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SYSTEMIC VERSUS LOCAL HORMONAL REQUIREMENTS FOR BLASTOCYST IMPLANTATION: A HYPOTHESIS ZEEV DlCKMANN* The various features of the hormonal control of blastocyst implantation have been adequately reviewed by others [1, 2]. I shall assemble certain aspects of the hormonal control of implantation which will form the background for presenting a new hypothesis. Because the hormonal control of implantation has been studied more extensively in rat and mouse than in other mammalian species, I shall use the rat as a primary model. Two basic components are required to accomplish implantation: a mature, zona-pellucida-free blastocyst and a properly conditioned uterus. The conditioning of the uterus results from stimulations with progesterone followed by estrogen (the "estrogen surge"). If a pregnant rat is ovariectomized before the occurrence of the estrogen surge and is treated with progesterone, implantation does not take place; the blastocysts enter a phase oflow metabolic activity, but they remain viable in the uterine lumen. Under such conditions, known as "delayed implantation ," when a female is given a single injection of estrogen, implantation begins about 24 hours later. During regular pregnancy as well as during delayed implantation, progesterone is the key hormone for preparing the uterus for implantation. However, a relatively mild estrogen intervention is necessary for the induction of implantation. Thus, during delayed implantation, a subcutaneous injection of 50 ng of estradiol- 1 7/3 suffices to induce implantation [2]. I surmise that the estrogen intervention may cause a slight weakening of the progesterone dominance, but by and large the progesterone dominance is retained. The estrogen ?Department of Gynecology and Obstetrics and Ralph L. Smith Human Development Research Center, University of Kansas Medical Center, Kansas City, Kansas 66103. This study was supported in part by grants from the NIH (1R01-HD08644) and from the National Foundation (1-406). I thank Eleanor Colasanto for typing the manuscript. I dedicate this article to Dr. Oliver P. Pearson, who introduced me in a very positive way to the science of reproductive biology.© 1979 by The University of Chicago. 0031-5982/79/2203-0063$01.00 390 Zeev Dickmann ¦ Hormonal Requirementsfor Implantation intervention is obligatory in rat and mouse, but not in rabbit [3,4], hamster [5, 6], and sheep [7]. Thus, implantation does occur in pregnant ovariectomized-adrenalectomized rabbits and hamsters and in ovariectomized sheep (in which ovariectomy-adrenalectomy studies have not been done) treated with progesterone alone. Due to a lack of large-scale comparative studies, it is not known whether an estrogen-intervention requirement is common or uncommon among mammalian species in general. However, the hypothesis proposed here is applicable regardless of whether or not a species requires an estrogen intervention. Hypothesis A distinction should be made between the preparation ofthe uterus as a whole and the preparation of the actual site of implantation. At the prospective implantation site, an inflammatory-like reaction (e.g., increase in capillary permeability) has to precede implantation [8]. Since it has been demonstrated that progesterone is an antiinflammatory agent [9-12], I postulate that while progesterone dominance is obligatory for the uterus as a whole, it is inhibitory for the local inflammatory-like reaction. Hence, it is compulsory to nullify, or sufficiently reduce, the local progesterone dominance to permit a local inflammatory-like response . A substance to counteract progesterone locally could not be delivered to the uterus via the general circulation as it would affect the entire uterus. Such a substance would have to come from a local source, and the obvious local source is the blastocyst. What is this substance that emanates from the blastocyst? I propose that it is estrogen, for the following reasons: (a) It is well established that estrogen can nullify or reduce the effects of progesterone; (b) it has been shown that rabbit blastocysts contain [13-15] and can synthesize [16] estrogen; (c) there is evidence that in the rat, a few hours before implantation commences, the estrogen concentration is considerably higher in the uterine segments comprising the implantation sites than in the segments comprising the interimplantation areas [17]; (d) it has been demonstrated that a local application of a minute quantity of estrogen, to a properly primed rat uterus, results in a local increase in capillary permeability [18]. Discussion...

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Additional Information

ISSN
1529-8795
Print ISSN
0031-5982
Pages
pp. 390-393
Launched on MUSE
2015-01-07
Open Access
No
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