Medically Assisted Conception An Agenda for Research (1989) / Chapter Skim
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Towards a Cellular and Molecular Understanding of Implantation in the Human: Implications for Assisted Reproductive Technologies
Towards a Cellular and Molecular Understanding of Implantation in the Human: Implications for Assisted Reproductive Technologies
Pages 336-361
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From page 336... ...
INTRODUCTION Successful in vitro fertilization programs report fertilization rates, of 60-75% yet clinical pregnancy rates approximate 20-30% per transfer (Ben Rafael et al., 1986, 1987; Laufer et al, 1984; Lopata 1983~. The large gap between fertilization and pregnancy rates has generally been attributed to failure in the pert-implantation period, a time of wastage following natural conception.
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From page 337... ...
intrusive implantation where trophoblasts insinuate between epithelial cells prior to initiating frank invasion. The latter is the apparent mechanism by which human implantation is initiated based upon the few specimens of early human implantation sites available for study (Enders et al., 1983; Hata et al., 1981 a, b; Pierce et al., 1964~.
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From page 338... ...
Several fundamental questions regarding the fusion competency of trophoblastic cells remain unanswered. What prevents cytotrophoblasts, which lie directly under syncytial trophoblasts in the chorionic villi, from fusing?
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From page 339... ...
The fact that a variety of extracellular matrix proteins support the morphologic differentiation of human cytotrophoblasts in vitro, as well as the outgrowth of mouse blastocysts (Armant et al., 1986) , indicates that the trophoblast expresses a variety - 339
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. We are developing systems to explore the interactions of human trophoblasts with human endometrial explants and purified endometrial glandular epithelial cells in culture (Coutifaris et al., 198S, 1989; Kishimoto et al., 1987; X1iman et al., 1988, 1989~.
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From page 341... ...
Our in vitro models for human implantation assume that isolated cytotrophoblasts, obtained either from first trimester or term placentae, behave like trophectoderm of the blastocyst and that endometrial explants or isolated endometrial cells can retain the characteristics of pert-implantation endometrial tissue in vivo. While it is far too early to know whether these assumptions are legitimate, preliminary data discussed below encourage us to press on with these studies.
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From page 342... ...
incubated hatched human blastocysts onto established monolayer cultures of human endometrial epithelial cells and observed trophoblastic cell attachement and outgrowth. Ultimately, the endometrial cells were displaced and allowed the trophoblasts to come in contact with the culture dish.
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From page 343... ...
reported that the to mouse produces blastocysts which are less invasive than controls and have an associated diminished production of plasminogen activator activity. Other proteases which degrade extracellular matrix such as stromelysin and collagenases probably participate in trophoblast invasion, since a variety of proteins must be hydrolyzed in concert or sequence during implantation.
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From page 344... ...
Physical contact of the blastocyst with the endometrium and carbon dioxide produced by the conceptus have been proposed as "signals" to the endometrium in rodents, but more compelling evidence indicates that histamine, prostanoids and locally generated steroids play the critical roles in the initial events in nidation (Weitiauf, 1988~. It remains to be determined whether these substances have similar functions in human pregnancy.
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From page 345... ...
The primary assumptions regarding the equivalency of cytotrophoblasts to the blastocyst trophectoderm and the maintenance of normal endometrial function under in vitro conditions are still open to question. Perhaps hybrid systems in which endometrial explants and cytotrophoblast interactions occur in an animal host (i.e., nude mouse or rat)
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From page 346... ...
Such knowledge may also shed light on other pathologic conditions including placenta accreta and gestational trophoblastic disease. Immunocytochemistry and in situ hybridization for detection of protease and protease inhibitor protein and mRNAs in normal and abnormal implantation sites will provide useful descriptive information which could yield clues as to the functions of these proteins.
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These data coupled with emerging concepts from in vitro experimentation will advance our knowledge of this critical and still mysterious event in human reproduction.
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N-terminal amino acid sequence of human pregnancy-associated endometrial a~-globulin, an endometrial insulin-like growth factor (IGF) binding protein-evidence for two small molecular weight IGE binding proteins.
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From page 349... ...
Das (1988~. Biosynthesis and turnover of a 34-kDA protein growth factor in human cytotrophoblasts.
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From page 350... ...
and Plasminogen activator inhibitors (PAIs) in human trophoblasts: markers of trophoblast invasion.36th Annual Meeting of the Society for Gynecologic Investigation, San Diego, CA.
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From page 351... ...
Degradation of extracellular matrix by the trophoblastic cells of first-trimester human placentas.
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From page 352... ...
The human villous cytotrophoblast: interactions with extracellular matrix proteins, endocrine function and cytoplasmic differentiation in the absence of syncytium formation.
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From page 353... ...
Plasminogen activator production by trophoblast cells in vitro. Effect of steroid hormones an protein synthesis inhibitors.
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F ~ Strauss ~ 1987 ~ Regulation of urokinase type plasminogen activator production by culture human cytotrophoblasts.
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From page 355... ...
. The donor oocyte program in Norfolk Fifth World Congress on in vitro fertilization and embryo transfer.
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From page 356... ...
. 8-Bromo-3 ' 5 ' aclenosine monophosphate regulates expression of chorionic gonadotropin and fibronectin in human cytotrophoblasts.
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From page 357... ...
. Polylactosamine glycosylation on human fetal placental fibronectin weakens the binding affinity of fibronectin to gelatin e J
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From page 358... ...
^ #, lance ~ ~~ ~ \ 'a ~ T~psin-DNaseO~esllon _^ Aid- ~~ ~ _ ~ ~ _ ~ ~ CuIlure l _ : Pelle11hrough Call Serum l Godly Cen141ugation Figure 1 Isolation of human cYtotropboblasts - 35S
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From page 359... ...
Note that some of the cytotrophoblasts have formed syncytial structures (arrows) during the 24 hour culture period.
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From page 360... ...
Purified human endometrial glands were cocultured with human cytotrophoblasts for 24 h, fixed with Bouin's solution and immunocytochemically stained with antibodies against alpha- hCG using DAB as chromagen. Several darkly stained - - ~ ~ ~ ~ (E)
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From page 361... ...
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