Endometrial Surface Epithelium Research Articles

Case Report of Lipomyoma

Report: Uterine lipoleiomyoma are rare forms of leiomyomas that are often only described in literature as case reports. Lipoleiomyomas could increase in size despite menopause and most commonly occur in postmenopausal women with an incidence rate of 0.03% to 0.2% Clinical symptoms of lipoleiomyoma are very similar to leiomyoma. Radiologic imaging can aid in the diagnosis of lipoleiomyoma with smooth muscle confined to the tumor periphery. In our case, we describe a 53y/o G0P0 perimenopausal patient who complained of abnormal uterine bleeding with irregular menses, urinary retention and difficulty completely emptying her bladder due to the large mass compressing her bladder. She was diagnosed with a large 8.8 cm hyperechoic lesion with internal vascularity arising from the central uterus/ endometrium. Radiology recommended a pelvic MRI for further differentiation of mass. Office hysteroscopy with endometrial biopsy was performed. Pathology confirmed limited inactive endometrium, benign endometrial surface epithelium. The patient requested a hysterectomy through a minimally invasive gynecologic surgery approach. A pelvic MRI was performed that revealed a large, round, circumscribed mass measuring 7.3 X 7.2 X 7.5 cm favoring to represent an intramural lipoleiomyoma. The patient had a robotic assisted laparoscopic hysterectomy which was uncomplicated. Final histopathologic diagnosis was uterine lipomyoma. As benign masses, management for lipoleiomyoma are guided by symptoms, fertility preservation desires, and whether or not a patient is a candidate for surgical intervention. Given the rarity of these cases, the histogenesis is still relatively unknown although various theories exist such as differentiation of embryonic fat cells, metaplastic changes of existing cells into fat cells, and pluripotent cell migration. Although there was not evidence of malignancy in our case report, certain literature has suggested the presence of coexisting malignancies and in an even rarer occasion the presence of liposarcoma from a lipoleiomyoma. More information is needed on these rare cases in order to further lead management and any recommendations regarding cancer screening on top of age related recommendations already in place.

COMPARISON BETWEEN VARIOUS METHODS OF MANAGEMENT OF UTERINE POLYP AND TO FIND OUT THE MOST EFFECTIVE AND SAFE METHOD

Endometrial polyp are soft, fleshy intrauterine growths are composed of endometrial glands, fibrous stroma, and surface epithelium. Prevalence inthe general population approximates 9 percent. Various modalities are available for the management of endometrial polyp. We conducted this study to compare between D & C,Hysteroscopic scissors and forceps, Monopolar Cautery with Glycine, Bipolar Cautery with normal saline as methods for polypectomy.

Histopathological Evaluation of Endometrial Biopsies in Different Age Groups: A Tertiary Care Experience in Turkey

Background: An endometrial biopsy primarily aims to determine endometrial cancer and hyperplasia with atypia at an early stage. Objectives: This study aims to evaluate the indications, histopathological diagnoses, and the number of endometrial biopsies performed in our clinic, according to the age groups of patients, in light of the literature. Methods: A retrospective review was conducted on the file data of 4,965 patients who underwent endometrial biopsy for non-obstetric reasons between 2014-2021. The patients were divided into five groups, according to their age. Pathology diagnoses were classified as benign endometrial pathology, premalignant-malignant pathology, and insufficient for diagnosis. Results: The most common biopsy indication was abnormal uterine bleeding (61.9%), while the most common histopathological result was benign endometrial pathologies (75.3%). Endometrial cancer was also detected in 3% of the patients. The highest diagnosis of benign endometrial pathology among age groups was 96.6% in those below 35. The comparison of age groups in the diagnosis of premalignant-malignant pathology revealed that the highest diagnosis rate was 32.1% in those 65 years and over. Furthermore, the evaluation of the relationship between indications and material adequacy showed that the highest rate of insufficient for diagnosis pathology was in the postmenopausal patient group (34.0%). Moreover, insufficient for diagnosis and endometrial surface epithelium results were highest in patients over 65 (46.7%). Conclusion: Patients aged 55-64 and those over 65 had the highest rate of endometrial cancer and insufficient for diagnosis biopsy results. Therefore, dilation and curettage may be recommended while taking a biopsy from patients in this age group.

Ulipristal Asetatın Ratlarda Oluşturulan Cerrahi Endometriozise Etkisi

Objective: The effect of Ulipristal Acetate on endometriosis foci created in rats was investigated. Methods: The study was conducted with 12-week-old rats weighing approximately 280 grams. After creating an autologous endometriosis model, the group that did not receive ulipristal acetate negative was administered with oral saline daily, and the group given ulipristal acetate positive was administered with 0.5 mg/kg (0.125 mg/rat/day) orally for 4 weeks. Ectopic endometrial tissues were removed for histopathological and immunohistochemical evaluations. Staining was performed with Hematoxylin Eosin, Ki-67, and Cyclooxygenase-2. Results: The Hematoxylin-Eosin Staining score of the ectopic endometrium surface epithelium was found to be 2.5 points in the ulipristal acetate negative group, and 0.5 points in the ulipristal acetate positive group. In the immunohistochemical evaluation, Ki-67 positivity of the ectopic endometrial surface epithelium was found to be 71.2% in the ulipristal acetate negative group vs. 31.7% in the ulipristal acetate positive group. Cyclooxygenase-2 positivity was detected as 67% in the ulipristal acetate negative group vs. 27% in the ulipristal acetate positive group. Conclusions: Hematoxylin-Eosin staining revealed that ulipristal acetate negative group was 2.5 (well-moderately preserved epithelium), and the ulipristal acetate positive group was 0.5 (epithelium was rarely present or absent). It was found that the percentage of Ki-67 and Cyclooxygenase-2 immunohistochemical positivity was decreased in the ulipristal acetate positive group compared to the ulipristal acetate negative group at a statistically significant level. More literature data are needed on this subject.

Evaluation of glycan expression in endometrial epithelial structures as a predictive factor for endometrial receptivity

Aim. To evaluate the endometrial glyotype in the implantation window in patients with infertility in assisted reproductive technologies (ART) programs and to develop criteria for assessing endometrial receptivity based on the analysis of complex changes in the functional groups of glycans in the main endometrial epithelial to use in clinical practice.
 Materials and methods. The study included 32 infertile patients who took part in ART programs. Pipelle endometrial biopsy was performed during the implantation window in the cycle preceding the cycle of ovarian stimulation and embryo transfer. Using lectin histochemistry and immunohistochemistry, glycans levels in the glycocalyx of endometrial surface epithelium (SE) and glandular epithelium (GE) was studied.
 Results. Differences in the expression of mannose-rich glycans in SE and N-acetylgalactosamine--terminated glycans in the GE of the endometrium were revealed, as well as the link between the expression of lectin staining glycans: ConA, VVL, UEA-I, SNA, MAL-II, ECL and monoclonal antibodies: anti-MECA -79 mAb and anti-LeY mAb in SE and GE of the endometrium was assessed in patients with infertility, depending on the outcome of the ART program. The estimated threshold levels in glycan expression and the odds ratio for pregnancy occurrence allow to characterize the diagnostic value for the studied glycomarkers and to develop criteria for assessing endometrial receptivity.
 Conclusion. Based on a comprehensive evaluation of glycans in the main endometrial epithelial structures in the cycle preceding the ART cycle, criteria for assessment of the likelihood of pregnancy have been developed, which can increase the effectiveness of ART programs in patients with infertility.

Design, synthesis, and biological evaluation of new raloxifene analogues of improved antagonist activity and endometrial safety

Raloxifene agonism of estrogen receptor (ER) in post-menopausal endometrium is not negligible. Based on a rational drug design workflow, we synthesized 14 analogues of raloxifene bearing a polar group in the aromatic ring of the basic side chain (BSC) and/or changes in the bulkiness of the BSC amino group. Analogues with a polar BSC aromatic ring and amino group substituents of increasing volume displayed increasing ER antagonism in Ishikawa cells. Analogues with cyclohexylaminoethoxy (13a) or adamantylaminoethoxy BSC (13b) lacking a polar aromatic ring displayed high ER-binding affinity and ER antagonism in Ishikawa cells higher than raloxifene and similar to fulvestrant (ICI182,780). The endometrial surface epithelium of immature female CD1 mice injected with 13b was comparable to that of vehicle-treated mice, while that of mice treated with estradiol, raloxifene or 13b in combination with estradiol was hyperplastic. These findings indicate that raloxifene analogues with a bulky BSC amino group could provide for higher endometrial safety treatment of the menopausal syndrome.

Synovial Metaplasia of the Endometrium

Abstract Introduction/Objective Synovial-like metaplasia is well known to accompany breast implants, but it can also rarely be found in the endometrium, associated with intrauterine devices. We present two cases of endometrial synovial-like metaplasia. Methods The hysterectomy specimens were diagnosed at Northwell Health and reviewed at the departmental Consensus Conference. Immunostains for cytokeratin AE1/AE3 were performed on the endometrium. The histopathologic findings were correlated with the clinical information. Results Both patients had had intrauterine devices placed for birth control. One, a 47-year-old female with a family history of Lynch syndrome and newly diagnosed with a corresponding mutation, underwent prophylactic hysterectomy. The second patient, a 50-year-old female with a history of uterine prolapse, was experiencing stress urinary incontinence, for which she underwent supracervical hysterectomy. Both patients had intrauterine devices in place at the time of hysterectomy. Both uteri showed endometrial synovial-like metaplasia. It was associated with a complete absence of the endometrial surface epithelium. The synovial-like cells were eosinophilic, plump and elongated, were palisaded perpendicular to the endometrial surface and were negative for cytokeratin AE1/AE3, which immunostain also confirmed the absence of the endometrial surface epithelium and the presence of some residual deeper endometrial glands. Conclusion Endometrial synovial-like metaplasia is a rare entity described in patients with intrauterine devices. The mesodermal-derived endometrium is apparently able, when exposed to a semi-mobile foreign body, to develop a way to minimize friction by mimicking synovium, similar to the connective tissue facing breast implants. Such surface must be better at withstanding chronic friction than the regular endometrial epithelial surface, leading to this unusual and fascinating change. Since the resulting surface mimics synovium perfectly, both morphologically and immunohistochemically, and serves a very similar mechanical purpose, we propose to call this phenomenon, wherever it is found, “synovial metaplasia” instead of the current term “synovial-like metaplasia.”

Ultrastructural markers of tissue endometrial receptivity in patients with recurrent implantation failure

The scanning electron microscopy of the endometrial surface epithelium during the ‘implantation window’ was performed in 119 patients with uterine factor of infertility or recurrent miscarriage due to endometrial hypoplasia. Ultramorphological picture of the surface endometrial epithelium was characterized by aplasia and hypoplasia of pinopodes (67.39%), dense cell – cell contacts (69.53%), heteromorphy of secretory cells (15.22%) in combination with atypia of microenvironment cells (50%) in patients with infertility. The asynchronous development of pinopodes (46.67%) and the absence of intercellular contacts separation during the ‘implantation window’ (84.44%) was observed in patients with recurrent miscarriage. The revealed disturbance determines the mechanisms of the blastocyst adhesion violation and trophoblast invasion in the different stages of implantation in patients with uterine factor of infertility and recurrent miscarriage.

Bisphenol S increases EZRIN expression and the detrimental effects induced by dehydroepiandrosterone in rat endometrium

The use of Bisphenol S (BPS) was proposed as an alternative to Bisphenol A (BPA), a chemical employed in the production of polycarbonate plastics and epoxy resins. BPA is a xenoestrogen that affects normal physiology in several species. It was reported that BPS may also act as a xenoestrogen with harmful effects in the reproductive system. Here we studied the effects of BPS during the induction of a polycystic ovarian syndrome (PCOS)-like condition in rats. Animals were injected daily with vehicle, DHEA 60 mg/kg, BPS 1 μg/kg and DHEA-BPS, for 20 days. Cell apoptosis, cell proliferation, and EZRIN expression were analyzed by immunohistochemistry. We found an increase in PCNA expression, which correlates with cytoplasmic accumulation of the polarization marker, EZRIN, in the BPS treated groups. Additionally, the administration of BPS in the DHEA treated group augmented the stratification and number of “intraepithelial lumina” in the endometrial surface epithelium.

Endometrial morphological characteristics in patients with hysteromyoma and chronic endometritis in infertility

To characterize endometrial structural and functional state and receptivity in women with hysteromyoma (HM) and chronic endometritis (CE) in infertile couples. A total of 130 patients who had HM and/or CE in an infertile couple were examined. Group 1 included 64 women with HM and CE; Group 2 consisted of 24 patients with HM; group 3 comprised 42 patients with EC. A control group included endometrial biopsy specimens from 20 healthy women planning a pregnancy. Patients with HM and CE were found to develop endometrial dysfunction. Its structural signs were damage to the endometrial surface epithelium; intense stromal fibrosis with the high expression of type III and IV collagens; dysregulated processes of high angiogenesis; impaired maturation of pinopodia by the implantation window; high estrogen receptor (ER) expression in the nuclei of endometrial glandular and stromal cells; low progesterone receptor (PR) expression; and impaired secretory endometrial transformation. HM concurrent with CE is responsible for endometrial dysfunction. Its structural manifestations are mainly associated with CE.

Activity of nucleolar organizers in endometrial glandular and surface epithelial cells in patients with external genital endometriosis

Hypothesis/aims of study. Endometriosis is a disease characterized by proliferation of tissue that is similar in morphology and function to the endometrium, outside the uterine cavity. Thanks to the theory of J. Sampson (1927), which explains endometrioid heterotopia formation by bits of endometrial tissue migrating through the fallopian tubes during menstruation and their subsequent implantation in the pelvis, research has begun on the biological properties of eutopic endometrial cells in women with endometriosis, which is still relevant today. The present study was aimed to assess the activity of nucleolus organizers in the endometrium in women with external genital endometriosis and without it at different stages of the menstrual cycle.
 Study design, materials, and methods. Paraffin blocks of endometrial biopsy specimens were taken from 68 women with and without external genital endometriosis. The activity of nucleolar organizers was evaluated by the method of J. Crocker (1983).
 Results. The data obtained showed a significant increase in ribosomal activity in the cells of the endometrial glandular and surface epithelium in women with external genital endometriosis at the stages of late proliferation, as well as early and middle secretions. There was also a significant decrease in the activity of the nucleolar organizers of endometrial epithelial cells at the stage of late secretion in women with external genital endometriosis.
 Conclusion. The obtained differences in regulation of ribosomal synthesis in the cells of the integument and glandular epithelium of the endometrium in women with external genital endometriosis, in our opinion, can provide an increase in the total amount of epitheliocytes of the endometrium, increase their adhesive and invasive abilities, and lengthen the life cycle of cells. This contributes to the formation of endometrioid heterotopies and the development of external genital endometriosis. Changes in the activity of nucleolar organizers in the endometrium in women with external genital endometriosis may be of clinical interest for the diagnosis of this pathology.

Unusual Case of Involvement of the Whole Uterus in Stage I Cervical Cancer: A Case Report

We report a case of squamous cell carcinoma of the uterine cervix in which the endocervical epithelium, endometrial surface epithelium, and uterine serosa were free from tumor, despite tumoral invasion of the entire thickness of the myometrium along the entire wall of the uterus. Although it has long been known that local tumor spread includes direct invasion of the parametrium and endometrial cavity with invasion of the underlying myometrium, in this case there was no tumoral involvement in endometrial cavity. In addition, there was no tumoral invasion or metastasis outside the uterus. To the best of our knowledge, uterine-wall invasion in this type of cervical squamous cell carcinoma has not been described in the literature so far.

Endometrial histopathology results and evaluation of endometrial cancer risk in geriatric women.

The incidence of premalignant and malignant endometrial disorders increases during the postmenopausal period. In the literature, endometrial disorders are usually discussed in the context of menopausal status. But there are limited data regarding endometrial disorders in geriatric patients. Early diagnosis of endometrial cancers with aggressive behaviour that increases during the geriatric period may allow simpler treatment options and also decrease the treatment-associated morbidity risk.Records of geriatric patients who underwent an endometrial histopathological evaluation between 2011 and 2016 were evaluated. Clinical findings, transvaginal ultrasonography findings, endometrial sampling methods, and histopathological results were evaluated.A total of 188 patients were included in the study (mean age 70.3 ±5.6 years). The most common histopathological results were endometrial polyp, atrophic endometrium, and surface epithelium (26.6%, 22.3%, and 12.8%, respectively). None of the 57 patients without vaginal bleeding had endometrial cancer. In 131 patients with vaginal bleeding, mean endometrial thickness was 9.8 ±8.1 mm (2-49 mm) and the rate of endometrial disorders was 56.5% (74 patients). Endometrial cancer was diagnosed in 19 patients (10.1%), and 36.8% of them had non-endometrioid cancers. The presence of vaginal bleeding was significantly associated with the diagnosis of endometrial cancer and any endometrial disorder (p = 0.001 and p = 0.000, respectively).The incidence of non-endometrioid endometrial cancers increased in the geriatric period. An endometrial histopathological examination should be considered, especially for patients with a history of vaginal bleeding. Further investigation of the endometrial thickness cut-off levels in the geriatric period will contribute to the literature.

The effects of intrauterine infusion of peanut oil on endometrial health, salivary cortisol and interovulatory period in mares

Intrauterine infusion of peanut oil at Day 10 post-ovulation has been reported to prolong dioestrus in mares. However, the effects of peanut oil treatment on the endometrium and whether the technique is painful have not been assessed. The objectives of this study were, (i) to determine the effect of intrauterine infusion of peanut oil on endometrial health, (ii) to determine whether use of intrauterine peanut oil is painful and (iii) to confirm that peanut oil causes prolonged dioestrus. Six mares aged 3–12 years old were used in a cross-over design with each mare administered both 1 ml of intrauterine peanut oil and a sham treatment on different oestrous cycles. The effect of intrauterine infusion of 1 ml peanut oil or sham treatment were measured using interovulatory period, uterine fluid accumulation as determined by transrectal ultrasonography, serum progesterone levels, endometrial Kenney biopsy scores and histological features, endometrial eosinophil numbers and salivary cortisol measurements. The individual mare response to intrauterine infusion of peanut oil was variable. Peanut oil infusion did not statistically prolong the luteal phase, nor elevate salivary cortisol levels but did cause superficial erosion of the endometrial surface epithelium in all mares and significantly increased eosinophil numbers in the endometrium (P = 0.0068). The Kenney grade for biopsies from 2/6 mares worsened transiently following infusion. In conclusion, intra-uterine peanut oil does not statistically increase the duration of the luteal phase but results in an inflammatory response and increase in endometrial eosinophil numbers suggesting treatment may be associated with a hypersensitivity-type reaction. Those contemplating using peanut oil to suppress oestrus should also be aware of the legislative and regulatory implications.

Reprogramming of the retinoic acid pathway in decidualizing human endometrial stromal cells.

Upon breaching of the endometrial surface epithelium, the implanting embryo embeds in the decidualizing stroma. Retinoic acid (RA), a metabolite of vitamin A, is an important morphogen during embryonic and fetal development, although the role of the RA pathway in the surrounding decidual cells is not understood. Here we show that decidual transformation of human endometrial stromal cells (HESCs) results in profound reprogramming of the RA signaling and metabolism pathways. Differentiating HESCs downregulate the intracellular carrier proteins CRABP2 and FABP5, responsible for transfer and binding of RA to the nuclear receptors RAR and PPARβ/δ, respectively. Furthermore, the expression of RAR, the receptor that mediates the pro-apoptotic effects of RA, was also inhibited. By contrast, PPARβ/δ, which transduces the differentiation responses of RA, was upregulated. Decidualization was also associated with increased expression of retinol-binding protein 4 (RBP4) and various enzymes involved in the metabolism of RA and its precursor, retinaldehyde (Rald), including CYP26A1, DHRS3, and RDH12. Exposure of differentiating HESCs to RA or Rald reversed the inhibition of the CRABP2-RAR pathway, perturbed the expression of decidual marker genes and triggered cell death. Taken together, the data demonstrate that decidualizing HESCs silence RA signaling by downregulating key cytoplasmic binding proteins and by increasing retinoid metabolism. However, excessive RA exposure is toxic for decidual cells and triggers a response that may lead to pregnancy failure.

Endometrial dysfunction caused by chronic endometritis: сlinical and morphological aspects

to determine the clinical and morphological aspects of endometrial dysfunction caused by chronic endometritis (CE). The study included 239 reproductive-aged patients: 93 were examined for abnormal uterine bleeding; 37 patients of them had a history of miscarriage and secondary infertility, 17 patients had primary infertility (Group 1). The remaining 105 patients with infertility were examined for future in vitro fertilization (Group 2). A comparison group consisted of 41 patients with normal menstrual cycles and reproductive function across the cycle, who had separate diagnostic curettage before forthcoming surgery for uterine myoma. All the women in Groups 1 and 2 underwent standard clinical and morphological investigations, histopathological examination of the material obtained during hysteroscopy with separate diagnostic curettage (Group 1), and aspiration biopsy (Group 2) with the sections being stained with hematoxylin and eosin and by Mallory's method. Immunohistochemical diagnosis was used to assess endometrial receptivity to steroid hormones and glycodelin. Antibodies against CD4, СD8, and CD20 were employed to study local immunity. In Group 1, 52 (55.9%) of the 93 patients admitted to hospital for abnormal uterine bleeding were found to have CE on the basis of a morphopathological examination of the material after separate diagnostic study. In Group 2, CE was established in 59 (56.9%) of the 105 patients after postmortem examination. The patients with CE had a history of reproductive significant infections, such as Chlamydia, Trichomonas, Ureaplasma Mycoplasma, cytomegalovirus, papillomavirus infections, genital herpes, genital candidiasis, and bacterial vaginosis. The CE groups showed functional disorders of the endometrial glandular and surface epithelium. In the middle stage of proliferation, the expression of glycodelin in the glandular epithelial cells was detected to be moderate to strong in 83.3%. During the periovulatory period, no secretion of glycodelin is of fundamental importance for the regulation of reproductive function because this protein has contraceptive activity, by blocking the binding of sperm to the zona pellucida. Accordingly, endometrial glycodelin production during the proliferative phase, which has been identified by the authors in patients with CE, may be one of the pathogenic mechanisms for the development of infertility. In addition, the patients in Groups 1 and 2 compared with those in the comparison group were noted to have a decrease in CD4 cell counts with a simultaneous increase in CD8 expression and a reduction in CD20 levels, especially in Group 2. The patients with SE were identified to have endometrial dysfunction characterized by lower reception to steroid hormones, impairment in glycodelin secretion, retardation in the development of pinopods and in the phase of the menstrual cycle, and local immunity disorders. The above endometrial changes should be taken into account in the pregravid preparation of patients with CE.

The physiological expression of scavenger receptor SR-B1 in canine endometrial and placental epithelial cells and its potential involvement in pathogenesis of pyometra

Pyometra, the purulent inflammation of the uterus, is a common uterine disease of bitches that has potentially life-threatening consequences. The opportunistic bacterial infection of the uterus often progresses into the serious systemic inflammatory response syndrome. In a previous study, we characterized epithelial foam cells in the canine endometrial surface occurring in metestrus, and we regularly observed pronounced epithelial foam-cell formations in pyometra-affected uteri. Therefore, it was assumed that the mechanism behind lipid droplet accumulation in surface epithelial cells might even increase bacterial binding capacity and promote pyometra development. Lipid droplet accumulation in epithelial cells is accomplished via specialized lipid receptors called scavenger receptors (SR). Scavenger receptor class B type 1 (SR-B1) is an important receptor for lipid accumulation in diverse cell types, but it is also a strong binding partner for bacteria, and thereby enhances bacterial adhesion and clinical signs of systemic inflammatory response syndrome. In the present study, after the isolation of metestrous surface epithelial cells from canine uteri by laser capture microdissection, SR-B1 was identified at the messenger RNA (mRNA) level by quantitative real time polymerase chain reaction and also at the protein level by means of immunohistochemistry. In pyometra-affected uteri, SR-B1 mRNA expression was higher than that in the healthy control samples, and SR-B1 protein was expressed in the surface and crypt epithelial cells. Furthermore, to understand the physiological role of SR-B1 expression in the metestrus surface epithelial cells, we investigated its expression in the epithelial cells of the glandular chambers of canine placenta in different stages of gestation because these cells are also characterized by lipid droplet accumulation. SR-B1 was present in the placental epithelial cells of the glandular chambers from 25 to 30 and 45 to 50 days of gestation, where basal and basal and/or apical expression patterns were observed. The physiological expression of SR-B1 in metestrous endometrial surface epithelia might be related to the implantation process and embryo development, as SR-B1 was also identified in the epithelial cells of the canine placental chambers. The increased levels of SR-B1 in pyometra-affected uteri indicate a potential role for this scavenger receptor in endometrial bacterial adhesion.

Quantitative morphological changes in the interplacentomal wall of the gravid uterine horn of cattle during pregnancy

BackgroundThe interplacentomal wall of the gravid uterine horn in cattle is the subject of reports dealing mainly with specific aspects of early pregnancy or the peripartal period. Only a very limited number of early and descriptive studies includes the whole period of pregnancy. Thus, there is a gap concerning quantitative morphological data of the uterine wall during pregnancy. We hypothesized that the specific requirements of pregnancy are reflected by significant and characteristic morphologic changes.MethodsInterplacentomal segments of the fetus-bearing horn of the uterus of 47 cows were collected at slaughter, assessed quantitatively by light microscopy, grouped into trimesters (trim), and data were analyzed statistically.ResultsDuring pregnancy there were significant increases (p<0.05) in the measured parameters: heights of the endometrial surface epithelium (31 increased to 46 and 46 μm, in the 1st, 2nd and 3rd trim, respectively), glandular epithelium (19.6 to 22.4 and 25.4 μm, respectively), diameters of glands (94 to 166 to 239 μm, respectively) and glandular lumina (56 to 122 to 188 μm, respectively). Volume density of the glandular epithelium did not change, while that of glandular lumina increased significantly (8 to 26 to 40% in the 1st, 2nd and 3rd trim, respectively) and of endometrial stroma decreased with ongoing pregnancy (67 to 46 to 37%; p<0.05).Diameters of myometrial smooth muscle cells (MSMC) (9.7 to 12.4 and 12.9 μm, respectively, for the 1st, 2nd and 3rd trim; p<0.05), and the volume fraction of myometrial stroma increased (6 to 10 to 13%; p<0.05), while decreases were observed in MSMC nuclear volume density (4.4 and 4.0 to 2.4%; p<0.05). The fraction of MSMC cytoplasm (89 to 85%) and the nucleus:cytoplasm ratio (0.05 to 0.03%) both decreased for the 1st vs. 3rd trim, respectively (p<0.05).ConclusionsThese results indicate that the interplacentomal wall of the gravid uterine horn is subjected to significant morphological changes during pregnancy, underlining the importance of endometrial surface epithelium and of gland hypertrophy for nourishment of the conceptus, of increased myometrial extracellular matrix for uterine tensile strength and of myometrial smooth muscle hypertrophy for expulsion of the fetus at term.

Changes in ovaries and uterus after aglepristone administration in the third week of luteal phase of non-pregnant bitches.

ObjectiveThe mechanism of aglepristone action in the placentation time in the bitch remains unclear. The aim of this study was to describe the mechanism by which aglepristone influences ovaries and uterus and to measure the levels of steroid sex hormones in non-pregnant bitches.Materials and MethodsFourteen bitches assigned to a study (n=9) and control (n=5) group were given aglepristone and saline solution, respectively, on the 19th and 20th day after LH peak. On the 26th day after LH peak an ovariohysterectomy was performed. Blood samples were screened for estradiol and progesterone concentrations. Ovaries and uterine horns and bodies were isolated for histological and morphometrical diagnosis and immunohistochemistry analysis of α-estrogen and progesterone receptor expression.ResultsA decrease of progesterone (p<0.01) and no differences in total estrogen level in the study group were observed. There were no significant differences either in the histomorphometry or α-estrogen and progesterone receptors expression in ovaries. Increase in expression of progesterone receptors in endometrium without surface epithelium of horns (p<0.05), endometrial surface epithelium (p<0.05), myometrium of uterine body (p<0.01) and estrogen receptors in endometrium without surface epithelium of horns (p<0.05) was observed. Elevated estrogen receptors probably increased sensitivity of tissues to estrogens in the bloodstream and led to notable inflammation, haemorrhages, and hyperplasia in endometrium with mononuclear immune cell infiltration. The myometrium of horns and endometrium of uterine body of study bitches were significantly thicker than in the control group (p<0.05 and p<0.01). Furthermore myometrium of uterine body was thicker than myometrium of horns (p<0.001) and expression of progesterone receptors was higher in uterine body (p<0.01). No differences were observed between endometrium of horns and body within groups.ConclusionTo the knowledge of the authors this is the first study, which describes the inflammatory effect developing in uterus in response to aglepristone administration, and attempts to elucidate its mechanisms.

The role of inherited thrombophilia and undifferentiated connective tissue dysplasia syndrome in the pathogenesis of female infertility: A clinical and morphological study

Impaired endometrial receptivity is a major cause of reproductive losses in in vitro fertilization (IVF) cycles given a normal embryo. Its causes may be associated with many diseases, including inherited thrombophilia (IT) and undifferentiated connective tissue dysplasia syndrome (uCTDS). However, endometrial receptivity remains little studied. to investigate the morphological and immunohistochemical substrates of impaired endometrial receptivity in women with uCTDS, IT, and their concurrence. Antibodies against ER, PgR, LIF, VEGF, and PAI-1 were used to morphologically and immunohistochemically examine pipelle endometrial biopsy specimens taken from 141 women in the implantation window (on days 6-7 after ovulation). In accordance with their clinical diagnoses, the patients were divided into 4 groups: 1) 13 patients with uCTDS; 2) 100 with IT; 3) 19 with uCTDS and IT; 4) 9 healthy surrogate mothers (a control group). In the examined groups, a total of 145 (90.1%) out of all the IVF protocols were unsuccessful. In the remaining 16 (9.9%) patients without exception, miscarriage started at less than 10 weeks' gestation. In the implantation window, the endometrium was immature in 101 (83.1%) women and corresponded to late proliferation or early secretion phases; 102 (84.3%) women were also found to have no mature pinopodes, pointing to the fact that the endometrial receptivity was very low. Immunohistochemical examination revealed the lower expression of the receptivity marker LIF in the endometrial surface epithelium and its higher expression in the stroma in the study groups (p < 0.05 for the uCTDS and uCTDS+IT groups) and the higher expression of PAI-1 and VEGF in the epithelium, stroma, and endothelium in the study groups than in the control group (p < 0.05), suggesting the intensity of neoangiogenetic processes and impaired fibrinolysis in these patients. uCTDS and IT are risk factors of impaired endometrial receptivity in the pathogenesis of infertility. The manifestations of impaired endometrial receptivity in this case are a decrease in mature pinopodes in the surface epithelium; focal stromal sclerosis; and redistribution of the receptivity marker LIF from the surface epithelium to the stroma, which may be used for diagnosis, prediction, and the development of targeted therapy.