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A M Carter

Publications and source records attributed to A M Carter.

At least 19 recordsLinked to original sources

Evolution of the placenta in eutherian mammals.

We review recent advances in our understanding of placental evolution with particular focus on the interhaemal barrier. It seems likely that the non-invasive, epitheliochorial placentation of living eutherians is a derived state. However, there is disagreement on whether the last common ancestor of eutherian mammals had an endotheliochorial placenta or a haemochorial one. Research has been stimulated by improved understanding of the relations between the orders of mammals provided by molecular phylogenetics. In part, the uncertainties arise from doubt about how to root the mammalian tree. Resolution of this issue will require improved taxon sampling in molecular analyses. At the same time, we need to foster research in comparative placentation on relevant taxa, particularly at the ultrastructural level. Only then can we ensure that information available about the placenta is adequate to capitalise on future advances in molecular phylogenetics. Examples are given of recent findings that could benefit cladistic analysis of placental evolution.

Animals↗

Comparative placentation: some interesting modifications for histotrophic nutrition -- a review.

In considering the diversity of Eutherian mammalian placental structure, it is helpful to keep in mind that both phylogenetically and ontogenetically a functional yolk sac placenta precedes development of the chorioallantoic placenta. Usually the chorioallantoic placenta progressively displaces the area of contact of the yolk sac placenta with the endometrium. It is also closely applied to the endometrium, increasing respiratory efficiency but tending to decrease histotrophic nutrition. Catarrhine primates have minimal histotrophic uptake, using haemotrophic mechanisms throughout most of gestation. Rodents, by using partial or complete inversion of the yolk sac, have extensive regions available to histotroph in later pregnancy. Most mammals, however, have developed specialized regions of the chorioallantoic placenta for ingestion of uterine secretions, cell debris and erythrocytes. These regions vary from simple saccular areolae to more complex areolae such as the chorionic vesicles of prosimian primates to specialized haemophagous areas. All such structures are consistently lined by columnar cellular trophoblast. Examples of these structures, many of which can ingest both glandular secretions and erythrocytes (i.e. they are heterophagous), can be found in species whose definitive placenta is epitheliochorial. They are common but not universal in species whose definitive placenta is endotheliochorial and are even found in a few species with definitive haemochorial placentas. Restriction of phagocytosis to regions of columnar cells provides polarized cells appropriately oriented for ingestion, breakdown and transport, and limits the type of ingestion of both beneficial and potentially toxic materials to expendable individual cells.

Allantois↗

Placentation in the rock cavy, Kerodon rupestris (Wied).

Rock cavies are rodents found in the semi-arid caatinga of Brazil. We studied the structure of the rock cavy placenta by light and transmission electron microscopy. The exchange area of the labyrinth was organized in lobes separated by interlobular areas. The interhaemal barrier was syncytial haemomonochorial. The syncytiotrophoblast had recesses in the basal membrane and some invaginations of the apical membrane, but transtrophoblastic channels could not be found. The interlobular regions comprised syncytiotrophoblast, enclosing maternal venous blood channels, and cytotrophoblast. There was a prominent subplacenta composed of cytotrophoblast and syncytiotrophoblast. Microvilli projected into spaces between the cytotrophoblasts and into lacunae within the syncytiotrophoblast. The yolk sac epithelium exhibited coated pits, endocytotic vesicles and larger vacuoles, consistent with a role in protein uptake from the uterine lumen. Tight junctions between these cells provided a barrier to diffusion by the intercellular route. The reproductive biology of the rock cavy differs from other members of the family, including the guinea pig, but the architecture of the placenta remains remarkably constant.

Amnion↗

Adrenomedullin expression during hypoxia in fetal sheep.

AIM: We asked how adrenomedullin (AM), a vasodilator peptide, was distributed in fetal sheep organs and whether expression of AM would be upregulated in response to moderate acute fetal hypoxia in vivo. METHODS: In four sheep at day 126-130 of gestation, nitrogen was added to the inspired air by tracheal infusion to reduce fetal arterial oxygen content for a period of 4 h. Control fetuses were from four ewes given a tracheal infusion of room air. Fetal and maternal blood samples were taken prior to and during hypoxia/sham hypoxia. Fetal tissue samples were frozen for RNA analysis and fixed for immunohistochemistry. RESULTS: In hypoxic fetuses, arterial oxygen content was significantly reduced to 50% compared with sham fetuses with no change in arterial pH in either group. Plasma ACTH levels rose significantly at 2 and 4 h in hypoxic fetuses only. Initial plasma concentrations of AM in control and hypoxic fetuses were 457 +/- 20 and 430 +/- 35 pg mL(-1) and did not change during the experiment. The relative abundance of AM mRNA was placental cotyledons >> lung > cerebral cortex approximately equal to renal cortex > left ventricle approximately equal to right ventricle > adrenal gland > renal medulla > aorta approximately equal to liver. Immunohistochemical staining for AM confirmed distinct labelling in organs with significant expression. AM mRNA level increased significantly in cerebral cortex of hypoxic fetuses. CONCLUSION: Our results show expression of AM in placenta and in several fetal organs in late gestation sheep. AM may participate in the cerebral vasodilatation that is an integral part of the fetal response to hypoxia.

Actins↗

Metformin reduces C-reactive protein but not complement factor C3 in overweight patients with Type 2 diabetes mellitus.

AIMS: To determine the influence of metformin treatment on plasma C-reactive protein (CRP) and complement factor C3. METHODS: A double-blind, placebo-controlled trial of metformin in patients with poorly controlled Type 2 diabetes mellitus and body mass index > 25 kg/m2. CRP and C3 were analysed in stored plasma samples by in-house ELISAs. Patients attended two baseline visits before randomization and subsequently attended at 3, 6, 12 and 24 weeks post randomization. All patients gave informed consent according to a protocol approved by the Leeds Teaching Hospitals Research Ethics Committee. RESULTS: Baseline CRP in the patients randomized to placebo [1.33 (0.79, 2.25) mg/l] and metformin [1.24 (0.89, 1.71) mg/l] were similar (P = 0.8). Baseline CRP correlated with baseline C3 (r = 0.366) and HbA1c (r = 0.327). The difference in ratios of CRP levels at each visit to baseline between placebo- (n = 16) and metformin-treated (n = 26) subjects was significantly different at the 12-week (P = 0.002) and 24-week (P = 0.03) visits. The difference in CRP ratios between the two treatment groups remained significant after accounting for glycaemic control at both visits (P = 0.001 and P = 0.003, respectively). Baseline C3 was correlated with CRP. Baseline C3 was lower in the placebo-treated group [0.97 (0.88, 1.05) mg/ml] compared with the metformin-treated group [1.09 (1.02, 1.17) mg/ml, P = 0.03]. There was no difference in the mean change in C3 at any visit from baseline between placebo- and metformin-treated groups. CONCLUSION: Metformin may have a specific interaction with mechanisms involved in CRP synthesis or secretion, not directly related to improved insulin sensitivity and dampening of chronic inflammation.

C-Reactive Protein↗

Structure of the ovaries of the Nimba otter shrew, Micropotamogale lamottei, and the Madagascar hedgehog tenrec, Echinops telfairi.

The otter shrews are members of the subfamily Potamogalinae within the family Tenrecidae. No description of the ovaries of any member of this subfamily has been published previously. The lesser hedgehog tenrec, Echinops telfairi, is a member of the subfamily Tenrecinae of the same family and, although its ovaries have not been described, other members of this subfamily have been shown to have ovaries with non-antral follicles. Examination of these two species illustrated that non-antral follicles were characteristic of the ovaries of both species, as was clefting and lobulation of the ovaries. Juvenile otter shrews range from those with only small follicles in the cortex to those with 300- to 400-microm follicles similar to those seen in non-pregnant and pregnant adults. As in other species, most of the growth of the oocyte occurred when follicles had one to two layers of granulosa cells. When larger follicles became atretic in the Nimba otter shrew, hypertrophy of the theca interna produced nodules of glandular interstitial tissue. In the tenrec, the hypertrophying theca interna cells in most large follicles appeared to undergo degeneration. Both species had some follicular fluid in the intercellular spaces between the more peripheral granulosa cells. It is suggested that this fluid could aid in separation of the cumulus from the remaining granulosa at ovulation. The protruding follicles in lobules and absence of a tunica albuginea might also facilitate ovulation of non-antral follicles. Ovaries with a thin-absent tunica albuginea and follicles with small-absent antra are widespread within both the Eulipotyphla and in the Afrosoricida, suggesting that such features may represent a primitive condition in ovarian development. Lobulated and deeply crypted ovaries are found in both groups but are not as common in the Eulipotyphla making inclusion of this feature as primitive more speculative.

Animals↗

Altered expression of IGFs and IGF-binding proteins during intrauterine growth restriction in guinea pigs.

The IGF system is one of the most important endocrine and paracrine growth factor systems that regulate fetal and placental growth. We hypothesized that intrauterine growth restriction (IUGR) in guinea pigs is mediated by the altered expression of IGFs and/or IGF binding protein (BP) mRNAs in tissues and is related to growth of specific tissues. IUGR was induced by unilateral uterine artery ligation on day 30 of gestation, and fetal plasma, amniotic fluid and tissue samples were collected at 55-57 days (term about 68 days) from paired IUGR and control fetuses (n=6). Western ligand blotting and immunoblotting were used to compare IGFBP levels in plasma and amniotic fluid. Total RNA was extracted from placenta and fetal tissues, and the relative abundance of IGF-II and IGFBP-1-6 mRNA was determined by Northern blotting, using species-specific probes where available. IUGR fetuses had decreased (P<0.01, by Student's t-test) placental weight and body weight with an increase in the brain:liver weight ratio. The principal IGFBPs in fetal plasma migrated at 40-35, 30 and 25 kDa and were identified as IGFBP-3, -2 and -4 respectively. IUGR was associated with elevated plasma IGFBP-2 and IGFBP-4 and reduced IGFBP-3 levels. IGFBPs were detected at low levels in amniotic fluid of control fetuses but at higher levels in IUGR fetuses. In IUGR placentae, there was a small increase in IGFBP-4 mRNA (P<0.05). IGFBP-2 mRNA increased (P<0.001) in liver of IUGR fetuses. IGF-II and IGFBP mRNA expression did not change in fetal muscle. The results are consistent with reduced IGF action, directly or through inhibition by IGFBPs, particularly by circulating and tissue IGFBP-2, as a potential causal factor in decreased growth of the placenta and certain fetal tissues.

Amnion↗

Placentation in an American mole, Scalopus aquaticus.

In 1938 Mossman reported that epitheliochorial placentation occurred in an insectivore, the Eastern mole. This led to a radical change in his thinking about placental evolution, yet 40 years would pass before the appearance of a definitive description. Unpublished papers in the Mossman Collection at the University of Wisconsin Zoological Museum tell a fascinating story about this delay. The Scalopus material was studied by Mossman's graduate student, M.R.N. Prasad, who concluded that the placenta was initially endotheliochorial and that subsequent re-epithelialization of the uterus led to the definitive epitheliochorial condition. Mossman withheld publication of these findings pending electron microscopic studies. The definitive publication described the ultrastructure of the interhaemal region. Although based on a single specimen, this seemed to justify the conclusion that an epitheliochorial condition was maintained throughout gestation. These findings are discussed in relation to subsequent work on the European mole and current thinking about placental evolution.

Animals↗

Placentation in species of phylogenetic importance: the Afrotheria.

Afrotheria, one of four mammalian superorders, comprises elephants, sea cows, hyraxes, aardvark, elephant shrews, tenrecs and golden moles. Their placentas either form an equatorial band or are discoid in shape. The interhemal region, separating fetal and maternal blood, is endotheliochorial in elephants, aardvark and possibly the sea cows, but hemochorial in the remaining orders. There is a secondary epitheliochorial placenta in elephant shrews while a similar structure in tenrecs erodes maternal tissues. Specialized hemophagous regions are a striking characteristic of some of these placentas yet absent in hyraxes, elephant shrews, and golden moles. It is possible that the common ancestor of the Afrotheria had an endotheliochorial placenta. Establishment of a hemochorial condition, as seen in rock hyraxes, elephant shrews, tenrecs, and golden moles, would be a more recent development. The elephant, manatee, and aardvark all have circumferential placentas. Thus the formation of a discoid placenta with a more or less extensive secondary placenta in elephant shrews and tenrecs would also be a derived state.

Animals↗

Vascular organization of the hystricomorph placenta: a comparative study in the agouti, capybara, guinea pig, paca and rock cavy.

The placental vasculature of five hystricomorph rodents was examined by latex injection of the blood vessels, immunohistochemistry and scanning electron microscopy of vessel casts. The pattern of branching of the vessels is described at the level of fine structure. The placenta is divided into lobes separated by interlobular trophoblast. Fetal arteries course through the interlobular areas and give rise to capillaries from which blood drains into veins at the centre of the lobes. Maternal blood reaches the placenta through spiral arteries that pass around the perimeter of the subplacenta. They supply large maternal blood sinuses, lined by trophoblast, which run through the interlobular areas and into the centre of the lobes. Here they supply fine channels that run parallel to the fetal capillaries, so that maternal blood flows from the centre of the lobe to the periphery. This arrangement provides the morphological basis for countercurrent exchange. The maternal channels of the labyrinth drain into spaces formed by the latticework of the interlobular trophoblast and thence through venous lacunae to a basal venous lacunar ring. The subplacenta is supplied by a single fetal artery. The vessels within the subplacenta pursue a tortuous course with dilatations and constrictions as in an endocrine gland.

Animals↗

What can comparative studies of placental structure tell us?--A review.

The diversity of placental structures in Eutherian mammals is such that drawing generalizations from the definitive forms is problematic. There are always areas of reduced interhaemal distance whether the placenta is epitheliochorial, synepitheliochorial, endotheliochorial or haemochorial. However, the thinning may be achieved by different means. The presence of a haemophagous area as an iron transport facilitator is generally associated with endotheliochorial placentae but is also found in sheep and goats (synepitheliochorial) and in tenrecs and hyaenas (haemochorial). Although similar chorioallantoic placentae are found within families, structure begins to diverge at the ordinal level and there is little correlation at the supraordinal level of phylogeny. Differences in formation and function of the yolk sac provide additional variation. There would appear to be considerable adaptive pressure for development or retention of the haemochorial type of chorioallantoic placenta. This type of placenta has several possible drawbacks including more ready passage of fetal cells to the maternal organism and, should the haemochorial condition be achieved early, oxidative stress. At any rate no animal larger than the human and gorilla has this type of placenta. The endotheliochorial condition is found in animals as large as the bears, manatee and elephants. In addition to the ungulates, the epitheliochorial condition is present in the largest animals with the longest gestation periods, the whales. Considering the length of time since the early stages of mammalian evolution, it is probable that few unmodified structural features are present in any currently surviving mammal. Nevertheless, more complete studies of divergent types of mammalian placenta should help our understanding of mammalian interrelationships as well as placental function.

Adult↗

Placenta and fetal membranes of the four-toed elephant shrew, Petrodromus tetradactylus.

The four-toed elephant shrew is the only extant member of the genus Petrodromus. Some features of its placentation are found in other elephant shrews and may be important in consolidating the elephant shrews in the order Macroscelidea. These include implantation in an embryo chamber at the caudal end of the uterine horn; a large yolk sac; a large, lobulated allantoic sac; a distinct layer of proliferative trophoblastic cells between the labyrinthine and spongy zones of the placenta; an accessory epitheliochorial placenta; and the formation of a mesoplacenta by the decidua basalis. Of particular note are the large granulated cells that occupy the walls of decidual, myometrial and mesometrial arteries. They appear to be uterine natural killer cells. The persistence of a relatively large yolk sac and a large lobulated allantoic sac is a feature which Petrodromus and other elephant shrews share with other members of the superordinal clade Afrotheria.

Animals↗

Vascular reactivity of the preplacental vasculature in Guinea pigs.

The functional correlates of structural remodelling of the preplacental arteries are not well known. We examined the responses of these vessels to vasoactive agents in guinea pigs at mid and late gestation, and attempted to relate them to changes in vessel structure. Segments were taken from the arcade artery, a mesometrial artery near its origin, and an artery near the placenta. They were mounted as rings in a myograph and concentration-response curves were obtained for U46619, endothelin-1 and arginine vasopressin. The vessel segments were then examined by histology and immunohistochemistry. Trophoblast was identified as immunopositive for cytokeratin, circular muscle stained positive for muscle actin and smooth muscle actin, and presumed myofibroblasts in the adventitial layer stained positive only for smooth muscle actin. At both gestational ages, arcade and mesometrial arteries had intact vessel walls. Midgestation placental arteries were characterized by partial or complete disruption of the internal elastic lamina and the presence of a large number of myofibroblasts and of periarterial trophoblast. In late pregnancy, the changes were more extensive, with almost complete dedifferentiation of the smooth muscle cells and trophoblast invasion of the adventitial layer. From midgestation to late gestation, the responses of placental arteries to U46619, endothelin-1 and arginine vasopressin, normalized to the response to K(+)depolarization, were significantly reduced. This suggests that the extensive changes in wall structure in late gestation, which accompany trophoblast invasion, modulate the responses of these vessels to vasoconstrictors. However, mesometrial arteries also demonstrated reduced responsiveness to U46619, suggesting the influence of factors other than trophoblast.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

Helicobacter pylori infection in subjects with acute ischaemic stroke.

AIMS: To determine whether infection with Helicobacter pylori is a significant risk factor for stroke. SUBJECTS: A total 467 in-patients with clinical evidence of acute ischaemic stroke and 388 healthy controls with no evidence of cerebrovascular disease. METHODS: This was a case control study. The prevalence of Helicobacter pylori was measured by enzyme-linked immunosorbent assay in stroke patients and controls. A positive titre was defined as >15 U/ml and relationship with circulating plasma fibrinogen and social depravation was expressed using the Townsend Index. RESULTS: There were significantly more Helicobacter pylori positive individuals (274/398 (69%)) in the cases compared to the controls (206/352 (58.5%)). Fibrinogen levels were also significantly higher in Helicobacter pylori positive (mean 4.14, standard deviation 1.33) than negative individuals (mean 3.78, standard deviation 1.28). The association between Helicobacter pylori and stroke was lost in a logistic model controlling for socio-economic status. Furthermore, fibrinogen levels were not associated with Helicobacter pylori status in a linear regression model controlling for socio-economic status. CONCLUSIONS: Infection with Helicobacter pylori is associated with an increased risk of stroke and increased fibrinogen levels but these findings can be attributed to a confounding effect of socio-economic status.

Aged↗

Soluble P-selectin levels, P-selectin polymorphisms and cardiovascular disease.

P-selectin is a member of the selectin family of cell adhesion molecules which are important in the transient attachment of leukocytes to endothelial cells and platelets. A number of polymorphisms in the gene encoding P-selectin have been identified. Objectives were to investigate the relationship of soluble P (sP)-selectin with P-selectin gene polymorphisms and coronary artery disease (CAD). Two hundred and forty-nine patients, with extent of CAD characterized by >or=50% stenosis in one or more coronary arteries, and 252 healthy controls were studied. Soluble P-selectin was significantly higher in the patients than controls after adjustment for age, sex and smoking [patients 49.8 (47.5-52.1) ng mL-1; controls 46.7 (44.5-49.1) ng mL-1, P = 0.03). There was no association of sP-selectin with myocardial infarction (MI) or presence of >or=50% stenosis. The -1817 T/C, -1969 G/A and -2123 C/G (but not the Thr715Pro) polymorphisms were in strong linkage disequilibrium. The Thr715Pro polymorphism was significantly associated with sP-selectin even after adjustment for covariates [TT 48.9 (46.9-50.0) ng mL-1; TP + PP 40.7 (38.1-43.6) ng mL-1, P < 0.0001]. A significant interaction of Thr715Pro and smoking status was identified in the determination of sP-selectin levels. There was no significant association of genotype at any of the polymorphism in relation to MI or stenosis. The Thr715Pro polymorphisms is associated with plasma sP-selectin. This association is modulated by smoking, although the underlying mechanism remains unclear.

Aged↗