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Biomedical subjects

A C Enders

Publications and source records attributed to A C Enders.

At least 19 recordsLinked to original sources
PubMed2005

Suppression of extravillous trophoblast invasion of uterine spiral arteries by estrogen during early baboon pregnancy.

The present study determined whether estrogen plays a role in regulating invasion and remodeling of the uterine spiral arteries by extravillous trophoblasts during early baboon pregnancy. The level of trophoblast invasion of spiral arteries was assessed on day 60 of gestation (term is 184 days) in baboons untreated or treated on days 25-59 with estradiol or aromatizable androstenedione. The administration of estradiol or androstenedione increased (P<0.01) maternal serum estradiol levels approximately 3-fold above normal. The mean+/-SE percentage of spiral arteries/arterioles invaded by extravillous cytotrophoblasts in estradiol-treated baboons for vessels with diameters of 26-50 microm (0.0+/-0.0), 51-100 microm (1.2+/-0.7) and >100 microm (13.2+/-5.5) was 100%, 90%, and 75% lower (P<0.001), respectively, than in untreated baboons (2.4+/-1.2%; 11.0+/-5.5%, and 54.5+/-8.5%, respectively). Similar results were obtained with androstenedione treatment. However, the distribution of uterine spiral arteries grouped by diameter or number of arteries per basal plate area, i.e. microvessel density, were similar in untreated and estrogen-treated baboons. We suggest, therefore, that the low levels of estrogen exhibited during early primate pregnancy are required to permit normal progression of trophoblast vascular invasion and that the surge in estrogen which occurs during the second-third of normal pregnancy has a physiological role in suppressing further arterial trophoblast invasion. Consequently, we propose that the estrogen-dependent restraint of spiral artery invasion/remodeling ensures optimal blood flow dynamics across the uteroplacental vascular bed to promote normal fetal growth and development.

Animals↗
PubMed2005

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↗
PubMed2004

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↗
PubMed2004

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↗
PubMed2003

IL-11 and IL-11Ralpha immunolocalisation at primate implantation sites supports a role for IL-11 in placentation and fetal development.

Embryo implantation, endometrial stromal cell decidualization and formation of a functional placenta are critical processes in the establishment and maintenance of pregnancy. Interleukin (IL)-11 signalling is essential for adequate decidualization in the mouse uterus and IL-11 promotes decidualization in the human. IL-11 action is mediated via binding to the specific IL-11 receptor alpha (IL-11Ralpha). The present study examined immunoreactive IL-11 and IL-11Ralpha in cycling rhesus monkey endometrium, at implantation sites in cynomolgus and rhesus monkeys and in human first trimester decidua and defined distinct spatial and temporal patterns. In cycling rhesus monkey endometrium, IL-11 and IL-11Ralpha increased in both basalis and functionalis regions during the secretory compared with the proliferative phase, with changing cellular locations in luminal and glandular epithelium and stroma. The patterns were similar overall to those previously described in human endometrium. Differences were seen in immunostaining during implantation in cynomologus and rhesus monkey. In the cynomolgus, very little staining for IL-11 or IL-11Ralpha was seen in syncytio- and cyto-trophoblast cells in the villi between days 12 and 150 of pregnancy although there was moderate staining in cytotrophoblast in the shell between days 12 and 17 and in subpopulations of cytotrophoblast cells invading the arteries at day 17. By contrast in the rhesus monkey between days 24 and 35 of pregnancy and in human first trimester placenta, cyto- and syncytio-trophoblast in the villi but not cytotrophoblast in the shell were positively stained. The most intense staining for both IL-11 and IL-11Ralpha was present within the decidua in the maternal component of implantation sites in all three primates but moderate staining was also present in maternal vascular smooth muscle and glands perivascular cells and epithelial plaques. These results are consistent with a role for IL-11 both during decidualization and placentation in primates.

Animals↗
PubMed2002

Implantation in the nine-banded armadillo: how does a single blastocyst form four embryos?

In the course of a study on reproduction in the nine-banded armadillo, conceptuses between the beginning of implantation and primitive streak formation were examined to determine the manner of trophoblast differentiation during invasion of the endometrium and the sequence involved in formation of four identical quadruplets. The armadillo blastocyst implants in the fundic recess of the uterus. A single amnion and cup-shaped epiblastic plate are formed, and an exocelom develops between the amnion and trophoblast of the implantation site. Loss of the abembryonic trophoblast exposes both visceral and parietal endoderm to the uterine lumen, inverting the yolk sac. Continued expansion of the exocelom facilitates the intrusion of the forming conceptus into the uterine lumen and is accompanied by enlargement of the epiblastic plate. Separate areas of condensations of epiblast cells are the first indication of formation of the four identical quadruplets. The single layer of microvillous trophoblast with basal infoldings (designated absorptive trophoblast) is most likely to contribute extensively to movement of fluid into the exocelom. The resulting expansion of the exocelom not only enlarges the implantation site but also displaces the collapsing common amnion, limiting the amnion to the areas of the forming embryos.

Animals↗
PubMed2002

Equine oocyte maturation with epidermal growth factor.

Epidermal growth factor (EGF) has been shown to have a positive effect during oocyte in vitro maturation in several species. This study was performed to establish the capacity of equine oocytes to undergo nuclear maturation in the presence of EGF and to localise its receptor in the equine ovary by immunohistochemical methods. Oocytes were obtained by aspiration and subsequent scraping from equine follicles (15-25 mm diameter) and cultured in 3 different treatment groups for 36 h: control Group (modified TCM 199 with 0.003% BSA), EGF Group (TCM-199 supplemented with 50 ng/ml EGF) and EMS Group (TCM 199 supplemented with 10% v/v oestrous mare serum). Each group was divided further into 3 treatments with tyrphostin A-47, a specific tyrosine kinase inhibitor, at 0, 10(-4) and 10(-6) mmol/l. Maturation was determined as the percentage of oocytes reaching metaphase II stage at the end of the culture period. Immunohistochemical detection of EGF-receptor (EGFR) was performed using a streptoavidin-biotin method. The recovery rate and oocyte retrieval were 84.6% (recovered oocytes/follicles aspirated) and 6.55 (oocytes/mare), respectively. Treatment with EGF significantly (P<0.05) increased the incidence of metaphase II stage compared with the control group (69.4 vs. 26.9% in controls, respectively). The specific-tyrosine kinase inhibitor A-47 was effective in suppressing EGF-effect on EGF-cultured oocytes; no significant differences were observed in EMS-supplemented oocytes when cultured with A-47. EGF-receptor was localised in follicles, with localisation being more prominent in the cumulus than in mural granulosa cells. This finding, together with the increase of oocyte nuclear maturation rate when using EGF in culture media and the inhibition of maturation by tyrphostin A-47, suggests a physiological role for EGF in the regulation of equine oocyte maturation. The results should help successful development of assisted reproductive technology in the horse.

Animals↗
PubMed2001

Structure of anchoring villi and the trophoblastic shell in the human, baboon and macaque placenta.

Anchoring villi of first trimester placentae of the macaque, baboon and human were examined by light and electron microscopy. The anchoring villi of the baboon and macaque are similar in having more elongated cell columns than those of the human and in having more extracellular matrix between cytotrophoblast cells. These species also have a thicker and more uniform trophoblastic shell. The generative region of cytotrophoblast cells adjacent to the villous mesenchyme is similar in all three species, with the aspect of the core abutting this area being lined by a thickened basal lamina. Similarly, migratory cytotrophoblast cells form extracellular matrix in all three species, but matrix-rich regions of the anchoring villi and shell are more extensive in the non-human primates. The extracellular matrix and especially the material resembling fibrillin may serve to strengthen the villi, particularly the elongated villi of the non-human primate, and also may prevent maternal cells migrating into the trophoblastic shell. The baboon and macaque cytotrophoblast cells that form this matrix tend to be linked by gap and desmosomal junctions and are in contiguous arrays, whereas those in the human that are blocked from reaching normal decidua form abundant extracellular matrix but have no gap junctions. Whether the lack of extensive invasion of the endometrium by baboon and macaque cytotrophoblast cells is related to the increased amount of extracellular matrix, their greater distance from the mesenchymal core, or their intercellular linkages is not known. The investigation of isolated villi from the macaque or baboon, as has been extensively carried out in the human, might help to determine whether the cytotrophoblast cells are intrinsically different or are responding to different environmental cues.

Animals↗
PubMed2001

Early implantation events in the baboon (Papio anubis) with special reference to the establishment of anchoring villi.

The development of the baboon anchoring villus has been studied from day 14 to day 48 of gestation, using light and electron microscopy. At day 14, cords of trophoblast could be seen streaming into the endometrium, invading maternal vessels and forming blood-filled lacunae; by 20 days gestation some of these had differentiated into distinctive anchoring villi, with an outer covering of syncytiotrophoblast and inner cytotrophoblast cells which differed from those of floating villi in that a subpopulation detached from the syncytium to form an interconnecting network of cells within the centre of the villus. Subsequent migration of cytotrophoblast into the endometrium formed the cytotrophoblastic shell while fibrillin-like extracellular matrix biosynthesis within the body of the villus provided a firm mechanical support. At the trophoblast-decidual interface, a zone of necrosis and phagocytosis initially developed, which became less extensive with time, so that by 40 days a stable interface was evident with only residual pockets of necrosis. During this period, there was differentiation of decidual cells which by 28 days developed characteristic pedunculated cell processes, and later became surrounded by a basal lamina. The factors that control detachment of cytotrophoblast from the syncytium and the biosynthesis of the specialized, fibrillar extracellular matrix, features that are not apparent in other placental villi, require further investigation, possibly by carefully controlled in vitro experimentation.

Animals↗
PubMed2001

Expression and localization of thioredoxin during early implantation in the marmoset monkey.

Thioredoxin is a powerful redox protein expressed in invasive cytotrophoblasts and essential for blastocyst implantation in mice. Isolated marmoset thioredoxin cDNA showed that the deduced amino acid sequence differed from the human sequence by four amino acids. The close homology of thioredoxin in the two species enabled us to use monoclonal antibodies against human thioredoxin to detect marmoset thioredoxin in implantation sites, blastocysts and culture medium. Immunocytochemistry on marmoset implantation sites, on pregnancy days 12 and 15, showed that thioredoxin is highly expressed in uterine luminal epithelium, glands and in some endometrial stromal cells. In attached blastocysts, thioredoxin staining was detected in mural and polar trophoblast cells and both visceral and parietal endoderm, whereas no staining was present in the inner cell mass. A similar pattern of thioredoxin expression was detected in hatched blastocysts attached to Matrigel in tissue culture. Trophoblastic vesicles derived from blastocysts expressed thioredoxin in inner endoderm-like cells and outer trophoblast-like cells and secreted thioredoxin into the culture medium. These experiments have demonstrated thioredoxin expression during early stages of embryo-maternal interaction. We propose that thioredoxin protects the early placenta from oxidative damage and that the marmoset is a valuable model for studying thioredoxin regulation and function during implantation and blastocyst differentiation.

Amino Acid Sequence↗
PubMed2001

Influence of epidermal growth factor on mammalian oocyte maturation via tyrosine-kinase pathway.

Epidermal growth factor (EGF) has been reported to promote different functions in mammalian ovaries, including oocyte maturation. The aim of the present study was to establish: that EGF influences oocyte maturation in ovine and equine, that a tyrosine kinase-dependent intracellular mechanism mediates EGF effect and, that EGF-R receptor is detectable in ovarian follicles by immunohistochemistry methods. Selected ovine and equine oocytes were aspirated from 2-5 mm (ovine) or 25 mm (equine) follicles and cultured in TCM 199 for 22 (ovine) or 36 hours (equine). They are then subjected to culture with EGF and two specific tyrosine-kinase inhibitors (TKIs, tyrphostins A-23 y A-47). Maturation was determined as the percentage of oocytes at metaphase II stage after culture. Treatments with EGF significantly increased incidences of metaphase II stage compared to controls (86.2% vs. 55% and 70.4% vs. 22.5% in ovine and equine oocytes, respectively). Tyrphostins A-23 and A-47 were effective in suppressing EGF-effect on oocytes. EGF-receptor was localized in follicles, being more prominent in cumulus and granulosa cells. These results confirm that EGF has a physiological role in the regulation of oocyte maturation via tyrosine-kinase pathway.

Animals↗
PubMed2001

Influence of epidermal growth factor on mammalian oocyte maturation via tyrosine-kinase pathway.

Epidermal growth factor (EGF) has been reported to promote different functions in mammalian ovaries, including oocyte maturation. The aim of the present study was to establish: that EGF influences oocyte maturation in ovine and equine, that a tyrosine kinase-dependent intracellular mechanism mediates EGF effect and, that EGF-R receptor is detectable in ovarian follicles by immunohistochemistry methods. Selected ovine and equine oocytes were aspirated from 2-5 mm (ovine) or 25 mm (equine) follicles and cultured in TCM 199 for 22 (ovine) or 36 hours (equine). They are then subjected to culture with EGF and two specific tyrosine-kinase inhibitors (TKIs, tyrphostins A-23 y A-47). Maturation was determined as the percentage of oocytes at metaphase II stage after culture. Treatments with EGF significantly increased incidences of metaphase II stage compared to controls (86.2% vs. 55% and 70.4% vs. 22.5% in ovine and equine oocytes, respectively). Tyrphostins A-23 and A-47 were effective in suppressing EGF-effect on oocytes. EGF-receptor was localized in follicles, being more prominent in cumulus and granulosa cells. These results confirm that EGF has a physiological role in the regulation of oocyte maturation via tyrosine-kinase pathway.

Animals↗
PubMed2000

Trophoblast-uterine interactions in the first days of implantation: models for the study of implantation events in the human.

The most profound changes in the relationship of the trophoblast to endometrial tissues occur in the first 5 days after the initiation of implantation. Not only have the earliest stages--adhesion and epithelial penetration--never been seen in the human, but also the trophoblastic plate and lacunar stages that follow are not available for modern investigative methods. Studies of appropriately timed endometrium and of trophoblast- and endometrium-derived cell lines have important implications for aspects of implantation. Use of nonhuman primates and other animal models for appropriate stages in implantation could further our understanding of direct trophoblast-uterine interactions. The mechanisms involved in epithelial penetration by infiltration of the syncytial trophoblast into the uterine luminal epithelium could be studied profitably using the marmoset or the ferret. Drawing of the blastocyst into an interstitial location might be investigated in the guinea pig. Formation of trophoblastic lacunae can be investigated in the cynomolgus monkey. By using such animal models of events of implantation in situ, implications concerning the molecules involved in adhesion, penetration of junctional complexes, and uterine vessel invasion that have been derived from in vitro or murine studies may be placed in context.

Animals↗
PubMed1999

Implantation in the marmoset monkey: expansion of the early implantation site.

This study was initiated to examine the early stages of trophoblast adhesion and invasion during implantation in the marmoset. Seven implantation sites were found in the uteri of four marmosets taken between days 13 and 15 of gestation. Three implantation sites in two uteri were examined in detail by electron microscopy. Between days 13 and 15, the marmoset implantation site expanded peripherally by adding areas where syncytial trophoblast penetrated between uterine luminal epithelial cells. Such penetrating masses often bridged openings of endometrial glands, shared junctional complexes with the uterine epithelial cells between which they are infiltrating, and subsequently reached the residual basal lamina of the uterine luminal epithelium. Centripetal to the peripheral region was an intermediate region in which syncytial trophoblast overlay individual clusters of epithelial cells and rested along the basal lamina. In this region there was some evidence of fusion of syncytial trophoblast with uterine epithelial cells. In the central region of the implantation site near the inner cell mass and amnion the trophoblast formed elaborate lamellipodia in relation to the basal lamina. In one of the three specimens examined with electron microscopy there were two foci where trophoblast penetrated through the basal lamina. It was also in the central region that trophoblast penetrated farthest into the uterine glands. The gland cells closest to trophoblast were less closely associated and lost their columnar shape, forming large round cells similar to the epithelial plaque cells of other primates. Where two blastocysts implanted on the same side of the uterus a conjoint membrane was formed which in regions consisted solely of syncytial trophoblast with two basal surfaces and two basal laminas. The prolonged period of time when the implantation site expands within the plane of the uterine epithelium (trophoblastic plate stage) and the peripheral to central sequence in extent of development make this primate a particularly useful animal for studies of trophoblast adhesion to and penetration of the uterine luminal epithelium.

Amnion↗
PubMed1999

Equine placental cup cells show glycan expression distinct from that of both chorionic girdle progenitor cells and early allantochorionic trophoblast of the placenta.

Using lectin histochemistry on plastic-embedded material, the glycosylation patterns of equine girdle and cup cells, and associated endometrial glands, have been investigated from 37 to 67 days gestation. Results were compared with the glycosylation of the 50-day allantochorionic trophoblast of the established equine placenta that will later form the microcotyledons. The differentiated cup cells, which secrete equine chorionic gonadotropin (eCG), showed a pattern of glycosylation that was distinct both from the progenitor girdle cells and the allantochorionic trophoblast, with granules that bound lectins indicating high levels of alpha2,6 and alpha2,3-linked sialic acid, N-acetyllactosamine and bi/tri antennary non-bisected and bisected complex N-glycan. This is consistent with the known carbohydrate content of eCG. In contrast, the allantochorionic trophoblast at 50 days lacked detectable amounts of sialic acid and showed high levels of tri/tetra-antennary non-bisected complex N-glycan and N-acetyl galactosamine which was absent in the cup cells. During the process of girdle cell migration into maternal tissues, the uterine glands became greatly enlarged and dilated basally, with increased amounts of glycosylated secretory products revealed by lectins, which often seeped out into the extracellular space via ruptures in the apical regions of the gland wall.

Animals↗
PubMed1998

Possible significance of cells within intraluminal collagen masses in equine oviducts.

In addition to the unique feature of retention of unfertilized ova, the oviducts of mares frequently contain large intraluminal masses with a fibrillar component and some cells. The aim of this study was to identify the cells and examine their relationship to the extracellular components of these masses. Intraluminal masses were examined both in situ and flushed from the oviducts. The nature of the contained cells and their relationship to the fibrils were examined by light microscopy and by transmission and scanning electron microscopy. In some mares the large masses distended the oviduct, but neither loss of the oviductal epithelium nor damage to this epithelium was seen. Electron microscopy verified that the principal cellular component was fibroblasts, and that the fibrils were type I collagen. Collagen masses collected shortly after ovulation frequently contained viable fibroblasts with collagen fibrils associated with their cell surfaces and with surface clefts. Although such collagen masses were present in pregnant and nonpregnant mares, masses with viable fibroblasts were chronologically associated with recent ovulation. It was concluded that connective tissue drawn into the oviduct at ovulation is retained, and collagen synthesis continues at least for a few days. Although the fibroblasts eventually disintegrate, the collagen remains and may in some cases aggregate within the oviductal lumen to the extent that oviductal transport and embryonic viability could be affected.

Animals↗