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Adverse environmental conditions before birth are known to program adult metabolic and endocrine phenotype in several species. However, whether increments in fetal cortisol concentrations of the magnitude commonly seen in these conditions can cause developmental programming remains unknown. Thus, this study investigated the outcome of physiological increases in fetal cortisol concentrations on glucose-insulin dynamics and pituitary-adrenal function in adult sheep. Compared to saline treatment, intravenous fetal cortisol infusion for 5 days in late gestation did not affect birthweight but increased lamb body weight at 1-2 weeks after birth. Adult glucose dynamics, insulin sensitivity and insulin secretion were unaffected by prenatal cortisol overexposure, assessed by glucose tolerance tests, hyperinsulinaemic-euglycaemic clamps and acute insulin administration. In contrast, prenatal cortisol infusion induced adrenal hypo-responsiveness in adulthood with significantly reduced cortisol responses to insulin-induced hypoglycaemia and exogenous adrenocorticotropic hormone (ACTH) administration relative to saline treatment. The area of adrenal cortex expressed as a percentage of the total cross-sectional area of the adult adrenal gland was also lower after prenatal cortisol than saline infusion. In adulthood, basal circulating ACTH but not cortisol concentrations were significantly higher in the cortisol than saline treated group. The results show that cortisol overexposure before birth programs pituitary-adrenal development with consequences for adult stress responses. Physiological variations in cortisol concentrations before birth may, therefore, have an important role in determining adult phenotypical diversity and adaptability to environmental challenges.

Extension-related magmatism with arc-like features was active in the South Apuseni Mountains, Romania during the Neogene and Quaternary. The current chronological framework is primarily restricted to K–Ar dates. We present here new laser ablation inductively coupled plasma mass spectrometry U–Pb zircon age data for 20 subvolcanic and volcanic rocks from eight different Cenozoic volcanic–intrusive complexes and from Jurassic and Cretaceous lava flows. Our results support magmatic ages between c. 14 and c. 7 Ma, with Uroi, an alkaline intrusion, occurring significantly later at c. 1.5 Ma. Revising the timeline for the South Apuseni Mountains palaeomagnetic rotations shows that most of the clockwise vertical-axis rotation of these mountains (54.4° ± 10.7°) took place between c. 14 and 11 Ma, the age interval when the majority of the magmas were emplaced. Xenocrystic zircon dates show differences in the age populations between individual volcanic–intrusive complexes. A Permo-Triassic population is almost ubiquitous, indicating that basement Permo-Triassic igneous rocks are more widespread than previously thought, or that they were significantly involved in the generation of Neogene magmas. However, other observed age populations, such as Triassic or Paleogene, have no clear correspondence in the known geological record, indicating the presence of a cryptic component interacting with Neogene magmas. Supplementary material: Full analytical details and age calculations for the U–Pb age data collected during this study, rock samples and separated zircon fraction descriptions and the palaeomagnetic and age databases are available at https://doi.org/10.6084/m9.figshare.c.6951429