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- Lalitkumar, PGL, et al.
(författare)
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Endometrial tumor necrosis factor alpha (TNFalpha) is a likely mediator of early luteal phase mifepristone-mediated negative effector action on the preimplantation embryo
- 2005
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Ingår i: Reproduction (Cambridge, England). - : Bioscientifica. - 1470-1626 .- 1741-7899. ; 129:3, s. 323-335
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Tidskriftsartikel (refereegranskat)abstract
- Cytokines and growth factors are important mediators of progesterone-regulated endometrial receptivity and embryo development. Early luteal phase administration of a potent antiprogestin-like mifepristone to the rhesus monkey results in endometrial desynchrony, loss of embryo viability and implantation failure. In the present study, administration of mifepristone (2 mg/kg body weight, s.c.) on day 2 after ovulation resulted in a significant increase (P< 0.01) in the level of tumor necrosis factor α (TNFα) in glandular and vascular compartments of endometrium, and in endometrial secretion and luminal fluid on day 6 after ovulation in the rhesus monkey. There was an associated lag in embryonic development, characterized by delayed mitochondrial maturity, poorly developed junctional complexes, a relative absence of intra-cytoplasmic filaments and a high degree of intra-cellular degenerative features. Exposure of TNFα (0, 0.5, 5, 50 ng/ml) to preimplantation stage mouse embryosin vitroshowed a dose-dependent arrest in growth and development at both morula and blastocyst stages along with ultra-structural features of degeneration similar to those observed in embryos collected from early luteal phase mifepristone-treated monkeys. Thede novosynthesized and released proteins in terms of trichloroacetic acid precipitable35S by morulae and blastocystsin vitroshowed a marked depression following exposure to TNFα compared with control embryos. Based on the above observation and the fact that preimplantation stage embryos express receptors for TNFα, we suggest that increased levels of TNFα in endometrial and luminal compartments around the time of uterine receptivity following early luteal phase administration of mifepristone adversely affect the growth and viability of preimplantation stage embryos.
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- Sengupta, J, et al.
(författare)
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Immunoneutralization of vascular endothelial growth factor inhibits pregnancy establishment in the rhesus monkey (Macaca mulatta)
- 2007
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Ingår i: Reproduction (Cambridge, England). - : Bioscientifica. - 1470-1626 .- 1741-7899. ; 133:6, s. 1199-1211
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Tidskriftsartikel (refereegranskat)abstract
- Maternal endometrial vascular endothelial growth factor (VEGF) is considered important in blastocyst implantation. However, there is no direct evidence to support this conjecture in the primate. In the present study, we have examined this hypothesis by testing whether immunoneutralization of VEGF during the peri-implantation stage of gestation affects embryo implantation in the rhesus monkey. Adult female animals (n = 36) during mated ovulatory cycles were randomly assigned to one of the experimental groups treated subcutaneously with either isotype-matched mouse immunoglobulin (group 1: control, n = 8) or monoclonal mouse antibody against VEGF-A (anti-VEGF Mab; group 2: 10 mg on day 5 after ovulation, n = 8; group 3: 20 mg on day 5 after ovulation, n = 8; group 4: 10 mg on day 10 after ovulation, n = 4; group 5: 10 mg on days 5 and 10 after ovulation, n = 8). Anti-VEGF Mab-treated animals in groups 2–4 did not show any marked inhibition in pregnancy establishment. On pooled analysis, however, anti-VEGF Mab administration in groups 2–5 (n = 28) resulted in a significant (P < 0.04) decline in the number of viable term pregnancy when compared with control animals. The observed difference was explained by the fact that 10 mg anti-VEGF Mab given to each animal on days 5 and 10 after ovulation in group 5 (n = 8) inhibited pregnancy establishment significantly (P < 0.02) when compared with control group 1. There was no significant change in serum concentrations of estradiol-17β, progesterone, and free VEGF among groups. Furthermore, animals treated with anti-VEGF Mab (n = 8) as in group 5 revealed marked decrease in immunoreactive VEGF, fms-like tyrosine kinase-1, and kinase-insert domain region in trophoblast cells associated with shallow uterine invasion on day 13 of gestation when compared with samples from control group animals (n = 8). Thus, VEGF action is required for successful blastocyst implantation in the rhesus monkey.
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- Sengupta, J, et al.
(författare)
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Nitric oxide in blastocyst implantation in the rhesus monkey
- 2005
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Ingår i: Reproduction (Cambridge, England). - : Bioscientifica. - 1470-1626 .- 1741-7899. ; 130:3, s. 321-332
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Tidskriftsartikel (refereegranskat)abstract
- Successful blastocyst implantation depends on the interaction between cells of maternal endometrium and conceptus, as well as adequate blood supply to the site of blastocyst implantation. Nitric oxide (NO) generally plays a significant role in the local regulation of vascular physiology in a variety of mammalian tissue systems, however, its role in blastocyst implantation and placentation in the primate is not known. The aim of the present study was to examine: (i) NADH-diaphorase activity and expression of three isoforms of nitric oxide synthase (NOS), namely endothelial NOS (eNOS), inducible NOS (iNOS) and neuronal NOS (nNOS) in pre-implantation stage monkey embryos, morula (n= 4) and blastocyst (n= 10), as well as, in different compartments of conceptus and maternal endometrium at primary implantation sites during lacunar (n= 6) and villous (n= 9) stages of placentation in the rhesus monkey, and (ii) the potential anti-nidatory effect of vaginal administration of NOS inhibitor during the peri-implantation period of conception cycles in rhesus monkeys. Pre-implantation stage blastocysts exhibited marked NADPH-diaphorase activity along with immunopositive iNOS mainly in the inner cell mass. During the lacunar stage, marked eNOS expression was observed in cytotrophoblast cells lining the embryonic cavity. However, cytotrophoblast cells lining villi, forming columns, and constituting anchoring villi expressed all the three isoforms of NOS in villous placenta stage tissue. During the lacunar stage, eNOS and iNOS protein expressions were observed in epithelial and decidual cells of endometrium. As gestation advanced, mRNAs for all three isoforms of NOS were observed to increase in epithelial and decidual cells, however, with no marked change in protein expression. Vaginal administration of a NOS inhibitor (NG-nitro-l-arginine methyl ester, L-NAME, 4, 6, and 8 mg/kg body weight or aminoguanidine, AG, 4 mg/kg body weight) during days 6 to 12 after ovulation resulted in pregnancy failure in a higher number of animals (L-NAME: 8 confirmed pregnancies in 25 animals; AG: 2 confirmed pregnancies in 8 animals) compared with control animals (5 pregnancies in 7 animals). It appears that NO may play an important role in the establishment of pregnancy in the rhesus monkey.
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