Endocrine Abstracts

Background: Previous studies have linked a low protein maternal diet with hypertension in adult offspring, and have suggested that impaired kidney development may be an important predisposing factor. This study aims to identify the molecular and structural changes that explain the decline in function.Methods: Pregnant ewes were fed either a control diet providing adequate dietary protein (control protein (CP); n=15), or a low protein diet during e...

Placental 11β-hydroxysteroid dehydrogenase-2 (11β-HSD2) rapidly converts glucocorticoids to inactive metabolites, thus protecting the developing fetus from high maternal glucocorticoids. Genetic deficiency or inhibition of 11β-HSD2 associates with fetal growth restriction, low birth weight, and cardiometabolic disease in adulthood. Similar ‘programming’ effects are seen with maternal malnutrition or stress; these challenges associate with reduced place...

Loss-of-function mutations in FGF8 in humans have been associated with Kallmann syndrome (KS), which is characterised by the combination of hypogonadotrophic hypogonadism with anosmia, suggesting that FGF8 is critical for GnRH neuronal development. Interestingly, hypomorphic Fgf8 mutant mice demonstrate poor telencephalic development with deletions of midbrain tissue, absence of olfactory bulbs and optic chiasm, and holoprosencephaly (HPE) with an abnormal corpus...

Glucocorticoid levels rise dramatically in late gestation in mammals and are essential for organ maturation in preparation for birth. They are widely used clinically to mature the lungs of premature infants and hypomorphic GR mice die neonatally due to severe lung atelectasis. Here, we describe fetal lethality in GR null (GR−/−) mice with 51% loss at E17.5 (P<0.05) that could be due to impaired cardiac development. Histology showed reduced hea...

Prenatal glucocorticoid overexposure is a key risk factor for susceptibility to neuropsychiatric disorders in adult life. Fetal exposure to glucocorticoids is regulated by 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) an enzyme which inactivates glucocorticoids and is highly expressed in the placenta and fetus. Previous work has established that 11β-HSD2−/− offspring generated by heterozygous matings exhibit altered placental developm...

Exposure to a range of environmental endocrine disrupting chemicals is associated with birth defects in several species. High levels of oestrogen, or compounds acting as oestrogen mimics (such as alkyl phenols and pesticides) can alter gene expression and cause sex reversal in fish. In the current study, we use the versatile Zebrafish (Danio rerio) to examine the effect of embryonic exposure to 17β-estradiol (E2) on the development of brain asymmetry and...

Introduction: Several biomarkers are elevated in late pregnancy in women with preeclampsia (PET), but none have been sensitive or specific enough to be used routinely in early pregnancy to predict the condition. We measured plasma levels of the anti-angiogenic peptides FMS-like tyrosine kinase 1 (sFLT-1), soluble endoglin (sENG), placental growth-factor (PGF), and an array of cytokines and adhesion molecules in early and mid pregnancy to assess their ability to predict PET.</p...

The plasma membrane thyroid hormone (TH) transporter, MCT8, is present in the human placenta from early gestation and is postulated to participate in transplacental transfer of TH. In vitro, MCT8 overexpression decreases the survival of human cytotrophoblast in a TH-independent manner.Objective: To examine the role of Mct8 in fetoplacental growth using the Mct8 knockout (ko) mouse model.Methods: Heterozygous females were mat...