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Shibuya-ku, Japan

Kawano N.,National Health Research Institute | Miyado K.,National Health Research Institute | Yoshii N.,Fertility Clinic Tokyo | Kanai S.,National Health Research Institute | And 6 more authors.
Scientific Reports | Year: 2014

In mammals, uterine epithelium is remodeled cyclically throughout adult life for pregnancy. Despite the expression of CD9 in the uterine epithelium, its role in maternal reproduction is unclear. Here, we addressed this issue by examining uterine secretions collected from patients undergoing fertility treatment and fertilization-competent Cd9-/- mice expressing CD9-GFP in their eggs (Cd9-/- TG). CD9 in uterine secretions was observed as extracellular matrix-like feature, and its amount of the secretions associated with repeated pregnancy failures. We also found that the litter size of Cd9 -/- TG female mice was significantly reduced after their first birth. Severely delayed re-epithelialization of the endometrium was then occurred. Concomitantly, vascular endothelial growth factor (VEGF) was remarkably reduced in the uterine secretions of Cd9-/- TG female mice. These results provide the first evidence that CD9-mediated VEGF secretion plays a role in re-epithelialization of the uterus. Source


Ouji-Sageshima N.,Nara Medical University | Yuui K.,Nara Medical University | Nakanishi M.,Nara Medical University | Takeda N.,Fertility Clinic Tokyo | And 9 more authors.
Journal of Reproductive Immunology | Year: 2016

In the field of in vitro fertilization (IVF), useful markers for the prediction of successful implantation for oocyte or embryo selection are essential. It has been reported that sHLA-G (sHLA-G1/HLA-G5) could be detected in the supernatant of the fertilized embryo and in follicular fluid samples (FFs), and that the presence of sHLA-G was related to successful implantation. If sHLA-G could be used as a marker of oocyte selection from multiple FFs, oocytes could be selected without physical contact, thus reducing the likelihood of damage. To investigate the potential for sHLA-G as a marker of oocyte selection from multiple FFs in one patient, protein levels of total protein, sHLA-G, and sHLA-I (sHLA-A, B, and C) were examined in FFs. The variation among multiple FFs in total protein level and sHLA-G level was not related to successful pregnancy. The average sHLA-I levels did not differ in the successful implantation and unsuccessful implantation groups, indicating that sHLA-I levels were not related to successful pregnancy. Furthermore, sHLA-G in FFs was not detected by western blotting, despite being detected by ELISA, while sHLA-I was detected by both ELISA and western blot. These data suggest that sHLA-G in FF might not be a useful marker for oocyte selection as measurements of sHLA-G were inconsistent and there was no association with successful pregnancy. Further, more rigorously tested ELISA systems for detecting sHLA-G in body fluids are necessary before the utility of sHLA-G for diagnosis can be established. © 2015 Elsevier Ireland Ltd. Source


Yoshii N.,Fertility Clinic Tokyo | Hamatani T.,Fertility Clinic Tokyo | Hamatani T.,Keio University | Inagaki N.,Saint Womens Clinic | And 6 more authors.
Reproductive Biology and Endocrinology | Year: 2013

Background: Recently, the concept of recurrent implantation failure (RIF) in assisted reproductive technology has been enlarged. Chronic uterine inflammation is a known cause of implantation failure and is associated with high matrix metalloproteinase (MMP) activity in uterine cavity flushing. MMP activity of women with RIF has been reported to be higher than that of fertile women. In the present retrospective study we evaluated the efficacy of treatment for high MMP activity in the uterine cavity of patients with RIF.Methods: Of the 597 patients recruited to the study, 360 patients underwent MMP measurements and 237 patients did not (control group). All patients had failed to become pregnant, despite at least two transfers of good-quality embryos. Gelatinase MMP-2 and MMP-9 activity in uterine flushing fluid was detected by enzymology (MMP test). All samples were classified into two groups (positive or negative) based on the intensity of the bands on the enzyme zymogram, which represents the degree of MMP activity. Patients who tested positive on the initial test were treated for 2 weeks with a quinolone antibiotic and a corticosteroid, and subsequently underwent a second MMP test. Negative results on the second MMP tests after treatment and subsequent rates of pregnancy and miscarriage were used to evaluate the efficacy of treatment. Data were analyzed by the Mann-Whitney U-test and the chi-square test.Results: Of the patients who underwent the MMP test, 15.6% had positive results (high MMP activity). After treatment, 89.3% of patients had negative results on the second MMP test. These patients had a significantly better pregnancy rate (42.0%) than the control group (26.6%), as well as a lower miscarriage rate (28.5% vs 36.5%, respectively).Conclusions: A 2-week course of antibiotics and corticosteroids effectively improves the uterine environment underlying RIF by reducing MMP activity. © 2013 Yoshii et al.; licensee BioMed Central Ltd. Source


Takeda N.,Fertility Clinic Tokyo | Takeda N.,Tohoku University | Yoshii N.,Fertility Clinic Tokyo | Hoshino Y.,Tohoku University | And 3 more authors.
Journal of Mammalian Ova Research | Year: 2012

Spermatozoa used for intracytoplasmic sperm injection (ICSI) are selected based on their motility and morphology. To explore other methods for selecting better spermatozoa, we developed a spermatozoa-sorting method using a physiologically natural selection system involving penetration into cervical mucus (CM). In addition, we analyzed the spermatozoa that penetrated the CM (CM-penetrating spermatozoa). The results were as follows. The CM-penetrating spermatozoa traveled a longer distance with better linear motility than spermatozoa in semen. Also, in comparison with spermatozoa obtained by density gradient centrifugation (DGC) and the swim-up method, the proportion of spermatozoa with normal morphology was higher, although, the proportion of spermatozoa with the head vacuole did not change. No DNA fragmentation was detected in the CM-penetrating spermatozoa. This method has several advantages. The technical procedure is simple and easy. Physical damage to spermatozoa is reduced because it does not require any centrifugation or washing procedure. A higher collection ratio of morphologically normal spermatozoon is achievable compared to the DGC and swim-up method, and it is a physiological selection method. We conclude that the CM penetration-based spermatozoa-sorting method is a promising new technique for ICSI because it is possible to collect physiologically better spermatozoa than those selected in the conventional selection method. © 2012 Japanese Society of Mammalian Ova Research. Source

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