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.
PMID 22951914 22951914 DOI 10.1093/humrep/des323 10.1093/humrep/des323 Kitaya et al. 2012, Kitaya 2012
Cite this article
Kitaya, K., Tada, Y., Taguchi, S., Funabiki, M., Hayashi, T., & Nakamura, Y. (2012). Local mononuclear cell infiltrates in infertile patients with endometrial macropolyps versus micropolyps.. Human reproduction (Oxford, England), 27(12), 3474-80. https://doi.org/10.1093/humrep/des323
Kitaya K, Tada Y, Taguchi S, Funabiki M, Hayashi T, Nakamura Y. Local mononuclear cell infiltrates in infertile patients with endometrial macropolyps versus micropolyps.. Human reproduction (Oxford, England). 2012;27(12):3474-80. doi:10.1093/humrep/des323
Are serum vitamin D levels associated with the incidence of endometrial polyps (EPs) in infertile patients? Serum 25(OH)D levels were nonlinearly correlated with the incidence of EPs in infertile women. EPs are a common condition that may affect the receptivity of the endometrium in women of reproductive age. Vitamin D regulates cell proliferation and differentiation, apoptosis, angiogenesis, anti-inflammation, and immunomodulation, in addition to its well-known functions in balancing calcium and phosphorus. Previous studies have shown that vitamin D concentrations are associated with reproductive outcomes, and that low vitamin D levels are associated with the incidence of colorectal polyps and nasal polyps. There is little evidence regarding the relationship between EPs and serum vitamin D levels. STUDY DESIGN, SIZE, We conducted a cross-sectional study using data from Guangdong Women and Children Hospital from January 2019 to October 2023, enrolling 3107 patients. PARTICIPANTS/MATERIALS, SETTING, A total of 3107 infertile patients who underwent hysteroscopy were included in this study; 642 patients had endometrial polyps and 2465 had a normal uterine cavity. Hysteroscopy findings included risk of EPs, polyp size, percentage of multiple polyps, and incidence of chronic endometritis (CE). Serum vitamin D were assessed by measuring total 25(OH)D using chemiluminescence. According to international guideline recommendations for vitamin D deficiency, patients were divided into two groups: the <50 nmol/l group and the ≥50 nmol/l group. Univariable and multivariable logistic regression models, stratified analyses, and smooth curve fitting were used to examine the relationship between serum 25(OH)D levels and risk of EPs. MAIN Of all patients, 23.8% (740/3107) were vitamin D deficient (<50 nmol/l). The incidence of EPs was significantly higher in the 25(OH)D < 50 nmol/l group than in the ≥50 nmol/l group (24.9% vs 19.3%; P = 0.001). However, there were no differences in polyp size, proportion of multiple polyps, and presence of CE between the two groups. After controlling for confounders, 25(OH)D ≥ 50 nmol/l (compared with <50 nmol/l) was negatively associated with risk of EPs (adjusted OR, 0.733; 95% CI, 0.598-0.898). Other variables that had an impact on polyp incidence included BMI, type of infertility, CA125, and CD138-positive plasma cells. In addition, a linear regression model between age and serum 25(OH)D levels showed a positive linear association. Subgroup analyses were performed for different age groups, and the risk of EPs was significantly higher in the 25(OH)D < 50 nmol/l group than in the ≥50 nmol/l group, both in the younger subgroup (23.8% vs 19.1%) and in the older subgroup (28.0% vs 19.9%). The smooth curve fitting model showed a nonlinear correlation between 25(OH)D levels and risk of EPs (nonlinear P-value = 0.020), with an optimal threshold of 51.8 nmol/l for 25(OH)D levels. Moreover, subgroup smooth curve fitting models showed a nonlinear correlation between 25(OH)D levels and polyp risk in patients aged <35 years (nonlinear P-value = 0.010), whereas a linear correlation between 25(OH)D levels and polyp risk was found in patients aged ≥35 years (nonlinear P-value = 0.682). LIMITATIONS, Caution should be exercised in interpreting our findings as this is a correlational study and causality cannot be inferred from our results. In addition, because of strict inclusion and exclusion criteria, our results may not be generalizable to unselected populations, including premenopausal women or women of other races. This study demonstrated for the first time that vitamin D deficiency is an independent risk factor for the incidence of EPs in infertile patients. Identifying modifiable risk factors (e.g. vitamin D deficiency) can help in the development of new strategies for treating polyps or to protect against polyp development. Further clinical intervention trials and laboratory studies are needed to evaluate the effect of vitamin D on the development of EPs and to elucidate the mechanisms. STUDY FUNDING/COMPETING INTEREST(S): The study was funded by the National Natural Science Foundation of China (82101718) and Natural Science Foundation of Guangdong Province, China (2022A1515010776). No competing interest was involved in this study. N/A.
Progesterone is a known immunosupressant in humans and may be important in treatment regimens for women with immunological and endocrinological reproductive failure. The molecular mechanism of progesterone-mediated immunosuppression remains controversial. We used the reverse transcriptase polymerase chain reaction (RT-PCR) technique to detect progesterone receptor RNA in human peripheral blood mononuclear cells (PBMCs). No expression could be documented in PBMCs from men or women representing various reproductive states. We also used the glucocorticoid receptor antagonist RU 43044 to address the hypothesis that progesterone exerts immunomodulatory effects via interactions with the glucocorticoid receptor. Both hydrocortisone (10(-6) and 10(-7) M) and progesterone (10(-5), 10(-6) and 10(-7) M) inhibited phytohaemagglutinin-induced lymphocyte proliferation in a dose-dependent fashion. RU 43044 (10(-5) M) significantly reversed the immunosuppressive effect od hydrocortisone but not that of progesterone. These studies indicate that human PBMCs do not express the classical progesterone receptor. Our results further suggest that progesterone does not mediate its immunomodulatory effects via interaction with the glucocorticoid receptor. Interaction with other members of the steroid and thyroid hormone receptor superfamily, local conversion to other steroid substances or non-classical receptor-mediated mechanisms may be involved.
Endometriosis is defined as the growth of endometrial glands and stromal cells in a heterotopic location with immune dysregulation. It usually leads to chronic pelvic pain and subfertility. Although various treatments are available, the recurrence rate remains high. Adipose tissue is an abundant source of multipotent mesenchymal adipose-derived stem cells (ADSCs). ADSCs display effects on not only tissue regeneration, but also immune regulation. Thus, the current study aims to test the effects of ADSCs on the growth of endometriosis. ADSCs isolated from lipoaspiration-generated adipose tissue and their conditioned medium (ADSC-CM) were subjected to quality validation, including karyotyping as well as growth promotion and sterility tests for microbial contamination under Good Tissue Practice and Good Manufacturing Practice regulations. An autologous endometriosis mouse model was established by suturing endometrial tissue to peritoneal wall followed by treating with DMEM/F12 medium, ADSC-CM, ADSCs or ADSC-CM+ADSCs for 28 days. The area of endometriotic cysts and the degree of pelvic adhesion were measured. ICAM-1, VEGF and caspase 3 expression was assessed by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and immunohistochemistry. Moreover, the mice were allowed to mate and deliver. The pregnancy outcomes were recorded. The ADSC-CM was subjected to proteomics analysis with further data mining with Ingenuity Pathway Analysis (IPA). Both ADSC-CM and ADSCs passed quality validation. ADSC-CM reduced the area of endometriotic cysts. The inhibition by ADSC-CM was obliterated by adding ADSCs. The presence of ADSCs with or without ADSC-CM increased the peritoneal adhesion. ADSC-CM inhibited ICAM-1 and VEGF mRNA and protein expression, whereas the addition of ADSCs not only did not inhibit by itself, but also blocked the inhibition by ADSC-CM. The resorption rate was reduced by ADSC-CM. The number of live birth/dam and the survival rate of pup at 1 week-old were both increased by ADSC-CM in mice with endometriosis. IPA demonstrated that PTX3 was potentially critical for the inhibition of endometriosis by ADSC-CM due to its anti-inflammatory and antiangiogenic properties as well as its importance in implantation. ADSC-CM inhibited endometriosis development and improved pregnancy outcomes in mice. Potential translation to clinical treatment for human endometriosis is expected.
Vitagliano A et al., 2021·Diagnostics (Basel)·
Open Access
Chronic endometritis (CE) and endometrial polyps (EPs) are common conditions in reproductive age women. CE is an infectious disorder of the endometrium characterized by signs of chronic inflammation at hysteroscopic and histological analyses. EPs are abnormal endometrial growths containing glands, stroma and blood vessels projecting from the lining of the uterus. During the last years, different authors have investigated the correlation between CE and EPs, with controversial results. The aim of this study was to summarize available evidence on the potential correlation between CE and EPs.
Systematic literature review and meta-analysis. Observational-studies were identified by searching electronic databases from their inception to September 2021. Only studies on pre-menopausal women were included. Statistical analysis was performed using MedCalc 16.4.3 (Ostend, Belgium) and Review Manager version 5.3 (Nordic Cochrane Centre, Cochrane Collaboration). The summary measures were reported as pooled proportion or odds ratio (OR) with 95% confidence interval (CI). The primary outcome was to evaluate the prevalence of CE in women with EPs. The secondary outcome was to determine the prevalence of CD-138-positive EPs among EPs. Tertiary outcomes were to compare the prevalence of CE in women with EPs versus women with a non-polypoid endometrium and to compare the prevalence of CE in women with a single EP versus women with multiple EPs. Eight observational studies (n = 3225 patients) were included in quantitative synthesis. Pooled prevalence of CE among women with EPs was 51.35% (95% CI, 27.24-75.13%). Pooled proportion of CD-138-positive EPs among EPs was 70.73% (95% CI, 55.73-83.68%). Women with EPs showed higher prevalence of CE compared to women without EPs (OR 3.07, 95% CI 1.59-5.95). Women with ≥3 EPs had higher prevalence of CE then women with a single EP (OR 3.43, 95% CI 1.83-6.46). In pre-menopausal women, CE and EPs may have a dependent relationship and may represent two consequent steps of a common pathological process.