D. A. Redmer

Bio: D. A. Redmer is an academic researcher from University of Aberdeen. The author has contributed to research in topics: Placenta & Pregnancy. The author has an hindex of 7, co-authored 14 publications receiving 240 citations.

Growth and in-vitro metabolism of placental tissues of cows from day 100 to day 250 of gestation.

Abstract: Weight of placental tissues of cows increased exponentially from Day 100 to Day 250 of gestation, but at much slower relative and absolute rates than fetal weight. In addition, growth rate of fetal placental tissues was less than that of maternal placental tissues. Concentrations of DNA, RNA and protein, however, increased in fetal placental but not in maternal placental tissues. Fetal placental tissues therefore exhibited hyperplasia, which probably contributes to increased functional capacity of the placenta during late gestation. The rate of O2 uptake in vitro was greatest for maternal placental tissues, suggesting that the maternal portion of the placenta accounts for most of the large rate of placental O2 utilization in vivo. Compared with other placental tissues, rate of secretion of macromolecules by intercaruncular endometrium was high, but decreased from Day 100 to 250, suggesting that uterine glandular secretory activity may decrease as gestation advances. Rate of secretion of macromolecules also was high for intercotyledonary tissues and increased with day of gestation, suggesting a role for secretory products of chorioallantois in gravid uterine function.

Fetoplacental growth and vascular development in overnourished adolescent sheep at day 50, 90 and 130 of gestation.

Abstract: To establish the basis for altered placental development and function previously observed at late gestation, fetoplacental growth and placental vascular development were measured at three stages of gestation in a nutritional paradigm of compromised pregnancy. Singleton pregnancies to a single sire were established and thereafter adolescent ewes were offered an optimal control (C) or a high (H) dietary intake. At day 50, the H group had elevated maternal insulin and amniotic glucose, whereas mass of the fetus and placenta were unaltered. At day 90, the H group exhibited elevated maternal insulin, IGF1 and glucose; fetal weight and glucose concentrations in H were increased relative to C, but placental weight was independent of nutrition. By day 130, total placentome weight in the H group was reduced by 46% and was associated with lower fetal glucose and a 20% reduction in fetal weight. As pregnancy progressed from day 50 to 130, the parameters of vascular development in the maternal and fetal components of the placenta increased. In the fetal cotyledon, high dietary intakes were associated with impaired vascular development at day 50 and an increase in capillary number at day 90. At day 130, all vascular indices were independent of nutrition. Thus, high dietary intakes to promote rapid maternal growth influence capillary development in the fetal portion of the placenta during early to mid-pregnancy and may underlie the subsequent reduction in placental mass and hence fetal nutrient supply observed during the final third of gestation.

Angiogenic activity of maternal and fetal placental tissues of ewes throughout gestation.

Abstract: In Study 1, explants of caruncular and intercaruncular endometrium and fetal membrane were collected from ewes (5-6/day) on Days 11-13, 16-18 and 21-23 after mating and Days 10-12 after oestrus, and incubated for 24 h. Explant-conditioned media were evaluated for their effects on endothelial cell proliferation. Both caruncular and intercaruncular endometrium secreted factor(s) which stimulated endothelial cell proliferation, and which appeared to be greater than 100 x 10(3) Mr and heat-labile. In Study 2, conditioned media from explant incubations of caruncular and intercaruncular endometrium, cotyledon and intercotyledonary fetal membrane obtained from ewes (6-7/day) on Days 40, 65, 90, 115 and 140 after mating were evaluated for their effects on endothelial cell proliferation. Caruncular and intercaruncular endometrium and intercotyledonary fetal membrane secreted factor(s) which inhibited endothelial cell proliferation. Media from cotyledonary explants tended to stimulate endothelial cell proliferation on Day 115. Conditioned media from cotyledonary explants obtained from 3 additional ewes at Day 120 of gestation stimulated endothelial cell proliferation, and this activity also appeared to be greater than 100 x 10(3) Mr. Placental angiogenesis in ewes therefore appears to be modulated by both maternal and fetal placental tissues via stimulatory and inhibitory factors.

Angiogenic activity of placental tissues of cows.

Abstract: In Exp. 1, maternal (caruncle) and fetal (cotyledon) portions of the placenta as well as uterine endometrium were obtained from cows at mid-gestation and evaluated for angiogenic activity by placing tissue samples on chick chorioallantoic membranes (CAM). Only caruncular tissues exhibited angiogenic activity in the CAM assay. In Exp. 2, lyophilized homogenates of caruncular tissues obtained from cows at mid-gestation were evaluated for angiogenic activity on CAM and for their ability to stimulate mitosis of bovine aortic endothelial cells in vitro. Homogenates of caruncular tissues again were angiogenic on the CAM and also were mitogenic for endothelial cells. In Exp. 3, maternal (caruncle and endometrium) and fetal (cotyledon and fetal membrane) portions of the placenta were obtained from cows at mid-gestation and fine minces (explants) of each were cultured for 24 h. Explant-conditioned media were then tested for angiogenic activity by their abilities to stimulate mitosis and migration of bovine aortic endothelial cells in vitro. Conditioned media from caruncular explants, but not from explants of other tissues, exhibited both mitogenic and migration-stimulating activities. When pools of caruncular explant-conditioned media were fractionated by ultrafiltration, mitogenic activity was not present in fractions of Mr less than 10,000, less than 30,000 and less than 100,000, but was retained in fractions of Mr greater than 10,000, greater than 30,000 and greater than 100,000. Mitogenic activity was not observed in any fractions subjected to heat treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Superovulation in Sheep: Number and Weight of the Corpora Lutea and Serum Progesterone 1,2

Abstract: To determine similarities and differences between nonsuperovulated and superovulated ewe models, data collected from several experiments (1989 through 2005) were analyzed. Mature non-pregnant non-superovulated (n = 91) or superovulated (n = 299) Western range-type ewes were used for evaluation of luteal function. To induce superovulation, ewes were injected twice daily with FSH on days 13 to 15 of the estrous cycle. At corpora lutea (CL) collection on day 5 or 10 of the estrous cycle, the number of CL was determined. For selected ewes, the CL were weighed and blood samples were collected for determination of progesterone (P4) concentration in serum. Each year, a similar (P > 0.1) number of ovulations/ewe was induced by FSH treatment (range from 12.4 ± 2.0 to 20 ± 2.5/year). Superovulated ewes had greater (P 0.1) for superovulated vs. non-superovulated ewes (2.3 ± 1.1 vs. 1.3 ± 0.1 ng/ml), but on day 10 tended to be greater (P < 0.06) in superovulated than non-superovulated ewes (5.8 ± 1.3 vs. 3.8 ± 0.3 ng/ml). When P4 concentration in serum was expressed per g of luteal tissue mass, values were similar for non-superovulated and superovulated ewes on days 5 and 10 of the estrous cycle. Moreover, all P4 values were greater (P < 0.05) on day 10 than on day 5 of the estrous cycle. Thus, despite some differences in CL number and CL weight, the major function of the CL, P4 production does not seem to be altered in superovulated ewes compared with non-superovulated ewes. Therefore, these data indicate that our superovulated ewe model may be used for studies of luteal function.

Board-invited review: intrauterine growth retardation: implications for the animal sciences.

Abstract: Intrauterine growth retardation (IUGR), defined as impaired growth and development of the mammalian embryo/fetus or its organs during pregnancy, is a major concern in domestic animal production. Fetal growth restriction reduces neonatal survival, has a permanent stunting effect on postnatal growth and the efficiency of feed/forage utilization in offspring, negatively affects whole body composition and meat quality, and impairs long-term health and athletic performance. Knowledge of the underlying mechanisms has important implications for the prevention of IUGR and is crucial for enhancing the efficiency of livestock production and animal health. Fetal growth within the uterus is a complex biological event influenced by genetic, epigenetic, and environmental factors, as well as maternal maturity. These factors impact on the size and functional capacity of the placenta, uteroplacental blood flows, transfer of nutrients and oxygen from mother to fetus, conceptus nutrient availability, the endocrine milieu, and metabolic pathways. Alterations in fetal nutrition and endocrine status may result in developmental adaptations that permanently change the structure, physiology, metabolism, and postnatal growth of the offspring. Impaired placental syntheses of nitric oxide (a major vasodilator and angiogenic factor) and polyamines (key regulators of DNA and protein synthesis) may provide a unified explanation for the etiology of IUGR in response to maternal undernutrition and overnutrition. There is growing evidence that maternal nutritional status can alter the epigenetic state (stable alterations of gene expression through DNA methylation and histone modifications) of the fetal genome. This may provide a molecular mechanism for the role of maternal nutrition on fetal programming and genomic imprinting. Innovative interdisciplinary research in the areas of nutrition, reproductive physiology, and vascular biology will play an important role in designing the next generation of nutrient-balanced gestation diets and developing new tools for livestock management that will enhance the efficiency of animal production and improve animal well being.

Actions of Placental and Fetal Adrenal Steroid Hormones in Primate Pregnancy

Abstract: It is clear that steroid hormones of placental and fetal adrenal origin have critically important roles in regulating key physiological events essential to the maintenance of pregnancy and development of the fetus for extrauterine life Thus, progesterone has suppressive actions on lymphocyte proliferation and activity and on the immune system to prevent rejection of the developing fetus and placenta (see Fig 9) Progesterone also suppresses the calcium-calmodulin-MLCK system and thus activity of uterine smooth muscle, thereby promoting myometrial quiescence to ensure the maintenance of pregnancy Estrogen enhances uteroplacental blood flow and possibly placental neovascularization to provide optimal gas exchange and the nutrients required for the rapidly developing fetus and placenta In turn, estrogen has specific stimulatory effects on the receptor-mediated uptake of LDL by, and P-450scc activity within, syncytiotrophoblasts, thus promoting the biosynthesis of progesterone Moreover, there is an estrogen-dependent developmental regulation of expression of the LDL receptor and NAD-dependent 11 beta-HSD in the placenta, processes reflecting functional/biochemical differentiation of the trophoblast cells with advancing gestation The increase in 11 beta-HSD causes a change in transplacental corticosteroid metabolism, which results in activation of the HPAA in the fetus As a result of this cascade of events, there is an increase in expression of pituitary POMC/ACTH and key enzymes, eg 3 beta-HSD and P-450 17 alpha-hydroxylase, important for de novo cortisol formation by, and consequently maturation of, the fetal adrenal gland In turn, cortisol has well defined actions on surfactant biosynthesis and consequently fetal lung maturation, as well as effects on placental CRH/POMC release, which may be important to the initiation of labor At midgestation, estrogen also selectively feeds back on the fetal adrenal to suppress DHA and maintain physiologically normal levels of estrogen Preparation of the breast for lactation and nourishment of the newborn appears to involve a multifactorial system of regulation that includes estrogen It is apparent, therefore, that autocrine/paracrine, as well as endocrine, systems of regulation are operative within the fetoplacental unit during primate pregnancy A major goal of this review has been to illustrate the critically close functional communication existing between the developing placenta and fetus in the biosynthesis and the actions of steroid hormones during primate pregnancy The functional interaction of the human fetal adrenal and placenta with respect to the biosynthesis of estrogen was demonstrated many years ago However, the recent studies presented in this review show that the endocrine interaction between the fetus and placenta is more extensive, involving complex physiological regulatory mechanisms Thus, as illustrated in Fig 9, estrogen, acting via its receptor within the placenta and other reproductive tissues, orchestrates the dynamic interchange between the placenta and fetus responsible for the developmental regulation of the biosynthesis of the various steroid and peptide hormones and their receptors necessary for the maintenance of pregnancy and development of a live newborn It would appear, therefore, that the immediate and long range challenges in this area of reproductive endocrinology are to employ in vitro molecular and in vivo experimental approaches simultaneously to elucidate the nature of these complex interactions and define the cellular and molecular mechanisms underlying these important regulatory events

Angiogenesis in the Placenta

Abstract: The mammalian placenta is the organ through which respiratory gases, nutrients, and wastes are exchanged between the maternal and fetal systems. Thus, transplacental exchange provides for all the metabolic demands of fetal growth and development. The rate of transplacental exchange depends primarily on the rates of uterine (maternal placental) and umbilical (fetal placental) blood flows. In fact, increased uterine vascular resistance and reduced uterine blood flow can be used as predictors of high risk pregnancies and are associated with fetal growth retardation. The rates of placental blood flow, in turn, are dependent on placental vascularization, and placental angiogenesis is therefore critical for the successful development of viable, healthy offspring. Recent studies, including gene knockouts in mice, indicate that the vascular endothelial growth factors represent a major class of placental angiogenic factors. Other angiogenic factors, such as the fibroblast growth factors or perhaps the angiopoietins, also may play important roles in placental vascularization. In addition, recent observations suggest that these angiogenic factors interact with the local vasodilator nitric oxide to coordinate placental angiogenesis and blood flow. In the future, regulators of angiogenesis that are currently being developed may provide novel and powerful methods to ensure positive outcomes for most pregnancies.

Angiogenesis in the female reproductive system.

Abstract: In adult tissues, capillary growth (angiogenesis) occurs normally during tissue repair, such as in healing of wounds and fractures. Rampant capillary growth is associated with various pathological conditions, including tumor growth, retinopathies, hemangiomas, fibroses and rheumatoid arthritis. The female reproductive organs (i.e., ovary, uterus, and placenta) exhibit dynamic, periodic growth and regression accompanied by equally dramatic changes in rates of blood flow. It is not surprising, therefore, that they are some of the few adult tissues in which angiogenesis occurs as a normal process. Thus, the female reproductive system provides a unique model for studying regulation of angiogenesis during growth and differentiation of normal adult tissues. Ovarian, uterine, and placental tissues recently have been shown to contain and produce angiogenic and anti-angiogenic factors. This review discusses the current state of knowledge regarding angiogenic processes and their regulation in female reproductive tissues. In addition, implications of this research for regulation of fertility as well as for control of angiogenesis in other normal and pathological processes are discussed.

Utero-placental vascular development and placental function.

Abstract: The rate of fetal growth and subse- quent birth weight are major determinants of postna- tal survival and growth. Because the placenta is the organ through which respiratory gases, nutrients, and wastes are transported between the maternal and fetal systems, its primary function is to supply the metabolic substrates necessary to support fetal growth. Placental growth and development, therefore, are critical for normal fetal growth and development. During the last half of gestation in mammals, growth of the fetus is exponential, whereas utero-placental growth slows or ceases. Nevertheless, unless placental transport capacity keeps pace with the continually increasing demands of the fetus, fetal growth will be compromised. Studies over the last two decades have shown that placental transport capacity does indeed keep pace with fetal growth. This increase in placental function can be accounted for primarily by continual increases in placental (uterine and umbilical) blood flows, associated with increased placental vascularity. Placental vascular growth and development, in turn, are probably regulated by angiogenic factors produced by the placental tissues themselves. These placental angiogenic factors are produced primarily by the maternal placental tissues, are heparin-binding, and seem to be related to the fibroblast growth factor family. Further elucidation of the factors responsible for placental growth and vascular development is critical for an improved understanding of utero- placental-fetal interactions, which result in delivery of a healthy offspring.