The impact of the periconceptional environment (in vivo and ex vivo) on feto-placental development in the sheep.

A range of epidemiological, clinical and experimental studies have demonstrated that exposure of an embryo to a suboptimal environment in vivo or ex vivo during early embryo development is associated with altered development of cardiovascular, neuroendocrine and metabolic disorders in adult life. A number of perturbations during early embryo development result in developmental adaptations by the embryo to ensure immediate survival, whilst programming the embryo for altered fetal and placental development, resulting in the eventual onset of adult disease. It has been previously shown that maternal nutrient restriction during the periconceptional period results in a hyperactivation of the pituitary - adrenal axis and increased mean arterial blood pressure in twin but not singleton pregnancies. It was therefore the first aim of this thesis to interrogate the impact of maternal undernutrition during the periconceptional period (defined as from at least 45 days prior until 7 days after conception) on fetal and placental development during early pregnancy at - day 55 of pregnancy, which coincides with the period of maximal placental growth. In Chapter 2, it has been demonstrated that there are important relationships between maternal weight gain during the periconceptional period and feto-placental growth during the first - 55 days of pregnancy and that periconceptional undernutrition has a differential effect on these relationships in singleton and twin pregnancies. In singleton pregnancies, periconceptional undernutrition disrupts the relationship between maternal weight gain during the periconceptional period and utero-placental growth and in twin pregnancies, periconceptional undernutrition results in the emergence of an inverse relationship between maternal weight gain during early pregnancy and uteroplacental growth and in a dependence of fetal growth on placental growth. (Chapter 2) In order to investigate the origins of the physiological adaptations that lead to the development of hyperactivation of the pituitary - adrenal axis and increased mean arterial blood pressure in late gestational fetuses after exposure as an embryo to periconceptional undernutrition, we investigated the development and steroidogenic capacity of the fetal adrenal gland and development of the fetal heart and kidney at - 55 days gestation (Chapter 3 and 4). The relative weight of the fetal adrenal and adrenal IGF-1, IGF-1 R, IGF-2, IGF-2R and CYP 17 mRNA expression were lower in twin compared to singleton fetuses. There was evidence that in control singletons, IGF-2R expression plays an important role in the regulation of adrenal growth and CYP 17 mRNA expression during early pregnancy. In control twins, however, whilst there was a significant positive relationship between adrenal CYP 17 and IGF-2 mRNA expression, adrenal weight was directly related to the level of adrenal IGF-1 mRNA expression. There was no effect of periconceptional undernutrition on the level of expression of any of the placental or adrenal genes in the study. In PCUN ewes, carrying singletons, however, there was a loss of the relationships between either adrenal IGF-2, IGF-2R and IGF-1 mRNA expression and adrenal growth and CYP 17 expression which were present in control singletons. Similarly in ewes carrying twins, maternal undernutrition during the periconceptional period resulted in the loss of the relationships between adrenal growth and IGF-1 expression and between _ adrenal CYP 17 and IGF-2 expression which were present in control twin fetuses. Whilst there was no effect of fetal number on fetal heart growth at - d55 in twin fetuses, there was a direct relationship between relative fetal heart and adrenal weights, which was present in both the PCUN and control groups. There was also a significant inverse relationship between maternal weight at conception and relative fetal heart weight in PCUN twin, but not PCUN singleton or control fetuses (Chapter 3). In control pregnancies maternal weight gain during the periconceptional period is inversely related to the relative weight of the fetal kidney at -55d pregnancy. In this group, relative kidney weight was also directly related to renal IGF-1 mRNA expression. In control twins maternal weight gain was inversely related to fetal kidney weight and this effect was ablated when the effects of maternal cortisol was controlled for in the analysis. In the PCUN group, whilst there was an inverse relationship between maternal weight gain during the periconceptional period and relative kidney weight, it was not possible to separate the independent effects of maternal weight loss during the periconceptional period and the subsequent weight gain during the period of refeeding. Renal IGF-1 mRNA expression was higher and renal lGF-1 R and 2R expression were lower in twin fetuses compared to singletons. After exposure to PCUN, renal IGF-1 expression was also higher than in control pregnancies independent of the fetal number (Chapter 4). Superovulation, artificial insemination, embryo transfer and in vitro embryo culture are used in a range of assisted reproductive technologies, and it has been demonstrated that varying the composition of the culture media can result in a change in pre and postnatal development. Culture of sheep embryos in media containing serum is associated with fetal overgrowth which is phenotypic of the Large Offspring Syndrome. It is not known how the combination of superovulation, artificial insemination and embryo transfer alone impacts fetoplacental development in late gestation of the sheep. There have been no studies, however, examining the differential impact of superovulation, artificial insemination and embryo transfer with or without in vitro embryo culture in the absence or presence of human serum on feto-placental development in Singleton and twin pregnancies (Chapter 5). I have therefore tested the hypothesis that superovulation, artificial insemination and embryo transfer with or without in vitro embryo culture in the presence or absence of human serum differentially alters the growth of the placenta, fetus and fetal organs during late gestation when compared to naturally conceived controls and that these effects are different in singleton and twin pregnancies. The fetal weight, CRL and abdominal circumference were significantly larger in IVCHS singleton fetuses. A novel finding in this study was lower fetal weights of twin fetuses in the ET and IVCNS groups compared to NM control twin fetuses. In addition, placental weights were lighter in twin fetuses in the ET, IVCNS and IVCHS treatment groups and this is partially due to a failure to initiate compensatory growth of placentomes in twin pregnancies (Chapter 5). The results of this thesis therefore highlight the complex interactions between the periconceptional environment (in vivo or ex vivo) and embryo or fetal number on the programming fetal and placental development. Maternal undernutrition during the periconceptional period and superovulation, artificial insemination and embryo transfer with or without in vitro culture in the absence or presence of serum alters fetal development, and I have demonstrated that these changes in fetal growth can be explained by changes in placental growth trajectory. Furthermore, a novel finding of this study is that perturbations of the periconceptional environment affect feto-placental development differently in singleton and twin pregnancies.Thesis (Ph.D.) -- University of Adelaide, School of Molecular and Biomedical Science, 200

Oral History Transcript | Interview with Warren Luther, June 30, 1999

https://digitalcommons.risd.edu/archives_oralhistories_transcripts/1035/thumbnail.jp

Differential effects of exposure to maternal obesity or maternal weight loss during the periconceptional period in the sheep on insulin signalling molecules in skeletal muscle of the offspring at 4 months of age.

Exposure to maternal obesity before and/or throughout pregnancy may increase the risk of obesity and insulin resistance in the offspring in childhood and adult life, therefore, resulting in its transmission into subsequent generations. We have previously shown that exposure to maternal obesity around the time of conception alone resulted in increased adiposity in female lambs. Changes in the abundance of insulin signalling molecules in skeletal muscle and adipose tissue precede the development of insulin resistance and type 2 diabetes. It is not clear, however, whether exposure to maternal obesity results in insulin resistance in her offspring as a consequence of the impact of increased adiposity on skeletal muscle or as a consequence of the programming of specific changes in the abundance of insulin signalling molecules in this tissue. We have used an embryo transfer model in the sheep to investigate the effects of exposure to either maternal obesity or to weight loss in normal and obese mothers preceding and for one week after conception on the expression and abundance of insulin signalling molecules in muscle in the offspring. We found that exposure to maternal obesity resulted in lower muscle GLUT-4 and Ser 9 phospho-GSK3α and higher muscle GSK3α abundance in lambs when compared to lambs conceived in normally nourished ewes. Exposure to maternal weight loss in normal or obese mothers, however, resulted in lower muscle IRS1, PI3K, p110β, aPKCζ, Thr 642 phospho-AS160 and GLUT-4 abundance in the offspring. In conclusion, maternal obesity or weight loss around conception have each programmed specific changes on subsets of molecules in the insulin signalling, glucose transport and glycogen synthesis pathways in offspring. There is a need for a stronger evidence base to ensure that weight loss regimes in obese women seeking to become pregnant minimize the metabolic costs for the next generation

Impact of periconceptional and preimplantation undernutrition on factors regulating myogenesis and protein synthesis in muscle of singleton and twin fetal sheep.

In this study, we determined the effect of maternal undernutrition in the periconceptional (PCUN: ~80 days before to 6 days after conception) and preimplantation (PIUN: 0-6 days after conception) periods on the mRNA and protein abundance of key factors regulating myogenesis and protein synthesis, and on the relationship between the abundance of these factors and specific microRNA expression in the quadriceps muscle of singleton and twin fetal sheep at 135-138 days of gestation. PCUN and PIUN resulted in a decrease in the protein abundance of MYF5, a factor which determines the myogenic lineage, in singletons and twins. Interestingly, there was a concomitant increase in insulin-like growth factor-1 mRNA expression, a decrease in the protein abundance of the myogenic inhibitor, myostatin (MSTN), and an increase in the mRNA and protein abundance of the MSTN inhibitor, follistatin (FST), in the PCUN and PIUN groups in both singletons and twins. These promyogenic changes may compensate for the decrease in MYF5 protein abundance evoked by early embryonic undernutrition. PCUN and PIUN also increased the protein abundance of phosphorylated eukaryotic translation initiation factor binding protein 1 (EIF4EBP1; T70 and S65) in fetal muscle in singletons and twins. There was a significant inverse relationship between the expression of miR-30a-5p, miR-30d-5p, miR-27b-3p, miR106b-5p, and miR-376b and the protein abundance of mechanistic target of rapamycin (MTOR), FST, or MYF5 in singletons or twins. In particular, the expression of miR-30a-5p was increased and MYF5 protein abundance was decreased, in PCUN and PIUN twins supporting the conclusion that the impact of PCUN and PIUN is predominantly on the embryo

Being Better Americans and Doing It for Them: The Peace Corps in Micronesia

Conference paper for the 9th Annual Pacific Islands Studies Conference, "History of the U. S. Trust Territory of the Pacific Islands," UH-Manoa, 1984

Interests and Dependencies: The Pacific After Cook

Conference paper for the 3rd Annual Pacific Islands Studies Conference, "Captain Cook and the Pacific Islands," 1978, UH-Mano

From Atoll to Federal Agency: The Politics of Feeding People

Conference paper for the 4th Annual Pacific Islands Studies Conference, "The Emerging Pacific Island States," 1979, UH-Mano

The Contribution of Geriatric Educators to Public Policy

Abstract Despite the current pressure to reduce state and federal spending, policymakers must find ways to address the challenges of a growing population of older adults with complex health care problems. There is an increased need for the health professions workforce to have collaborative care skills and geriatric clinical competencies. Therefore, programs like the Geriatric Workforce Enhancement Program (GWEP) and the Geriatric Academic Career Awards (GACA) are important in strengthening the workforce and supporting policy development that addresses increased demands on the health care system. In 2019, the Bureau of Health Professions, under the Health Resources and Services Administration, provided 48 GWEP awards and 26 GACA awards in 37 states and 2 territories. These programs play an important advocacy role to improve on and expand geriatric education. This symposium provides an overview of these programs and their role in advancing geriatric care and in shaping policy.</jats:p