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Jeffrey T Jensen - One of the best experts on this subject based on the ideXlab platform.
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polidocanol induced tubal occlusion in nonhuman primates immunohistochemical detection of collagen i v
Contraception, 2016Co-Authors: Jeffrey T Jensen, S Yao, Ov D Slayden, Dong Ock LeeAbstract:Objective Intrauterine Administration of polidocanol foam (PF) can create fallopian tube occlusion in nonhuman primates. The objective of this study was to determine if PF-induced tubal obstructions contain collagen in the extracellular matrix.
Hiroshi Fujiwara - One of the best experts on this subject based on the ideXlab platform.
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dual positive regulation of embryo implantation by endocrine and immune systems step by step maternal recognition of the developing embryo
American Journal of Reproductive Immunology, 2016Co-Authors: Hiroshi Fujiwara, Yoshihiko Araki, Kazuhiko Imakawa, Shigeru Saito, Takiko Daikoku, Minoru Shigeta, Hideharu Kanzaki, Takahide MoriAbstract:In humans, HCG secreted from the implanting embryo stimulates progesterone production of the corpus luteum to maintain embryo implantation. Along with this endocrine system, current evidence suggests that the maternal immune system positively contributes to the embryo implantation. In mice, immune cells that have been sensitized with seminal fluid and then the developing embryo induce endometrial differentiation and promote embryo implantation. After hatching, HCG activates regulatory T and B cells through LH/HCG receptors and then stimulates uterine NK cells and monocytes through sugar chain receptors, to promote and maintain pregnancy. In accordance with the above, the Intrauterine Administration of HCG-treated PBMC was demonstrated to improve implantation rates in women with repeated implantation failures. These findings suggest that the maternal immune system undergoes functional changes by recognizing the developing embryos in a stepwise manner even from a pre-fertilization stage and facilitates embryo implantation in cooperation with the endocrine system.
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Intrauterine Administration of autologous peripheral blood mononuclear cells increases clinical pregnancy rates in frozen thawed embryo transfer cycles of patients with repeated implantation failure
Journal of Reproductive Immunology, 2011Co-Authors: Osamu Okitsu, Machiko Kiyokawa, Takashi Oda, Kaoru Miyake, Yukiyasu Sato, Hiroshi FujiwaraAbstract:Intrauterine Administration of autologous peripheral blood mononuclear cells (PBMC) activated by HCG in vitro are reported to improve implantation rates in patients with repeated failure of IVF-ET. In this study, we examined the effects of Intrauterine Administration of freshly isolated PBMC on clinical pregnancy and the implantation rates of patients who received frozen/thawed embryo transfer by prospective cohort study. Patients who had not achieved a successful pregnancy despite at least one or more IVF-ET sessions were enrolled in this study (n = 253, 253 cycles). Based on the patient's treatment preferences, PBMC were freshly isolated from each patient and then administered to the Intrauterine cavity of that patient. Frozen/thawed embryo transfer was performed and the success of implantation in the PBMC-treated group (n = 83, 83 cycles) was compared with that in the non-treated control groups (n = 170, 170 cycles). There were no significant differences in the clinical pregnancy rate (34.9% vs. 32.9%), implantation rate (21.6% vs. 21.1%) and live birth delivery rate (21.7% vs. 21.8%) between PBMC-treated and non-treated groups. However, when the analyses were restricted to patients who had three or more implantation failures, the clinical pregnancy rate and the implantation rate in the PBMC-treated group (42.1% and 25.0%, p<0.05; n = 19 and 32, respectively) were significantly higher than those in the non-treated group (16.7% and 9.4%, p<0.05; n = 36 and 64, respectively). These findings indicate that Intrauterine Administration of autologous PBMC freshly isolated from patients, effectively improves embryo implantation in patients with three or more IVF failures.
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Intrauterine Administration of peripheral blood mononuclear cells enhances early development of the pre implantation bovine embryo
Molecular Reproduction and Development, 2010Co-Authors: Atsushi Ideta, Hiroshi Fujiwara, Kazuhiko Imakawa, Koh Hayama, Yuuki Nakamura, Toshihiro Sakurai, Kanami Tsuchiya, Sachi Tanaka, Takahiro Yamaguchi, Yoshito AoyagiAbstract:Intrauterine Administration of peripheral blood mononuclear cells (PBMCs) prior to bovine embryo transfer (ET) was previously shown to improve the pregnancy rate. To better understand how PBMCs improve the pregnancy rate, we examined gene expression in the cells from uterine lumen and evaluated the morphology of bovine pre-attachment embryos in utero following Intrauterine Administration of PBMCs. On day 3 of the estrous cycle (day 0 = estrous), bovine PBMCs were isolated and suspended in RPMI 1640, and were incubated for 24 hr. The cultured PBMCs were administered non-surgically to the uterine horn ipsilateral to the corpus luteum on day 4 of the estrous cycle (PBMC group). On day 9, endometrial–luminal lymphoid cells from uterine lumen ipsilateral to the corpus luteum were collected by uterine flushing. Transcripts for macrophage-colony stimulating factor in the lymphoid cells were more abundant in the PBMC group than in the control group (P < 0.05). On day 7 (of the separate experiments), five blastocysts were each transferred to the luminal area, to which PBMCs had been administered on day 4. These embryos were allowed to develop in utero until day 15 of gestation, when embryos were non-surgically retrieved from the uterus. The average length of trophoblasts recovered from the PBMC group was significantly longer than that of the control group (51.6 ± 7.8 vs. 27.4 ± 6.0 mm, P < 0.05). Our results strongly suggest that Intrauterine Administration of PBMCs improves endometrial environment, which promotes early development of pre-attachment conceptuses. Mol. Reprod. Dev. 77:954–962, 2010. © 2010 Wiley-Liss, Inc.
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do circulating blood cells contribute to maternal tissue remodeling and embryo maternal cross talk around the implantation period
Molecular Human Reproduction, 2009Co-Authors: Hiroshi FujiwaraAbstract:In early pregnancy, human chorionic gonadotrophin (HCG) stimulates the corpus luteum (CL) of pregnancy to produce progesterone, which in turn maintains human embryo implantation in the uterus. In addition to this embryo-maternal cross-talk via the endocrine systems through blood circulation, accumulating evidence suggests that circulating blood cells also play an important role in embryo implantation. Peripheral blood mononuclear cells (PBMC) derived from pregnant women increased the progesterone production by luteal cells and promoted the invasion of embryos in vitro. Recombinant-HCG increased chemokine production by PBMC through lectin-glycan interaction and enhanced the effects of PBMC on embryo invasion. Later, it was shown that not only PBMC, but also circulating platelets were possible sources of these chemokines that promote extravillous trophoblast invasion to reconstruct maternal endometrial artery. Circulating platelets were also proposed to induce neovascularization during CL formation. Furthermore, Intrauterine Administration of autologous PBMC effectively improved live birth, pregnancy and implantation rates in patients with repeated (four or more) implantation failures during in vitro fertilization therapy. These findings suggest that circulating blood cells positively contribute to maternal tissue remodeling and embryo-maternal cross-talk around the implantation period in cooperation with the endocrine system.
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Intrauterine Administration of autologous peripheral blood mononuclear cells promotes implantation rates in patients with repeated failure of ivf embryo transfer
Human Reproduction, 2006Co-Authors: Shinya Yoshioka, Hiroshi Fujiwara, Takahiro Nakayama, Kenzo Kosaka, T Mori, Shingo FujiiAbstract:Background There are few effective approaches to infertile patients with repeated failure in IVF-embryo transfer therapy. Since recent evidence suggests that some populations of maternal immune cells positively support embryo implantation, we have developed a new approach using peripheral blood mononuclear cells (PBMCs). Methods Patients who had not experienced successful pregnancy despite four or more IVF-embryo transfer sessions were enrolled in this study (n = 35, 35 cycles). PBMCs were obtained from patients on the day of oocyte retrieval and were cultured with HCG for 48 h. Two days later, PBMCs were freshly isolated from patients again, combined with cultured PBMC and then administered to the Intrauterine cavity of the patients. Blastocyst transfer was performed on day 5, and the success of implantation in the PBMC-treated group was compared with that in the non-treated group. Results Clinical pregnancy rate, implantation rate and live birth rate in the PBMC-treated group (41.2, 23.4 and 35.3%; n = 17, 47 and 16, respectively) were significantly higher than those in the non-treated group (11.1, 4.1 and 5.5%; n = 18, 49 and 18, respectively). Conclusion Intrauterine Administration of autologous PBMC may be an effective approach to improve embryo implantation in patients with repeated IVF failures.
Ov D Slayden - One of the best experts on this subject based on the ideXlab platform.
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polidocanol induced tubal occlusion in nonhuman primates immunohistochemical detection of collagen i v
Contraception, 2016Co-Authors: Jeffrey T Jensen, S Yao, Ov D Slayden, Dong Ock LeeAbstract:Objective Intrauterine Administration of polidocanol foam (PF) can create fallopian tube occlusion in nonhuman primates. The objective of this study was to determine if PF-induced tubal obstructions contain collagen in the extracellular matrix.
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Intrauterine Administration of cdb 2914 ulipristal suppresses the endometrium of rhesus macaques
Contraception, 2010Co-Authors: Robert M Brenner, Ov D Slayden, Anita Nath, Yunyen Tsong, Regine SitrukwareAbstract:Abstract Background Ulipristal (UPA; CDB-2914) is a progesterone receptor modulator with contraceptive potential. To test its effects when delivered by an Intrauterine system (IUS), we prepared control and UPA-filled IUS and evaluated their effects in rhesus macaques. Study Design Short lengths of Silastic tubing either empty ( n =3) or containing UPA ( n =5) were inserted into the uteri of 8 ovariectomized macaques. Animals were cycled by sequential treatment with estradiol and progesterone. After 3.5 cycles, the uterus was removed. Results During treatment, animals with an empty IUS menstruated for a mean total of 11.66��0.88 days, while UPA-IUS treated animals bled for only 1��0.45 days. Indices of endometrial proliferation were significantly reduced by UPA-IUS treatment. The UPA exposed endometria were atrophied with some glandular cysts while the blank controls displayed a proliferative morphology without cysts. Androgen receptors were more intensely stained in the glands of the UPA-IUS treated endometria than in the blank-IUS treated controls. Conclusions In rhesus macaques, a UPA-IUS induced endometrial atrophy and amenorrhea. The work provides proof of principle that an IUS can deliver effective Intrauterine concentrations of Ulipristal.
Fuller W Bazer - One of the best experts on this subject based on the ideXlab platform.
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effects of the estrous cycle pregnancy and interferon tau on 2 5 oligoadenylate synthetase expression in the ovine uterus
Biology of Reproduction, 2001Co-Authors: Greg A Johnson, Fuller W Bazer, David M Stewart, Allison C Gray, Youngsok Choi, Robert C Burghardt, Liyuan Yulee, Thomas E SpencerAbstract:The enzymes which comprise the 29,59-oligoadenylate synthetase (OAS) family are interferon (IFN) stimulated genes which regulate ribonuclease L antiviral responses and may play additional roles in control of cellular growth and differentiation. This study characterized OAS expression in the endometrium of cyclic and pregnant ewes as well as determined effects of IFNt and progesterone on OAS expression in cyclic or ovariectomized ewes and in endometrial epithelial and stromal cell lines. In cyclic ewes, low levels of OAS protein were detected in the endometrial stroma (S) and glandular epithelium (GE). In early pregnant ewes, OAS expression increased in the S and GE on Day 15. OAS expression in the lumenal epithelium (LE) was not detected in uteri from either cyclic or pregnant ewes. Intrauterine Administration of IFNt stimulated OAS expression in the S and GE, and this effect of IFNt was dependent on progesterone. Ovine endometrial LE, GE, and S cell lines responded to IFNt with induction of OAS proteins. In all three cell lines, the 40/ 46-kDa OAS forms were induced by IFNt, whereas the 100-kDa OAS form appeared to be constitutively expressed and not affected by IFNt. The 69/71-kDa OAS forms were induced by IFNt in the S and GE cell lines, but not in the LE. Collectively, these results indicate that OAS expression in the endometrial S and GE of the early pregnant ovine uterus is directly regulated by IFNt from conceptus and requires the presence of progesterone. conceptus, cytokines, female reproductive tract, gene regulation, hormone action, implantation/early development, pregnancy, uterus
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effects of recombinant ovine interferon tau placental lactogen and growth hormone on the ovine uterus
Biology of Reproduction, 1999Co-Authors: Thomas E Spencer, Allison Gray, Greg A Johnson, Kristin M Taylor, Arieh Gertler, Elisha Gootwine, Troy L Ott, Fuller W BazerAbstract:Studies were conducted to determine effects of Intrauterine Administration of recombinant ovine interferon t (IFNt), placental lactogen (PL), and growth hormone (GH) on endometrial function. In the first study, Administration of IFNt to cyclic ewes for one period (Days 11‐15) resulted in an interestrous interval (IEI) of ;30 days, whereas Administration for two periods (Days 11‐15 and Days 21‐25) extended the IEI to greater than 50 days. Administration of IFNt from Days 11 to 15 and of PL or GH from Days 21 to 25 failed to extend the IEI more than for IFNt alone. In the second study, effects of IFNt, PL, and GH on endometrial differentiation and function were determined in ovariectomized ewes receiving ovarian steroid replacement therapy. Endometrial expression of mRNAs for estrogen receptor (ER), progesterone receptor (PR), and oxytocin receptor (OTR) were not affected by PL or GH treatment; however, uterine milk protein mRNA levels and stratum spongiosum gland density were increased by both PL and GH treatments. Collectively, results indicated that 1) PL and GH do not regulate endometrial PR, ER, and OTR expression or affect corpus luteum life span; 2) down-regulation of epithelial PR expression is requisite for progesterone induction of secretory gene expression in uterine glandular epithelium; 3) effects of PL and GH on endometrial function require IFNt; and 4) PL and GH regulate endometrial gland proliferation and perhaps differentiated function.
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differential effects of Intrauterine and subcutaneous Administration of recombinant ovine interferon tau on the endometrium of cyclic ewes
Biology of Reproduction, 1999Co-Authors: Thomas E Spencer, Greg A Johnson, Troy L Ott, A G Stagg, W S Ramsey, Fuller W BazerAbstract:Interferon tau (IFNtau) is the antiluteolytic signal produced by the conceptus of ruminants. Intrauterine Administration of recombinant ovine IFNtau suppresses expression of endometrial estrogen receptor (ER) and oxytocin receptor (OTR) in the luminal and superficial glandular epithelia to abrogate the production of luteolytic prostaglandin F(2alpha) (PGF(2alpha)) pulses. Subcutaneous (s.c.) injections of recombinant ovine (o) IFNtau appear to extend the interestrous interval by altering uterine PGF(2alpha) response to oxytocin. The present study tested the hypothesis that antiluteolytic effects of roIFNtau injected into the uterine lumen (paracrine) or s.c. (endocrine) are equivalent in suppressing expression of endometrial ER and OTR and inducing uterine expression of type I IFN-regulated Mx and ubiquitin cross-reactive proteins (UCRP). Sixteen cyclic ewes were fitted with uterine catheters on Day 5 (Day 0 = estrus), were assigned randomly to receive treatment with control proteins or roIFNtau (2 x 10(7) antiviral units/day) by either Intrauterine or s.c. injections from Days 11 to 15, and were ovariohysterectomized on Day 16. Results indicated that expression of ER and OTR mRNAs in endometrial epithelium was suppressed by Intrauterine but not by s.c. injections of roIFNtau. Intrauterine injections of roIFNtau increased expression of Mx and UCRP mRNA in the endometrium. Subcutaneous injections of roIFNtau increased endometrial Mx mRNA levels but not UCRP mRNA. Unexpectedly, Intrauterine and s.c. injections of roIFNtau were equally effective in inducing expression of Mx and UCRP mRNA in the corpus luteum. Although s.c. injections of roIFNtau induced Mx mRNA in the endometrial epithelium, s.c. injections of roIFNtau did not abrogate activation of the uterine luteolytic mechanism by suppressing epithelial ER and OTR expression. Therefore, results of this study failed to support the assumption that endocrine roIFNtau mimics antiluteolytic effects of paracrine IFNtau to improve pregnancy rates in sheep.
Thomas E Spencer - One of the best experts on this subject based on the ideXlab platform.
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effects of the estrous cycle pregnancy and interferon tau on 2 5 oligoadenylate synthetase expression in the ovine uterus
Biology of Reproduction, 2001Co-Authors: Greg A Johnson, Fuller W Bazer, David M Stewart, Allison C Gray, Youngsok Choi, Robert C Burghardt, Liyuan Yulee, Thomas E SpencerAbstract:The enzymes which comprise the 29,59-oligoadenylate synthetase (OAS) family are interferon (IFN) stimulated genes which regulate ribonuclease L antiviral responses and may play additional roles in control of cellular growth and differentiation. This study characterized OAS expression in the endometrium of cyclic and pregnant ewes as well as determined effects of IFNt and progesterone on OAS expression in cyclic or ovariectomized ewes and in endometrial epithelial and stromal cell lines. In cyclic ewes, low levels of OAS protein were detected in the endometrial stroma (S) and glandular epithelium (GE). In early pregnant ewes, OAS expression increased in the S and GE on Day 15. OAS expression in the lumenal epithelium (LE) was not detected in uteri from either cyclic or pregnant ewes. Intrauterine Administration of IFNt stimulated OAS expression in the S and GE, and this effect of IFNt was dependent on progesterone. Ovine endometrial LE, GE, and S cell lines responded to IFNt with induction of OAS proteins. In all three cell lines, the 40/ 46-kDa OAS forms were induced by IFNt, whereas the 100-kDa OAS form appeared to be constitutively expressed and not affected by IFNt. The 69/71-kDa OAS forms were induced by IFNt in the S and GE cell lines, but not in the LE. Collectively, these results indicate that OAS expression in the endometrial S and GE of the early pregnant ovine uterus is directly regulated by IFNt from conceptus and requires the presence of progesterone. conceptus, cytokines, female reproductive tract, gene regulation, hormone action, implantation/early development, pregnancy, uterus
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effects of recombinant ovine interferon tau placental lactogen and growth hormone on the ovine uterus
Biology of Reproduction, 1999Co-Authors: Thomas E Spencer, Allison Gray, Greg A Johnson, Kristin M Taylor, Arieh Gertler, Elisha Gootwine, Troy L Ott, Fuller W BazerAbstract:Studies were conducted to determine effects of Intrauterine Administration of recombinant ovine interferon t (IFNt), placental lactogen (PL), and growth hormone (GH) on endometrial function. In the first study, Administration of IFNt to cyclic ewes for one period (Days 11‐15) resulted in an interestrous interval (IEI) of ;30 days, whereas Administration for two periods (Days 11‐15 and Days 21‐25) extended the IEI to greater than 50 days. Administration of IFNt from Days 11 to 15 and of PL or GH from Days 21 to 25 failed to extend the IEI more than for IFNt alone. In the second study, effects of IFNt, PL, and GH on endometrial differentiation and function were determined in ovariectomized ewes receiving ovarian steroid replacement therapy. Endometrial expression of mRNAs for estrogen receptor (ER), progesterone receptor (PR), and oxytocin receptor (OTR) were not affected by PL or GH treatment; however, uterine milk protein mRNA levels and stratum spongiosum gland density were increased by both PL and GH treatments. Collectively, results indicated that 1) PL and GH do not regulate endometrial PR, ER, and OTR expression or affect corpus luteum life span; 2) down-regulation of epithelial PR expression is requisite for progesterone induction of secretory gene expression in uterine glandular epithelium; 3) effects of PL and GH on endometrial function require IFNt; and 4) PL and GH regulate endometrial gland proliferation and perhaps differentiated function.
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differential effects of Intrauterine and subcutaneous Administration of recombinant ovine interferon tau on the endometrium of cyclic ewes
Biology of Reproduction, 1999Co-Authors: Thomas E Spencer, Greg A Johnson, Troy L Ott, A G Stagg, W S Ramsey, Fuller W BazerAbstract:Interferon tau (IFNtau) is the antiluteolytic signal produced by the conceptus of ruminants. Intrauterine Administration of recombinant ovine IFNtau suppresses expression of endometrial estrogen receptor (ER) and oxytocin receptor (OTR) in the luminal and superficial glandular epithelia to abrogate the production of luteolytic prostaglandin F(2alpha) (PGF(2alpha)) pulses. Subcutaneous (s.c.) injections of recombinant ovine (o) IFNtau appear to extend the interestrous interval by altering uterine PGF(2alpha) response to oxytocin. The present study tested the hypothesis that antiluteolytic effects of roIFNtau injected into the uterine lumen (paracrine) or s.c. (endocrine) are equivalent in suppressing expression of endometrial ER and OTR and inducing uterine expression of type I IFN-regulated Mx and ubiquitin cross-reactive proteins (UCRP). Sixteen cyclic ewes were fitted with uterine catheters on Day 5 (Day 0 = estrus), were assigned randomly to receive treatment with control proteins or roIFNtau (2 x 10(7) antiviral units/day) by either Intrauterine or s.c. injections from Days 11 to 15, and were ovariohysterectomized on Day 16. Results indicated that expression of ER and OTR mRNAs in endometrial epithelium was suppressed by Intrauterine but not by s.c. injections of roIFNtau. Intrauterine injections of roIFNtau increased expression of Mx and UCRP mRNA in the endometrium. Subcutaneous injections of roIFNtau increased endometrial Mx mRNA levels but not UCRP mRNA. Unexpectedly, Intrauterine and s.c. injections of roIFNtau were equally effective in inducing expression of Mx and UCRP mRNA in the corpus luteum. Although s.c. injections of roIFNtau induced Mx mRNA in the endometrial epithelium, s.c. injections of roIFNtau did not abrogate activation of the uterine luteolytic mechanism by suppressing epithelial ER and OTR expression. Therefore, results of this study failed to support the assumption that endocrine roIFNtau mimics antiluteolytic effects of paracrine IFNtau to improve pregnancy rates in sheep.