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At least 1,081 records · Page 60Linked to original sources
PubMed2005

Late gestational exposure to the fungicide prochloraz delays the onset of parturition and causes reproductive malformations in male but not female rat offspring.

Prochloraz (PZ) is an imidazole fungicide that displays multiple endocrine activities. It inhibits steroid synthesis via P450 modulation and acts as an androgen receptor (AR) antagonist, but its effects on male sexual differentiation have not been described. The purpose of the current study was to expand in vitro observations and to determine whether PZ affected sexual differentiation. PZ effects on AR-mediated gene expression were tested using a cell line (MDA-kb2) containing endogenous AR and stably transfected with an MMTV-luc reporter. PZ concentrations greater than 1 microM caused a dose-dependent inhibition of dihydrotestosterone-induced gene expression. PZ also inhibited R1881 binding to the rat AR (IC50 approximately 60 microM). In vivo, pregnant rats received PZ by gavage from Gestational Day 14 to 18 at doses of 31.25, 62.5, 125, and 250 mg/kg of body weight per day. PZ delayed delivery in a dose-dependent manner and resulted in pup mortalities at the two highest doses. In male offspring, anogenital distance and body weight were slightly reduced at 3 days of age. Additionally, female-like areolas were observed at 13 days of age at frequencies of 31%, 43%, 41%, and 71% in the lowest-dose to highest-dose groups, respectively. Weights of androgen-dependent tissues showed dose-dependent reductions. Hypospadias and vaginal pouches were noted in all males treated with 250 mg/kg, whereas those defects were observed in 12.5% and 6.25%, respectively, of males treated with 125 mg/kg. Treatment did not affect age of preputial separation in animals without penile malformations. Despite severe malformations in males, no malformations were noted in females. Together, these results indicate that PZ alters sexual differentiation in an antiandrogenic manner.

Abnormalities, Drug-Induced↗
PubMed2006

Hypoxic inhibition of human myometrial contractions in vitro: implications for the regulation of parturition.

BACKGROUND: Insufficient tissue oxygenation is a likely contribution to weak, inco-ordinate human uterine contractile activity characteristic of prolonged, dysfunctional labour. However, the direct effects of hypoxia on human myometrial contractility has, surprisingly, not yet been detailed. Therefore, we report the influence of hypoxia on spontaneous and agonist-induced carbachol, prostaglandin (PGF2alpha), and oxytocin contractions of myometria from nonpregnant and pregnant women. MATERIALS AND METHODS: Uterine biopsies were obtained from pregnant women at term undergoing elective Caesarean section and nonpregnant women undergoing hysterectomy. Myometrial strips were equilibrated at 37 degrees C in normoxic physiological salt solution (95% air/5% CO(2)) and the influence of hypoxia (95% N(2)/5% CO(2)) on contractility was investigated. RESULTS: Hypoxia resulted in a significant reduction in spontaneous contractile function; nonpregnant tissue was less resistant to the deleterious effects of hypoxia. Agonist-induced contractions, while being more resistant to hypoxia than spontaneous contractions, were also significantly inhibited. In myometria of pregnant women the PGF2alpha- or oxytocin-induced contractility was more resistant to hypoxia than carbachol. Finally, the inhibitory actions of hypoxia were exacerbated with repeated oxytocin administration with a more severe effect on contractile integral than on initial phasic contraction amplitude. CONCLUSIONS: We detail, for the first time, the effects of hypoxia on contractility of human myometria from nonpregnant and pregnant women. Physiologically important uterotonic agents are more resistant to the effects of hypoxia than spontaneous contractions although repeated stimulation with oxytocin during hypoxia results in progressively less force. The results indicate that if significant hypoxia occurs in vivo then it is a likely contributory factor to the pathways underlying prolonged dysfunctional labour.

Adult↗
PubMed2006

The influence of dietary conjugated linoleic acid on blood serum and colostrum immunoglobulin G concentration in female goats before and after parturition.

The effects on blood serum and colostrum immunoglobulin G (IgG) levels from including conjugated linoleic acid (CLA) in the diet were evaluated in goats. In experiment 1, 20 goats were allotted into two groups; the CLA group received 20 g/kg of dry matter of CLA 60 and the control group received 0 g/kg of CLA 60, from the third month of gestation until partum. Blood samples were taken every 2 weeks from 1 day before CLA inclusion to partum. From partum until 96 hours, blood and colostrum samples were taken every 24 h. Before partum, IgG serum blood levels were 15.6 and 9.4 mg/ml (CLA and control, respectively); the time effect was statistically significant. After partum (96 h), the effect of CLA dietary inclusion was statistically significant.

Animal Feed↗
PubMed2006

A possible role for progesterone metabolites in human parturition.

There has been a recent resurgence of interest in the role of progesterone in the maintenance of human pregnancy and the onset of labour, following recent reports of its use to prevent preterm labour in high-risk patients. One possible mechanism by which progesterone might contribute to uterine quiescence is through the actions of its metabolites. This article provides a brief overview of progesterone in human pregnancy and an outline of progesterone metabolism in the various reproductive tract tissues as well as the evidence for actions of progesterone metabolites in pregnancy.

17-alpha-Hydroxyprogesterone↗