Sexually dimorphic impact of prenatal hyperandrogenism on offspring growth trajectory in sheep.

In a translationally relevant ovine model of gestational hyperandrogenism we have previously reported cardiometabolic disruption in female offspring (males were not extensively studied). We hypothesized that gestational hyperandrogenism would lead to sex-specific disruption in offspring's growth, cytokine and metabolic milieu, potential mediators of cardiometabolic disease (CMD). 100 mg Testosterone propionate (T) or vehicle (C) was administered intramuscularly twice weekly between gestational days (GD) 30-90.

Early- to mid-gestational testosterone excess leads to adverse cardiac outcomes in postpartum sheep.

Cardiovascular dysfunctions complicate 10-20% of pregnancies, increasing the risk for postpartum mortality. Various gestational insults, including preeclampsia are reported to be associated with adverse maternal cardiovascular outcomes. One such insult, gestational hyperandrogenism increases the risk for preeclampsia and other gestational morbidities but its impact on postpartum maternal health is not well known.

Comparative lipidome study of maternal plasma, milk, and lamb plasma in sheep.

Lipids play a critical role in neonate development and breastmilk is the newborn's major source of lipids. Milk lipids directly influence the neonate plasma lipid profile. The milk lipidome is dynamic, influenced by maternal factors and related to the maternal plasma lipidome.

Developmental programming: adverse sexually dimorphic transcriptional programming of gestational testosterone excess in cardiac left ventricle of fetal sheep.

Adverse in-utero insults during fetal life alters offspring's developmental trajectory, including that of the cardiovascular system. Gestational hyperandrogenism is once such adverse in-utero insult. Gestational testosterone (T)-treatment, an environment of gestational hyperandrogenism, manifests as hypertension and pathological left ventricular (LV) remodeling in adult ovine offspring.

Evaluation of the Cardiometabolic Disorders after Spinal Cord Injury in Mice.

Changes in cardiometabolic functions contribute to increased morbidity and mortality after chronic spinal cord injury. Despite many advancements in discovering SCI-induced pathologies, the cardiometabolic risks and divergences in severity-related responses have yet to be elucidated. Here, we examined the effects of SCI severity on functional recovery and cardiometabolic functions following moderate (50 kdyn) and severe (75 kdyn) contusions in the thoracic-8 (T8) vertebrae in mice using imaging, morphometric, and molecular analyses.

Sexual dimorphism in testosterone programming of cardiomyocyte development in sheep.

Perturbed in utero hormone milieu leads to intrauterine growth retardation (IUGR), a known risk factor for left ventricular (LV) dysfunction later in life. Gestational testosterone (T) excess predisposes offspring to IUGR and leads to LV myocardial disarray and hypertension in adult females. However, the early impact of T excess on LV programming and if it is female specific is unknown.

A Review of Maternal Nutrition during Pregnancy and Impact on the Offspring through Development: Evidence from Animal Models of Over- and Undernutrition.

Similarities in offspring phenotype due to maternal under- or over-nutrition during gestation have been observed in studies conducted at University of Wyoming. In these studies, ewes were either nutrient-restricted (NR) from early to mid-gestation, or fed an obesogenic diet (MO) from preconception through term. Offspring necropsies occurred at mid-gestation, late-gestation, and after parturition.

Maternal obesity in sheep impairs foetal hepatic mitochondrial respiratory chain capacity.

Background: Changes in the nutritional environment in utero induced by maternal obesity (MO) lead to foetal metabolic dysfunction predisposing offspring to later-life metabolic diseases. Since mitochondria play a crucial role in hepatic metabolism and function, we hypothesized that MO prior to conception and throughout pregnancy programmes foetal sheep liver mitochondrial phenotype.

Material And Methods: Ewes ate an obesogenic diet (150% requirements; MO), or 100% requirements (CTR), from 60 days prior to conception.

Long-term neural regeneration following injury to the peroneal branch of the sciatic nerve in sheep.

Peripheral nerves (PNs) are frequently injured as a result of trauma or disease. Development of therapies to regenerate PNs requires the use of animal models, typically beginning in rodents and progressing to larger species. There are several large animal models of PN regeneration that each has their benefits and drawbacks.

A heretical view: rather than a solely placental protective function, placental 11β hydroxysteroid dehydrogenase 2 also provides substrate for fetal peripheral cortisol synthesis in obese pregnant ewes.

Exposure to glucocorticoid levels higher than appropriate for current developmental stages induces offspring metabolic dysfunction. Overfed/obese (OB) ewes and their fetuses display elevated blood cortisol, while fetal Adrenocorticotropic hormone (ACTH) remains unchanged. We hypothesized that OB pregnancies would show increased placental 11β hydroxysteroid dehydrogenase 2 (11β-HSD2) that converts maternal cortisol to fetal cortisone as it crosses the placenta and increased 11β-HSD system components responsible for peripheral tissue cortisol production, providing a mechanism for ACTH-independent increase in circulating fetal cortisol.

A Long-Term Pilot Study on Sex and Spinal Cord Injury Shows Sexual Dimorphism in Functional Recovery and Cardio-Metabolic Responses.

More than a quarter of a million individuals in the US live with spinal cord injury (SCI). SCI disrupts neural circuitry to vital organs in the body. Despite severe incidences of long-term peripheral complications from SCI, the cardio-metabolic consequences and divergences in sex-related responses are not well described.

Toluidine Blue Staining of Resin-Embedded Sections for Evaluation of Peripheral Nerve Morphology.

Peripheral nerves extend throughout the body, innervating target tissues with motor or sensory axons. Due to widespread distribution, peripheral nerves are frequently damaged because of trauma or disease. As methods and strategies have been developed to assess peripheral nerve injury in animal models, function and regeneration, analyzing the morphometry of the peripheral nerve has become an essential terminal outcome measurement.

Rapid Communication: Reduced maternal nutrition during early- to mid-gestation elevates newborn lamb plasma cortisol concentrations and eliminates the neonatal leptin surge.

Human epidemiological and animal studies show that maternal nutrient reduction (MNR) and maternal overnutrition/obesity (MO) alter fetal growth and development, predisposing offspring (F1) to endocrine and appetite dysregulation. Compared to F1 of control-fed ewes, F1 of MO ewes display hypercortisolemia at birth and fail to exhibit the neonatal leptin surge implicated in lifelong appetite regulation. Here, we determined if MNR also elevates newborn lamb plasma cortisol and eliminates the neonatal leptin surge.

Maternal obesity in the ewe increases cardiac ventricular expression of glucocorticoid receptors, proinflammatory cytokines and fibrosis in adult male offspring.

Obesity during human pregnancy predisposes offspring to obesity and cardiovascular disease in postnatal life. In a sheep model of maternal overnutrition/obesity we have previously reported myocardial inflammation and fibrosis, as well as cardiac dysfunction in late term fetuses, in association with chronically elevated blood cortisol. Significant research has suggested a link between elevated glucocorticoid exposure in utero and hypertension and cardiovascular disease postnatally.