Yoshihiro Tada

IL-15 Expression at Human Endometrium and Decidua

Abstract A large number of natural killer (NK) cells appear in human uterine mucosa during the secretory phase and first trimester pregnancy. We investigated the expression of interleukin (IL)-15, a possible stimulator for these NK cells, in human endometrium and first trimester decidua. Semiquantitative reverse transcriptase-polymerase chain reaction revealed that IL-15 mRNA expression was stronger during the secretory phase and first trimester pregnancy than during the proliferative phase. Immunohistochemistry revealed that immunoreactivity for anti-IL-15 was higher during the secretory phase than it was during the proliferative phase. This was prominent in the perivascular stromal cells around invading spiral arteries during the mid- to late-secretory phase. In first trimester decidua, endothelial cells were also stained as strongly as stromal cells. A membrane-bound IL-15 molecule was detected on the surface of first trimester decidual cells by flow cytometry. Progesterone stimulated the release of soluble IL-15 in the supernatant of cultured decidual cells. These results suggest that IL-15 expression in human uterine mucosa corresponds to the fluctuation of uterine NK cells and that its production is hormonally controlled, especially by progesterone.

Local mononuclear cell infiltrates in infertile patients with endometrial macropolyps versus micropolyps

STUDY QUESTION Is the endometrial mononuclear cell population in infertile patients altered in subjects with classical endometrial polyps (macropolyps) versus endometrial micropolyps that are hysteroscopically recognized as small uterine cavity protrusions? SUMMARY ANSWER Macropolypoid endometrium had a low density of pan-leukocytes, pan-T cells and natural killer (NK) cells, whereas micropolypoid endometrium was characterized by high density of B cells and plasmacytes, along with a low density of NK cells. WHAT IS KNOWN ALREADY Endometrial micropolyps co-exist at a high rate with chronic endometritis, which is an unusual plasmacyte infiltration within the endometrial stromal compartment. STUDY DESIGN Prospective cross-sectional study. From July 2009 to June 2011, hysteroscopy was performed for infertile women who had been suspected for endometrial macropolyps and who had repeated in vitro fertilization-embryo transfer failure over three or more cycles. Endometrial biopsy samples were obtained from the patients with macropolyps or micropolyps during the proliferative phase. Of 137 patients assessed, 30 were diagnosed with endometrial macropolyps and 34 were diagnosed with endometrial micropolyps. After the exclusion of the cases with heavy uterine bleeding, potential neoplasms, submucosal uterine fibroids, uterine septa, and/or intrauterine adhesion, 23 patients with macropolypoid endometrium; 25 patients with micropolypoid endometrium and 27 patients with non-polypoid endometrium were enrolled in the study. Endometrial macropolyps were surgically removed, whereas chronic endometritis was treated with antibiotics. The patients were followed up until December 2011. PARTICIPANTS/MATERIALS, SETTING, METHODS The paraformaldehyde-fixed paraffin-embedded endometrial sections were immunostained with monoclonal antibodies against the specific markers of pan-leukocytes (CD45), pan-T cells (CD3), Th cells (CD4), Tc cells (CD8), B cells (CD20), plasmacytes (CD138), NK cells (CD56) and macrophages (CD68). The immunoreactive cells were enumerated in at least 20 non-overlapping stromal areas. MAIN RESULTS AND THE ROLE OF CHANCE Compared with the non-polypoid endometrium, macropolypoid endometrium contained a lower density of pan-leukocytes, pan-T cells and NK cells, whereas micropolypoid endometrium had a higher density of pan-leukocytes and B cells, along with a lower density of NK cells. Following the treatments, 10 patients with macropolypoid endometrium, 11 patients with micropolypoid endometrium and 10 patients with non-polypoid endometrium conceived. LIMITATIONS, REASONS FOR CAUTION One potential bias is immunohistochemical enumeration for leukocyte density was conducted by one examiner. The limitation of this study is that the results relied on endometrial biopsy specimens, of which immunological conditions may not always represent those in the whole endometrium. WIDER IMPLICATIONS OF THE FINDINGS There may be some ethnic or racial variances in the composition of the endometrial mononuclear cell subsets of infertile women. STUDY FUNDING/COMPETING INTEREST(S) This study was supported by Grand-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology (22591840). There were no conflicts of interest to declare.

Comprehensive Endometrial Immunoglobulin Subclass Analysis in Infertile Women Suffering from Repeated Implantation Failure with or without Chronic Endometritis

Chronic endometritis (CE) is a local inflammatory condition with unusual plasmacyte infiltration in the endometrial stromal area. CE is frequently found in infertile women with repeated implantation failure (RIF). In this study, we comprehensively investigated the endometrial immunoglobulin (Ig) subclass expression in infertile women suffering from RIF with versus without CE.

Unusual inflammation in gynecologic pathology associated with defective endometrial receptivity.

Human cycling endometrium displays a series of periodic transitions unique to this mucosal tissue, which includes rapid proliferation, secretory transformation, physiological angiogenesis, interstitial edema, and menstrual shedding. Among these properties of the endometrium are the inflammatory changes that occur dynamically across the menstrual cycle. Immunocompetent cell composition and inflammatory gene expression pattern in the human endometrium drastically fluctuate from the proliferative phase to the secretory phase, particularly at the time of ovulation. These local immune responses are fine-tuned by the direct or indirect action of two representative ovarian steroids, estradiol and progesterone, and are essential for successful blastocyst implantation. Meanwhile, studies have been accumulating the evidence that such physiological endometrial inflammatory status is altered in the presence of certain gynecologic pathologies. Given that blastocysts are semi-allografts for maternal tissue, even subtle alterations in endometrial immunity potentially have a negative impact on implantation process. In this article, we aimed to review and discuss the physiological and pathological mucosal inflammatory conditions that can affect endometrial receptivity.

Diverse functions of uterine proteoglycans in human reproduction (Review)

Proteoglycans (PGs) are a group of heavily glycosylated proteins that are present throughout the mammalian body and are involved in a wide variety of biological phenomena, including structural maintenance, tissue remodeling, molecular presentation, cell adhesion and signal transmission. Previous studies have revealed an increasing number of roles for PGs in human reproduction. Several PGs are currently utilized or regarded as biomarkers for the diagnosis of certain pathological uterine conditions associated with infertility and obstetrical complications. The aim of this review was to discuss the involvement of PGs in the human uterus in reproductive biology and pathophysiology.

Low follicular fluid tyrosine concentration in infertile women with ovarian hyperstimulation syndrome

The aim of this study was to compare the branched-chain amino acid (BCAA) and tyrosine concentration in the follicular fluid of infertile women with and without ovarian hyperstimulation syndrome (OHSS) in an in vitro fertilization program combined with controlled ovarian stimulation. Follicular fluid was aspirated during oocyte retrieval from 20 infertile patients who developed moderate-to-severe OHSS and 20 age- and body mass index-matched normoresponders. BCAA and tyrosine concentration were measured using enzymatic methods. The follicular fluid BCAA concentration was similar between the two groups (P=0.55), whereas tyrosine concentration was significantly lower in the OHSS compared to that in the normoresponder group (P=0.027) and the BCAA/tyrosine ratio was significantly higher in the OHSS compared to that in the normoresponder group (P=0.034). These results suggest an association between low follicular fluid tyrosine concentration and OHSS. Dopamine receptor agonists may be used as potential anti-OHSS medicines and tyrosine, as a dopamine precursor, may play a role against the development of OHSS.

Occurrence of Multinucleated Embryos After Intra-Cytoplasmic Sperm Injection Treatment May Be Prevented by the Administration of Prednisolone

The occurrence of multinucleated embryos after intra-cytoplasmic sperm injection (ICSI) treatment may be prevented by the administration of prednisolone. J Med Cases. 2018;9(2):52-53 doi: https://doi.org/10.14740/jmc2986w