Lack of effect of metyrapone and exogenous cortisol on early porcine conceptus development

Abstract

A study was conducted to evaluate the influence of maternal cortisol on early conceptus development in pigs (Sus scrofa). The corticosteroid synthesis inhibitor metyrapone was injected daily during days 14-19 of pregnancy, without (n = 6) and with commensurate administration of cortisol (n = 6). Blood samples were taken via an indwelling jugular catheter on days 14 and 18, and conceptuses were harvested during surgery on day 20. Compared with vehicle-injected control dams (n = 7) plasma cortisol and aldosterone concentrations were decreased (P < 0.01) by 52 and 29%, respectively, by metyrapone treatment. Cortisol administration reversed decreases in plasma cortisol by day 18. There were no treatment-associated effects on conceptus survival or size. Nor were there treatment-associated effects on allantoic fluid volume or content. Trophodermal glucocorticoid receptor (GR) mRNA expression decreased by 34% (P < 0.05) in metyrapone-treated pigs, and was not further influenced by concomitant administration of cortisol, thereby suggesting an influence of aldosterone on GR mRNA expression. Also, when all pigs were considered, there were treatment-independent second-order polynomial regressions (P < 0.05) between maternal plasma cortisol concentrations and embryonic weight, allantoic size and allantoic glucose concentrations, and between plasma aldosterone concentrations and trophodermal GR mRNA expression. Such biphasic corticosteroid concentration versus tissue parameter curves are noteworthy, but difficult to interpret validly. They may suggest that an appropriate corticosteroid environment is necessary for optimal porcine embryonic development during this stage of gestation, but cannot overshadow the absence of treatment effects on the porcine embryonic measures evaluated.

Developmental toxicity and programming alterations of multiple organs in offspring induced by medication during pregnancy

“…A study has found that the use of dexamethasone during pregnancy can significantly reduce the level of cortisol in neonatal cord blood; the animal experiment has confirmed that PDE can inhibit maternal adrenal steroid synthesis, which decreases the glucocorticoid level in the mother and the level of maternal-derived glucocorticoids in the fetus 120 . In addition, prenatal metyrapone exposure can also inhibit maternal steroid synthesis and thus reduce fetal maternal-derived glucocorticoid level with decreased placental glucocorticoid receptor (GR) expression 121 .…”