illumination during 100 days, then treated with dexamethasone for 10 days and submitted to fertility evaluation; Group IV-rats kept under constant illumination during 100 days, then treated with dexamethasone for 15 days and submitted to fertility evaluation. The results showed that the number of implanted sites was 38(G1), 37(G2), 32(G3) and 06(G4). The reduction in group IV was due to the high mortality during the experiment, probably because of the prolonged treatment with dexamethasone. These sites presented similar histological aspects. The macroscopic analysis of the neonates haven't shown any indication of malformation. Also, abortion haven't been observed. The treatment with dexamethasone for 10 days in rats does not affect the fertility and the development of the lungs, liver and kidneys of neonates, while the administration during 15 days leads to a high maternal mortality.
Pregnancy and dexamethasone: Effects on morphometric parameters of gonadotropic cells in rats
Acta Histochemica, 2007
The effects of pregnancy and multiple dexamethasone (Dx) treatment on morphometric parameters of adenohypophyseal gonadotropic cells that produce follicle stimulating hormone (FSH) and luteinizing hormone (LH) were investigated in female Wistar rats. The rats in the experimental group received injections of 1.0, 0.5 and 0.5 mg Dx/kg b.w. on days 16-18 of pregnancy, while the control group received equal volumes of saline. There was also an age-matched adult virgin control group. The experimental and control animals were sacrificed 24 and 72 h after the last injection. Using the peroxidase-anti-peroxidase immunohistochemical labeling procedure, morphometric analyses showed that cell volume and volume density of FSH and LH cells on day 19 of pregnancy, as well as the number of LH cells, were significantly decreased compared to the virgin control values. On day 21 of gestation, the volume of FSH and LH cells remained smaller than in the virgin controls. Moreover, FSH and LH cell volume was significantly decreased 24 h after multiple Dx treatment in comparison with the pregnant controls. Thus, during the last days of pregnancy, the morphometric parameters of gonadotropic cells decreased in comparison with the control virgin rats, but Dx treatment of pregnant rats had an inhibitory influence on FSH and LH cell size only 24 h after the last dose.
Biochemical and Biophysical Research Communications, 2003
We have recently demonstrated that glucocorticoids protect against serum-deprivation, cAMP-, TNFa-, and p53-induced apoptosis in ovarian follicular cells involved in up-regulation of Bcl-2. We demonstrated that dexamethasone, which enhances steroidogenesis by up-regulation of the p450scc enzyme system, stimulates the MAPK cascade by phosphorylation of ERK1, ERK2 as well as by Akt phosphorylation within 1-5 min with no effect on p38 MAPK phosphorylation. Moreover, glucocorticoids enhance expression of connexin 43, formation of gap junctions, expression of cadherins, and formation of adherence junctions within 24 h of hormone stimulation of ovarian granulosa cells. It is suggested that the protective effects of glucocorticoids against apoptosis are mediated by both genomic and non-genomic mechanisms. Moreover, for the first time we show that protein phosphorylation, cell-cell contact, and intracellular communication are important mediators in glucocorticoid protection against apoptosis in ovarian follicular cells.
Reproductive Biology and Endocrinology, 2009
Background: Cystic ovarian disease is an important cause of infertility that affects bovine, ovine, caprine and porcine species and even human beings. Alterations in the ovarian micro-environment of females with follicular cysts could alter the normal processes of proliferation and programmed cell death in ovarian cells. Thus, our objective was to evaluate apoptosis and proliferation in ovarian cystic follicles in rats in order to investigate the cause of cystic follicle formation and persistence.
Effect of the denervation of porcine ovaries on dexamethasone-induced cyst formation
Acta Veterinaria Hungarica, 2013
Previously, we have shown that the activity of noradrenergic nerve fibres increased and the steroid content changed in porcine ovaries with dexamethasone-(DXM-) induced polycystic status. To better understand the role of the ovarian nerves in the formation of cystic status, the morphology and steroidogenic activity of the ovaries of DXM-treated gilts after denervation of the gonads were investigated in this study. Ovarian denervation was performed on day 3 of the first studied oestrous cycle and then, on days 7-21 of the cycle, DXM was administered. Following neurectomy and DXM treatment, cysts, medium-sized follicles and corpora lutea were not present, while the number of small-sized follicles increased. Denervation and DXM application led to a reduction in the number of dopamine-β-hydroxylase-and/or neuropeptide Y-immunoreactive nerve fibres. The concentrations of progesterone, androstenedione, testosterone and oestradiol-17β in the follicular fluid and/or in the wall of small-sized follicles of the experimental gilts were lower than in the controls. A similar result was demonstrated for P450scc, 3β-HSD and P450arom protein contents in the small follicles. Our data showed that DXM was not able to stimulate the formation of cysts in denervated porcine ovaries, indicating that the ovarian peripheral nerves might participate in the aetiopathogenesis of polycystic status.