Perfused Human Full-Term Placenta: A New Model for In Vivo Investigation of Aromatase Inhibitors

1987 ◽  
pp. 229-236
Author(s):  
B. Wagner ◽  
A. Niemand ◽  
H. Klein ◽  
H.-P. Leichtweiss ◽  
K.-D. Voigt
1986 ◽  
Vol 25 ◽  
pp. 13
Author(s):  
B. Wagner ◽  
A. Niemond ◽  
H. Klein ◽  
H.-P. Leichtweiss ◽  
K.-D. Voigt

2004 ◽  
Vol 11 (2) ◽  
pp. 179-189 ◽  
Author(s):  
P E L√∏nning

The development of aromatase inhibitors for breast cancer therapy is a result of successful translational research exploring the biochemical effects of different compounds in vivo. Studies assessing plasma oestrogen levels as well as in vivo aromatase inhibition have revealed a consistent difference with respect to biochemical efficacy between the third generation compounds (anastrozole, letrozole and exemestane) and the previous, first and second generation drugs, corresponding to the improved clinical effects of these compounds as outlined in large phase III studies. Thus, endocrine evaluation has been found to be a valid surrogate parameter for clinical efficacy. Moreover, the results from these studies have added important biological information to our understanding of endocrine regulation of breast cancer. Based on the clinical results so far, aromatase inhibitors are believed to play a key role in future adjuvant therapy of postmenopausal breast cancer patients and potentially also for breast cancer prevention. Interesting findings such as the lack of cross-resistance between steroidal and non-steroidal compounds should be further explored, as this may add additional information to our understanding of breast cancer biology.


1962 ◽  
Vol 6 (1) ◽  
pp. 88-106 ◽  
Author(s):  
Johannes A.G. Rhodin ◽  
John Terzakis
Keyword(s):  

1995 ◽  
Vol 144 (3) ◽  
pp. 517-525 ◽  
Author(s):  
S Moslemi ◽  
P Silberzahn ◽  
J-L Gaillard

Abstract Explants of equine full-term placenta have been shown to synthesize 19-norandrogens from labelled androgens. Steroid metabolites were purified by silica-gel column chromatography then analysed and quantified by C18-reverse-phase HPLC coupled to a radioactive flow detector. 19-Norandrostenedione was subsequently recrystallized to constant specific activity, providing unequivocal evidence of its synthesis by the equine placenta. 19-Norandrostenedione synthesis appeared to be localized in the microsomal fraction. Regardless of the substrate used, formation of 19-norandrogens was far weaker than that of oestrogens; moreover, the yield of 17-oxosteroids produced was much greater than that of 17β-hydroxysteroids, suggesting the presence of a dehydrogenase with predominant oxidative activity. Sulphoconjugated steroids formed were less than 0·5% of total steroids. Although 19-nortestosterone could not be generated by equine purified aromatase incubated with labelled testosterone, the synthesis of 19-norandrogens and oestrogens by equine placental explants was blocked by two specific aromatase inhibitors, 4-hydroxyandrostenedione and fadrozole. Our results provide evidence for a placental origin of at least a part of the 19-norandrogens previously identified in the blood of the pregnant mare. Furthermore, it is suggested that 19-norandrogen biosynthesis would involve the enzymatic metabolism of 19-oxygenated androgens formed by equine aromatase. Journal of Endocrinology (1995) 144, 517–525


Placenta ◽  
2021 ◽  
Vol 114 ◽  
pp. 144
Author(s):  
Takanobu Sakurai ◽  
Shiori Suga ◽  
Haruhiko Shimada ◽  
Hironori Takahashi ◽  
Akihide Ohkuchi ◽  
...  

1905 ◽  
Vol s2-49 (193) ◽  
pp. 1-38
Author(s):  
RICHARD ASSHETON ◽  
THOMAS G. STEVENS

1. The full-term after-birth of the elephant consists of a chorion from which spring many much-branched villi, which spread out in all directions into plate-like branches. These end in (a) proximal foliaceous terminations, in which the fœtal blood vessels ramify, which interlace with a complicated system of much larger blood channels filled with maternal blood, having well-defined but non-nucleated walls; (b) more distal lobate terminations, which are covered by a wellmarked columnar or cubical epithelium -- presumably the trophoblast -- which are partly embedded in a kind of coagulum or detritus, and partly appear to hang loosely in irregular blood spaces without walls ; (c) the stems of still more prolonged villi, which have been torn off and probably left embedded in the walls of the uterus; (d) a few torn ends of blood-vessels. 2. The main trunks of the villi and their foliaceous terminations are everywhere separated from the maternal bloodchannels by a syncytial layer, which is continuous with the epithelium covering the lobate terminations, and is presumably trophoblastic. 3. The half-term placenta originally examined by Owen in 1850 shows, in its more central region, characters which are essentially similar to those of the full-term specimen, and goes far to prove the existence of longer villi which penetrate deeply into the uterine mucosa. The lateral areas of the zonary belt exhibit many most interesting previous conditions. We are able to see in these the simple terminations of the foetal villi covered with a single layer of trophoblast separated from the uterine tissues by a layer of matei'ial partly maternal and partly of foetal origin. There is no process of growth round existing maternal capillaries to form an angio-plasmode, nor apparently any phagocytic action on the part of the trophoblast. The vascularisation of the after-birth is effected by the invasion of the trophoblast by extravasated maternal blood, which flows at first in intercellular and intervillous passages which form the larger channels of the after-birth maternal vascular system, and then makes its way along intra-cellular or intrasyncytial canals through a plasmodium produced by the breaking down of the trophoblast of two adjoining villi. We think the evidence is in favour of considering the corpuscles floating in this invading stream, which contains no red non-nucleated corpuscles in its more advanced portions, to be of maternal rather than trophoblastic origin. 4. The tissues of the full-term placenta contain pigment granules, which are deposited chiefly in the syncytial layer. This we regard as an excretory product; it is almost quite absent from the tissues of the half-term specimen. Leucocytes, either of maternal or foetal origin, seem to be concerned in the transference of this pigment into the maternal blood stream. 5. The subcircular bodies of Owen we find as described by him and Turner, though we note the presence of minute villi on their outer surface. 6. We confirm the opinion of previous writers that the zonary band in part is a "deciduous" form of placenta, although there is not much maternal tissue except the blood. It is not correct to speak of the after-birth being composed of a "much hypertrophied mncosa layer of the uterus." 7. The placenta of the elephant shows by its long villi, which tend to remain embedded in the uterus wall, a resemblance to the condition found in the Sirenia; by the villous patches at the poles and other villi which come out from the uterus, either with or without their trophoblastic covering, but with no maternal cells attached, a resemblance to the ungulata vera of the Perissodactyl type ; by the invasion of the trophoblast--if such it is--by the maternal blood stream, a resemblance to the Discoplacental type, although the actual manner by which this invasion occnrs would seem to be--so far as our very limited material affords us opportunity of observation--unlike anything hitherto described.1 8. The resemblance, at first sight obvious enough to the zonary placenta of the carnivora, is superficial. The elephant's placenta differs from that of the carnivora in (a) consisting of three areas of attachment instead of one, two of which, are wholly in the non-deciduous type, the other partly deciduous, partly non-deciduous. (b) There is nothing formed comparable to an angio-plasmode. (c) The maternal capillaries do not directly become the maternal vessels of the after-birth.


2018 ◽  
Vol 243 (5) ◽  
pp. 408-417 ◽  
Author(s):  
Yong-Sub Byun ◽  
Eun-Kyoung Kim ◽  
Kimi Araki ◽  
Ken-ichi Yamamura ◽  
Kihoon Lee ◽  
...  

FRY like transcription coactivator ( Fryl) gene located on chromosome 5 is a paralog of FRY microtubule binding protein ( Fry) in vertebrates. It encodes a protein with unknown functions. Fryl gene is conserved in various species ranging from eukaryotes to human. Although there are several reports on functions of Fry gene, functions of Fryl gene remain unclear. A mouse line containing null mutation in Fryl gene by gene trapping was produced in this study for the first time. The survival and growth of Fryl−/− mice were observed. Fryl gene expression levels in mouse tissues were determined and histopathologic analyses were conducted. Most Fryl−/− mice died soon after birth. Rare Fryl−/− survivors showed growth retardation with significantly lower body weight compared to their littermate controls. Although they could breed, more than half of Fryl−/− survivors died of hydronephrosis before age 1. No abnormal histopathologic lesion was apparent in full-term embryo or adult tissues except the kidney. Abnormal lining cell layer detachments from walls of collecting and convoluted tubules in kidneys were apparent in Fryl−/− neonates and full-term embryos. Fryl gene was expressed in renal tubular tissues including the glomeruli and convoluted and collecting tubules. This indicates that defects in tubular systems are associated with Fryl functions and death of Fryl−/− neonates. Fryl protein is required for normal development and functional maintenance of kidney in mice. This is the first report of in vivo Fryl gene functions. Impact statement FRY like transcription coactivator ( Fryl) gene is conserved in various species ranging from eukaryotes to human. It expresses a protein with unknown function. We generated a Fryl gene mutant mouse line and found that most homozygous mice died soon after their birth. Rare Fryl−/− survivors showed growth retardation with significantly lower body weight compared to their littermate controls. Although they could breed, more than half of Fryl−/− survivors died of hydronephrosis before age 1. Full-term mutant embryos showed abnormal collecting and convoluted tubules in kidneys where Fryl gene was expressed. Collectively, these results indicate that Fryl protein is required for normal development and functional maintenance of kidney in mice. To the best of our knowledge, this is the first report on in vivo Fryl gene functions.


Microsurgery ◽  
1994 ◽  
Vol 15 (12) ◽  
pp. 891-894 ◽  
Author(s):  
Maria Siemionow ◽  
Troy Andreasen ◽  
Leland Chick ◽  
Graham Lister

2005 ◽  
Vol 17 (2) ◽  
pp. 307
Author(s):  
M. Hirabayashi ◽  
M. Kato ◽  
S. Hochi

Since freeze-dried spermatozoa can be stored at ambient or refrigerated temperature, the costs required for maintenance and shipping of spermatozoa can be reduced. To date, viable offspring in mice (Wakayama and Yanagimachi 1998 Nat. Biotech. 16, 639) and rabbits (Liu et al. 2004 Biol. Reprod. 70, 1776) have been produced by intracytoplasmic sperm injection (ICSI) using freeze-dried samples. The objectives of the present study were to examine whether freeze-dried rat spermatozoa can participate in full-term development by ICSI, and whether sonication prior to freeze-drying of the spermatozoa influences the offspring rate. Spermatozoa from cauda epididymides of Sprague-Dawley (SD) rats were collected in 10 mM TRIS/HCl buffer supplemented with 50 mM NaCl and 50 mM EGTA. A 2 × 3 factorial-designed experiment was conducted. The sperm suspensions were either sonicated for 10 s using a 10% power output from an ultrasonic cell disruptor or not sonicated. The sperm suspensions were then processed for freeze-thawing (100-μL sample in 1.0-mL cryotube was cooled in liquid nitrogen vapor, stored at -196°C for 48 h, and thawed in a 25°C water bath) and freeze-drying (100-μL sample in 1.5-mL polypropylene tube was frozen in liquid nitrogen for 20 s, lyophilized for 6 h by a freeze-drying apparatus, stored at 4°C for 48 h, and rehydrated with 100 μL ultra pure water), or were subjected to immediate use for ICSI. The sperm heads were microinjected into denuded SD oocytes using a piezo-driven micropipette 2–4 μm in diameter, as described previously (Hirabayashi et al. 2002 Transgenic Res. 11, 221). The presumptive zygotes were transferred into oviducts of pseudopregnant Wistar female rats. The in vivo developmental potential of rat oocytes microinseminated with fresh, freeze-thawed, and freeze-dried spermatozoa is shown in the table below. Viable rat offspring were produced in all six experimental groups, with the offspring rates at 2.5–35.0%. Sonication treatment of rat spermatozoa to induce membrane disruption and tail/midpiece dissociation from the heads was effective in increasing the offspring rate after ICSI. The positive effect of sperm sonication may be explained as facilitating decondensation of sperm heads by membrane disruption in the spontaneously activating rat oocytes. Thus, successful participation of freeze-dried rat spermatozoa into full-term development was demonstrated by applying the ICSI. Table 1. In vivo development of rat oocytes microinseminated with fresh, freeze-thawed, and freeze-dried spermatozoa


2019 ◽  
Author(s):  
John M. Thomas ◽  
Juan Garcia ◽  
Matthew Terry ◽  
Ileana Lozano ◽  
Susan M. Mahaney ◽  
...  

ABSTRACTMonodelphis domestica, also known as the laboratory opossum, is a marsupial native to South America. At birth, these animals are developmentally equivalent to human embryos at approximately 5 weeks of gestation which, when coupled with other characteristics including the size of the animals, the development of a robust immune system during juvenile development, and the relative ease of experimental manipulation, have made M. domestica a valuable model in many areas of biomedical research. However, their suitability as models for infectious diseases, especially diseases caused by viruses such as Zika virus (ZIKV), is currently unknown. Here, we describe the replicative effects of ZIKV using a fetal intra-cerebral model of inoculation. Using immunohistochemistry and in situ hybridization, we found that opossum embryos and fetuses are susceptible to infection by ZIKV administered intra-cerebrally, that the infection persists long term, and that the infection and viral replication consistently results in neural pathology and may occasionally result in global growth restriction. These results demonstrate the utility of M. domestica as a new animal model for investigating ZIKV infection in vivo. This new model will facilitate further inquiry into viral pathogenesis, particularly for those viruses that are neurotropic, that may require a host with the ability to support sustained viral infection, and/or that may require intra-cerebral inoculations of large numbers of embryos or fetuses.AUTHOR SUMMARYHere we show that the laboratory opossum (Monodelphis domestica) is a valuable new model for studying Zika virus pathogenesis. Newborns are at the developmental stage of 5-week human embryos. Zika virus inoculated on a single occasion into the brains of pups at the human developmental stages of 8-20 weeks post conception replicated in neuronal cells and persisted as a chronic infection until the experimental endpoint at 74-days post infection. In addition, we observed global growth restriction in one of 16 inoculated animals; global growth restriction has been observed in humans and other animal models infected with Zika virus. The results illustrate great potential for this new animal model for high throughput research on the neurological effects of Zika virus infection of embryos and fetuses.


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