Fertility status in male cirrhotics.
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Biomedical subjects
Publications and source records attributed to J Sengupta.
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We report the first successful culture of 8-cell/morula stage rat embryos in a fully synthetic medium supplemented with 3% crystalline bovine serum albumin. Eighty-four per cent of morulae developed to blastocysts, showing that this is a highly efficient culture medium for in vitro studies on rat pre-implantation embryos. Blastocyst formation was severely inhibited by antioestrogen (nafoxidine 3 microgram/ml) but no further reversal was obtained by giving oestrogen to culture medium containing this antagonist.
Mouse blastocysts collected on Day 4 were cultured for 4 h in Whitten's medium containing 5 micrograms CI-628 citrate, a specific oestrogen antagonist, and transferred to the uteri of pseudopregnant hosts. There was a significant reduction in the number of implantations observed on Day 11 when compared with those from blastocysts which were similarly transferred after culture in medium alone or in medium containing 1 microgram oestradiol-17 beta and 5 micrograms CI-628 citrate. We suggest that this is further evidence for the involvement of embryonic oestrogen in implantation.
CI-628 citrate, an oestrogen antagonist, instilled into the uterine lumen of ovariectomized, progesterone-treated hamsters on Day 3 of pregnancy completely prevented implantations. Normal implantations occurred in the contralateral uterine horn which was pierced by a needle and in horns into which saline was instilled. There was less activity of lysosomal leucylnaphthylamidase in implantation sites than in inter-implantation sites and in the tissues of the CI-628 citrate-treated horns.
Implantation of embryos was studied in mice which had bee ovariectomized on the afternoon of day 4 of pregnancy and injected intraperitoneally with a non-steroidal antioestrogen or control injection. Normal implantations were obtained in the latter mice as indicated from the positive blue-dye sites when animals were killed late in the evening of day 4. Exposure to CI-628, however, led to a significant inhibition in the number of implantations and only a small percentage of the mice exposed to the steroid antagonist showed normal implantation sites. Study of a few lysosomal enzymes in uterine tissues at the time of early embryo attachment revealed a striking change in the activity of leucyl naphthylamidase. The enzyme showed a reduction in its activity only in uterine which contained attached blastocysts. Acid phosphatase, beta-glucuronidase and non-specific esterase did not show any such implantation-specific changes in their activity patterns. A possible role of leucyl naphthylamidase in the attachment of the embryo to the wall of the uterus has been explored.
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Progesterone secretion during the luteal phase influences oviductal and endometrial functions which are essential for embryo viability and implantation in a number of species including primates. Luteal phase estrogen is not essential for progesterone-dependent endometrial receptivity towards implantation and pregnancy in the rhesus monkey and in the human. However, synchronous development of embryo and endometrium is an essential prerequisite for evolutive implantation. Progesterone helps to maintain synchronous development of preimplantation embryo through its action on maternal uterus. The anti-nidatory action of mifepristone, a potent progesterone receptor modulator (PRM) with pronounced antiprogestagenic activity, is known to be associated with desynchronization of endometrium along with repression of glandular secretory differentiation and vascular maturation. Thus, it is likely that early luteal phase administration of mifepristone affects paracrine action of the secretory stage endometrium on the preimplantation stage embryo, and thereby inhibits embryonic development and viability. We shall examine this hypothesis using the rhesus monkey as a primate model.
It is becoming increasingly evident that growth factors and cytokines play crucial roles in the process of blastocyst implantation. Endometrial differentiation and secretions, embryo development and secretions, and embryo-endometrium interaction leading to implantation require continuous and synchronous dialogue between these two compartments involving endocrine and paracrine regulators. In this review, a model of the endocrinology and paracrinology of blastocyst implantation in the primate is described.
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