Follicular Structures Research Articles

Pathohistological Findings after Bilateral Ovariectomy in Mares with Behavioral Problems

Behavioral problems in reproductively healthy mares are a challenging issue that is successfully treated with bilateral ovariectomy (BO). This laparoscopic procedure represents an alternative to conservative treatment for mares not intended for breeding and results in high owner satisfaction regarding behavioral improvement. However, a pathohistological explanation to justify surgical ovarian removal regarding animal welfare is lacking. Therefore, the objective of this study was to pathohistologically evaluate bilaterally removed, clinically unremarkable ovaries of mares with behavioral problems (bOE, n = 20) and to compare them with pathohistologically confirmed granulosa cell tumors of mares with neoplastic ovaries (GCT-uOE, n = 10). A complete data set including preliminary presentation, clinical examination, and serum anti-Müllerian hormone (AMH) and testosterone was further analyzed in both groups. Both hormones were significantly higher in GCT-uOE compared with bOE. Immunohistochemical expression of Ki-67, AMH, aromatase, epidermal growth factor receptor, calretinin, and epithelial cadherin in granulosa cells of large follicular structures in bOE did not differ from neoplastic granulosa cells in GCT-uOE. Ultrasonographically nondetectable early neoplastic changes were pathohistologically evaluated in 15% of mares and anovulatory-like follicles in 30% of mares in bOE and might be one explanation for the high success rate of BO in 85% of bOE in this study.

Follicular thyroid carcinoma in an inbred family of mongrel dogs in Trinidad & Tobago.

Thyroid tumors occur in many domestic species, but are most common in the dog, in which they are classified as follicular or medullary. During 2012-2016, we received tissue specimens or whole carcasses of 4 dogs with variable enlargement of the thyroid glands. The 2 males and 2 females were of mixed (mongrel) inbreeding, 3-4.5-y-old. All tumors had lobulated architecture forming follicular structures variably containing colloid. On immunohistochemistry of the tumors from 3 of the dogs, 2 were thyroglobulin positive, and all 3 were negative for calcitonin, confirming follicular thyroid carcinoma in 2 of the dogs. Thyroid carcinomas have not been reported previously in related mongrel dogs, to our knowledge.

Diagnostic utility of pharyngeal follicular structures in COVID-19: A large-scale cross-sectional study

ObjectivesPharyngeal follicles similar to those seen in influenza have been observed in patients with coronavirus disease 2019 (COVID-19), suggesting their potential as early-stage diagnostic markers. In this study, we examined the diagnostic potential of pharyngeal follicles for COVID-19, particularly the Omicron variant and its subtypes, to obtain basic data for AI-based diagnostic imaging tools. MethodsA cross-sectional study was conducted from July 21, 2022, to March 31, 2023, at the Tokyo Shinagawa Hospital's fever clinic. Participants aged ≥15 years who underwent real-time polymerase chain reaction testing for COVID-19 and pharyngeal examinations were included. Demographic details, symptom onset, throat pain, and vaccination status were also recorded. Pharyngeal structures were categorized into four groups: follicles, buds, mixed, or absent. ResultsOf the 1223 participants, 829 (67.8%) tested positive for COVID-19. Among those who tested positive, 73.6% (95% CI: 70.6%-76.6%) had follicular structures, compared to 52.8% (95% CI: 47.9%-57.7%) of those who tested negative (P = 1.0 × 10−12). Overall, 818 participants exhibited follicular structures (439 with follicles, 281 with buds, and 98 with mixed structures), while 405 lacked any follicular structures. Regression analysis identified throat pain and follicular structures as significant COVID-19 predictors (95% confidence intervals: 2.49-4.85 and 1.43-2.59, respectively). Mixed follicles were identified as a potentially characteristic feature of COVID-19. ConclusionPharyngeal follicular structures demonstrated high sensitivity for early COVID-19 diagnosis.

IgG4 glycosylation contributes to the pathogenesis of IgG4 Hashimoto's thyroiditis via the complement pathway.

To explore whether IgG4 is involved in the pathogenesis of IgG4 HT. Serum TgAb IgG4 and TPOAb IgG4 were measured in IgG4 HT and non-IgG4 HT. C1q, mannose-binding lectin (MBL), Bb, C3d, C4d and membrane attack complex (MAC) in thyroid tissues from IgG4 HT, non-IgG4 HT and controls were examined by immunohistochemistry. We assessed IgG4 and MAC deposition in mouse thyroid by immunohistochemistry after injecting purified IgG4 into mice. The glycosylation patterns of TgAb IgG4 from IgG4 HT were identified by MALDI-TOF-MS. The ability of IgG4 binding to MBL before and after deglycosylation was assessed by ELISA. MBL and MAC fluorescence were detected in thyrocytes after the addition of IgG4 or deglycosylated IgG4. Serum TgAb IgG4 and TPOAb IgG4 levels were higher in IgG4 HT. MBL, Bb, C3d, C4d and MAC levels were higher in thyroid tissues of IgG4 HT than in non-IgG4 HT (all P < 0.001). IgG4 colocalized with MBL by immunofluorescence. In mice, follicular cell structure disruption was observed after the injection of IgG4 from IgG4 HT, as well as the colocalization of IgG4 with MAC. High levels of TgAb IgG4 glycosylation patterns, including monogalactose glycan (G1F), galactose-deficient glycan (G0F), and high-mannose glycan (M5), were detected in IgG4 HT. After deglycosylation, IgG4 reduced its ability binding to MBL, and there was low MBL and MAC activation in thyrocytes. High levels of IgG4 glycosylation patterns, including G1F, G0F and M5, may activate the complement lectin pathway, thereby participating in the pathogenesis of IgG4 HT.

CD19-CAR T-cell therapy induces deep tissue depletion of B cells

ObjectivesCD19-targeting chimeric antigen receptor (CAR) T-cell therapy can induce long-term drug-free remission in patients with autoimmune diseases (AIDs). The efficacy of CD19-CAR T-cell therapy is presumably based on deep tissue...

Development of branchial ionocytes in embryonic and larval stages of cloudy catshark, Scyliorhinus torazame

In teleost fish, branchial ionocytes are important sites for osmoregulation and acid-base regulation by maintaining ionic balance in the body fluid. During the early developmental stages before the formation of the gills, teleost ionocytes are localized in the yolk-sac membrane and body skin. By comparing with teleost fish, much less is known about ionocytes in developing embryos of elasmobranch fish. The present study investigated the development of ionocytes in the embryo and larva of cloudy catshark, Scyliorhinus torazame. We first observed ionocyte distribution by immunohistochemical staining with anti-Na+/K+-ATPase (NKA) and anti-vacuolar-type H+-ATPase (V-ATPase) antibodies. The NKA- and V-ATPase-rich ionocytes appeared as single cells in the gill filaments from stage 31, the stage of pre-hatching, while the ionocytes on the body skin and yolk-sac membrane were also observed. From stage 32, in addition to single ionocytes on the gill filaments, some outstanding follicular structures of NKA-immunoreactive cells were developed to fill the inter-filament region of the gill septa. The follicular ionocytes possess NKA in the basolateral membrane and Na+/H+ exchanger 3 in the apical membrane, indicating that they are involved in acid-base regulation like single NKA-rich ionocytes. Three-dimensional analysis and whole-mount immunohistochemistry revealed that the distribution of follicular ionocytes was limited to the rostral side of gill septum. The rostral sides of gill septum might be exposed to faster water flow than caudal side because the gills of sharks gently curved backward. This dissymmetric distribution of follicular ionocytes is considered to facilitate efficient body-fluid homeostasis of catshark embryo.

Columnar Cell Thyroid Carcinoma: A Heterogeneous Entity Demonstrating Overlap Between Papillary Thyroid Carcinoma and Follicular Neoplasms.

Columnar cell papillary thyroid carcinoma (CC-PTC) is a morphologic subtype of papillary thyroid carcinoma with a variable prognosis. It is characterized by neoplastic thyroid follicular-derived cells with pseudostratified columnar morphology arranged in papillary or follicular structures with supranuclear or subnuclear vacuoles. The molecular profile of this subtype has only recently come under scrutiny, with mixed results. The aim of this study is to further explore the morphologic, immunohistochemical, and genetic profile of CC-PTC, as well as to correlate these features with clinical outcomes. CC-PTC cases were identified from 3 institutions. Immunohistochemistry (ER, CDX2) and molecular testing (DNA and RNA sequencing) were performed. Clinicopathologic parameters and patient outcomes were recorded. Twelve cases (2006-2023) were identified, all in adults (age 45-91). Two presented with disease outside the thyroid gland (neck and mediastinum) and two presented with distant metastasis. Four were high-grade differentiated thyroid carcinomas (necrosis or mitoses), one of which died of disease. Four were noninvasive or minimally invasive, one of which locally recurred. Three patients had lymph node metastases. ER and CDX2 were positive in 73% and 50%, respectively. Pathogenic mutations were found in TERT promoter (n = 3), RAS (n = 2), ATM, NOTCH1, APC, and ESR1, along with cases bearing AGK::BRAF fusion (n = 1), BRAF VE1 expression (n = 1), and NF2 loss (n = 1). This study represents the largest molecularly defined cohort of non-oncocytic thyroid carcinomas with columnar cell morphology. These tumors represent a genetically and behaviorally heterogeneous group of neoplasms, some of which have RAS-like or follicular neoplasm-like genetics, some of which have BRAF-p.V600E-like or classic papillary thyroid carcinoma-like genetics, and some of which remain unclear. Noninvasive or minimally invasive tumors showed an indolent course compared to those with angioinvasion, gross extrathyroidal growth, or high-grade morphology. Consideration could be given to reclassification of this neoplasm outside of the subtyping of papillary thyroid carcinoma in light of its genetic diversity, distinct morphology, and clinical behavior more closely aligned with follicular thyroid neoplasms.

Premature endocycling of Drosophila follicle cells causes pleiotropic defects in oogenesis.

Endocycling cells grow and repeatedly duplicate their genome without dividing. Cells switch from mitotic cycles to endocycles in response to developmental signals during the growth of specific tissues in a wide range of organisms. The purpose of switching to endocycles, however, remains unclear in many tissues. Additionally, cells can switch to endocycles in response to conditional signals, which can have beneficial or pathological effects on tissues. However, the impact of these unscheduled endocycles on development is underexplored. Here, we use Drosophila ovarian somatic follicle cells as a model to examine the impact of unscheduled endocycles on tissue growth and function. Follicle cells normally switch to endocycles at mid-oogenesis. Inducing follicle cells to prematurely switch to endocycles resulted in the lethality of the resulting embryos. Analysis of ovaries with premature follicle cell endocycles revealed aberrant follicular epithelial structure and pleiotropic defects in oocyte growth, developmental gene amplification, and the migration of a special set of follicle cells known as border cells. Overall, these findings reveal how unscheduled endocycles can disrupt tissue growth and function to cause aberrant development.

In Vitro Growth of Human Follicles: Current and Future Perspectives.

Ovarian tissue cryopreservation is gaining importance as a successful method to restore fertility to girls and young women at high risk of sterility. However, there are concerns regarding the safety of transplantation after ovarian tissue cryopreservation due to the high risk of reintroducing cancer cells and causing disease recurrence. In these cases, the development of culture systems that support oocyte development from the primordial follicle stage is required. Notable achievements have been reached in human follicle in vitro growth in the past decade. Currently, systems for the in vitro culture of ovarian tissue are based on two-dimensional substrates that do not support the survival of follicles or recapitulate the mechanical heterogenicity in the mammalian ovary. Recognition of the importance of special arrangements between cells has spurred research in three-dimensional culture systems, and the provision of a precise culture system that maximizes the diffusion of nutrients and gases through the follicles has raised interest in advanced biomimetic models. The current review critically examines various culture systems employed for the in vitro development of follicles, with a particular focus on solutions utilizing Organ-on-a-Chip (OOC) technology. The emphasis on OOC technology underscores its role as a promising avenue in ensuring the successful cultivation and maintenance of follicular structures during the culture period.

Cystic folliculosebaceous hamartoma: an unusual histopathological entity: a case report

The skin covers our body and exhibits a complex structure that is adapted to the different body areas. The scalp skin is distinctive, and the histopathological alterations in its diseases also present distinctive features. We present the clinical case of a 28 year old female patient, with no significant medical history. She reported a nodular tumor on the left parietal region of the scalp, which had been present for 10 years and showed slow growth. The patient had no major discomfort other than an occasional discharge of scant whitish material upon applying pressure. Intralesional corticosteroids were administered but had no effect. Over the following year, the discomfort increased, leading to the decision to remove it. The anatomopathological study found dilated follicular hairy structures in the dermis filled with keratin and debris, surrounded by multiple sebaceous glands that flow there, all surrounded by a characteristic mesenchymal cells population, diagnosing a folliculosebaceous cystic hamartoma.

Microstructural analysis of meat and internal organs of broiler chickens using a probiotic biological product

Probiotic preparation containing bacteria of the genus Bacillus subtilis and Bacillus licheniformis used for feeding broiler chickens to improve feed digestion, nutrient absorption, increase immune status and productivity, and for the prevention and treatment of various poultry diseases. The purpose of the study is to conduct histological tests of broiler chicken slaughter products when they were administered a probiotic biologic medical product in doses of: 0.5 g, 2.0, and 4.0 g per 10 dm3 of water. The material was examined by the histological method. It was found that the muscle fibres in the pectoralis major are of the same type, evenly directed, the cytoplasm of muscle fibres is moderately eosinophilic, uniformly light pink, and minor layers of adipose tissue are found between the bundles of muscle fibres. The morphological architectonics of the heart muscle are preserved, cardiomyocytes are homogeneous and have a clear orientation. The microstructure of the liver of broiler chickens is unchanged: hepatocytes are collected in the same type of groups; the central veins are desolate; the cytoplasm of these cells is homogeneous, clear, and pink; the nuclei are weakly basophilic. In the spleen, the follicular structure is formed, leukocytes are diffusely placed at different stages of differentiation; vessels in significant numbers, thickened, of different calibre. The cuticle of the muscular part of the stomach contains the epithelial layer, the volume part of the connective tissue base layer is revealed; muscle fibres are located under the mesenchymal base of the cuticle. Lungs by morphological structure have bronchial tubes throughout the structure, which contain blood cells. According to the results of the conducted studies, a beneficial effect of a probiotic biological product at a dose of 4.0 g/10 dm3 of water on the morphology of the pectoralis major and internal organs of broiler chickens was established. Therefore, a probiotic at a dose of 4.0 g/10 dm3 of water during the drinking of broiler chickens can be recommended to increase productivity and produce safe slaughter products. The practical significance of the results obtained is to determine the features of the effect of feeding poultry with different doses of probiotics on the microstructure of its slaughter products, which is important for obtaining the best effect from its use

Studies on clinicopathological features of duodenal-type follicular lymphoma of 18 patients

To investigate the clinical and pathological characteristics of duodenal-type follicular lymphoma (D-FL), and to deepen the understanding of Duodenal-type follicular lymphoma. The clinical symptoms, endoscopic features, pathologic features, immunophenotype, molecular pathological features and treatment follow-up of 18 D-FL patients diagnosed in Department of Pathology, Beijing Tiantan Hospital affiliated to Capital Medical University between January 2020 and July 2023 were summarized. A total of 18 patients with D-FL were included, including 10 males and 8 females. The median age was 49 (32-69) years respectively. Most of the patients were found during gastroenteroscopy or presented with the common gastrointestinal symptoms of stomach pain, acid reflux, vomiting and diarrhea. Most endoscopic findings were multiple small gray and white polyposis. In the pathological morphology, the mucous layer and submucous layer showed lymphoid follicular structures with full and strained follicles. The immunophenotype showed that the tumor cells strongly expressed CD20 and BCL2 and had low proliferation activity. Immunoglobulin clonal analysis of 1 case showed IgK monoclonal rearrangement (1/1). FISH showed 1 case of BCL2 gene rearrangement (1/3). All patients did not receive targeted chemotherapy and adopted a wait-and-see strategy. Median follow-up was 12 (2-34) months. This study shows that D-FL is an indolent lymphoma, which tends to occur in the duodenum and has a good prognosis.

Single-cell sequencing reveals the heterogeneity of B cells and tertiary lymphoid structures in muscle-invasive bladder cancer

BackgroundMuscle-invasive bladder cancer (MIBC) is a highly aggressive disease with a poor prognosis. B cells are crucial factors in tumor suppression, and tertiary lymphoid structures (TLSs) facilitate immune cell recruitment to the tumor microenvironment (TME). However, the function and mechanisms of tumor-infiltrating B cells and TLSs in MIBC need to be explored further.MethodsWe performed single-cell RNA sequencing analysis of 11,612 B cells and 55,392 T cells from 12 bladder cancer patients and found naïve B cells, proliferating B cells, plasma cells, interferon-stimulated B cells and germinal center-associated B cells, and described the phenotype, gene enrichment, cell–cell communication, biological processes. We utilized immunohistochemistry (IHC) and immunofluorescence (IF) to describe TLSs morphology in MIBC.ResultsThe interferon-stimulated B-cell subtype (B-ISG15) and germinal center-associated B-cell subtypes (B-LMO2, B-STMN1) were significantly enriched in MIBC. TLSs in MIBC exhibited a distinct follicular structure characterized by a central region of B cells resembling a germinal center surrounded by T cells. CellChat analysis showed that CXCL13 + T cells play a pivotal role in recruiting CXCR5 + B cells. Cell migration experiments demonstrated the chemoattraction of CXCL13 toward CXCR5 + B cells. Importantly, the infiltration of the interferon-stimulated B-cell subtype and the presence of TLSs correlated with a more favorable prognosis in MIBC.ConclusionsThe study revealed the heterogeneity of B-cell subtypes in MIBC and suggests a pivotal role of TLSs in MIBC outcomes. Our study provides novel insights that contribute to the precision treatment of MIBC.

MORPHOLOGICAL MECHANISMS OF RADIATION-INDUCED ADRENAL ADAPTATIONS AND THE LEVEL OF RADIONUCLIDE CONTENT IN THE WHITE-CHESTED HEDGEHOG IN A ZONE OF HIGH RADIOACTIVE CONTAMINATION

For the first time, anatomical, histological and morphometric criteria for radiation-induced damage to the thyroid gland of the river otter have been determined. The lobes of the thyroid gland do not undergo morphological changes,and they have a permanent elongated ribbon-like shape. The height of the follicular epithelium and the Brown index are among the signs that reflect the functional state of the thyroid gland. In old animals, the Brown index has the highest value - 19.49 ± 0.39 conventional units. Structural and adaptive changes indicate that the thyroid glands of the river otter in the radiation zone of habitat belong to the glands of the small follicular type of structure. With age, a few large follicles are found, and in the early gerontological period, also zones of disorganization of parenchymal structures with complete disappearance of the follicular structure of the gland or desquamation of the thyroid epithelium. In sexually mature animals, the specific activity of 137Cs in the thyroid gland is 0.78±0.17 kBq/kg.

Localization of DC-SIGN Expressing Cells in Follicular Lymphoma

The high incidence of unusual mannose-rich glycans on the expressed surface immunoglobulins of follicular lymphoma (FL) suggests a pathogenic role for this modification. While lectin-mediated signaling has been proposed to provide trophic support to FL cells, the localization of the lectins has not been extensively characterized. Dendritic Cell-Specific Intercellular adhesion molecule-3-Grabbing Non-integrin (DC-SIGN) is a mannose-selective lectin named for its expression on classic marrow-derived dendritic cells. In vitro, recombinant DC-SIGN induces signaling in primary FL cells. The nodules of Follicular lymphoma (nFL) are the neoplastic counterparts of normal germinal centers (GC). Both GC and nFL contain variable numbers of centrocytic and/or centroblastic B cells, T-cells, and follicular dendritic cells (FDCs), but macrophages are typically found only in GC. Although termed “follicular dendritic cells”, FDCs are thought to be derived from non-blood stem-cells, potentially pericytes. Therefore, nFL lack classic dendritic cells and macrophages so it is unclear what cells in FL could express DC-SIGN. Therefore, we systematically characterized FDC and DC- SIGN localization in sixteen FL and nine Follicular hyperplasia (FH) lymph nodes. Using flow cytometry of disaggregated FL nodes, we were not able to identify a specific cell population expressing DC-SIGN. However, using immunohistochemistry and Immunofluorescence methods, we identified nine cases of FH and five cases of FL (n=5/16) with DC-SIGN and FDC co-localization. Immunohistochemical stains of the FDCs using CD23 and CD21 showed that the follicular dendritic structures were disrupted in almost all the FL cases assessed showing either a peripheral crescentic staining or broken FDC meshwork within the follicle. We identified five cases of FL with an average of more than four well visualized and complete FDC structures staining per low power field (4X) while the remaining cases had an average of less than two complete FDC network staining. There was near complete absence of CD21 positive FDCs meshwork identified in 50% of the FL cases compared to only one case lacking CD23 positive FDCs structure staining. In contrast, FH cases (n=9) showed complete staining of the FDC meshwork within the follicles with both CD21/CD23. For FH, the average number of complete FDC staining with CD23 was 18 while an average of 10 complete FDC meshworks stained with CD21. Furthermore, immunofluorescence imaging analysis showed different pattern of localization of CD23 positive FDC with DC-SIGN with between the two conditions. In FH, DC-SIGN and CD23 colocalization was identified mainly in the light zone. For FL, we observed that DC-SIGN overlap with CD23 localized in the intra-follicular areas and co-localized with CD163 (M2 macrophages) in the inter-follicular zones. Confocal imaging confirmed colocalization of CD23 and DC-SIGN on FDCs with close association to MUM1-positive B cells in both GC and nFL. Additional analysis also showed that 80% (n=5) of the cases which had more than four complete FDC structures staining with CD23 co-localized with DC-SIGN in the intra-follicular areas and the cases with complete FDC network disruption did not. There was no significant relationship identified between the extent of FDC networks and the fraction of non-neoplastic B cells in the FL cases. In summary, our data show that DC-SIGN is expressed on FDCs in FL and FH even though FDCs are not the marrow-derived DCs for which DC-SIGN is named. Furthermore, localization of DC-SIGN to the follicle suggests a potential role for the microenvironment in the pathogenesis of FL and possible therapeutic target.

Progressively transformed germinal center-like follicular T-cell lymphoma:a clinicopathological analysis of 14 cases

Objective: To investigate the clinicopathologic features of progressively transformed germinal center-like follicular T-cell lymphoma (PTGC-like FTCL). Methods: The clinicopathologic data of 14 PTGC-like FTCL cases that were diagnosed at the Beijing Friendship Hospital Affiliated to the Capital Medical University from January 2017 to January 2022 were retrospectively collected. Clinicopathological features, immunophenotype, and Epstein-Barr virus (EBV) infection status were analyzed in these cases. Polymerase chain reaction (PCR) was performed to detect the clonal gene rearrangements of T cell receptor (TCR) and the immunoglobulin (Ig) in 10 and 8 cases, respectively. Results: The male to female ratio was 5∶2. The median age was 61 years (range 32-70 years). All patients had lymphadenopathy at the time of diagnosis. By using the Ann Arbor system staging, seven cases were classified as stage Ⅰ-Ⅱ, and seven cases as stage Ⅲ-Ⅳ. Seven cases had B symptoms, four cases had splenomegaly, and two cases had skin rash and pruritus. Previously, three cases were diagnosed as classic Hodgkin's lymphoma, three cases as small B-cell lymphoma, two cases as atypical lymphoid hyperplasia unable to exclude angioimmunoblastic T-cell lymphoma (AITL), one case as EBV-associated lymphoproliferative disorder, and one case as peripheral T-cell lymphoma (PTCL) associated with the proliferation of B cells. All the 14 cases showed that the large nodules were composed of mature CD20+, IgD+B lymphocytes admixed with small aggregates of neoplastic cells with pale to clear cytoplasm. Moreover, hyperplastic germinal centers (GCs) and Hodgkin/Reed-Sternberg-like (HRS-like) cells were seen within these nodules in two and five cases, respectively. The neoplastic cells expressed CD3 (14/14), CD4 (14/14), PD1 (14/14), ICOS (14/14), CD10 (9/14), bcl-6 (12/14), CXCL13 (10/14), and CD30 (10/14). The HRS-like cells in five cases expressed CD20 (2/5), PAX5 (5/5), CD30 (5/5), CD15 (2/5), LCA (0/5), OCT2 (5/5) and BOB1 (2/5). Moreover, neoplastic T cells formed rosettes around HRS-like cells. EBV-encoded RNA (EBER) in situ hybridization showed scattered, small, positive bystander B lymphocytes in 8/14 cases, including 3/5 cases containing HRS-like cells. All tested cases (including five with HRS-like cells) showed monoclonal TCR gene rearrangement and polyclonal Ig gene rearrangement. Conclusions: PTGC-like FTCL is a rare tumor originated from T-follicular helper cells. It could be distinguished from angioimmunoblastic T-cell lymphoma by the formation of follicular structure, and lack of follicular dendritic cell proliferation outside the follicles and the polymorphous inflammatory background. In addition, it should be differentiated from lymphocyte-rich classical Hodgkin's lymphoma and low-grade B cell lymphoma.

Luteinizing hormone stimulates ingression of mural granulosa cells within the mouse preovulatory follicle†.

Luteinizing hormone (LH) induces ovulation by acting on its receptors in the mural granulosa cells that surround a mammalian oocyte in an ovarian follicle. However, much remains unknown about how activation of the LH receptor modifies the structure of the follicle such that the oocyte is released and the follicle remnants are transformed into the corpus luteum. The present study shows that the preovulatory surge of LH stimulates LH receptor-expressing granulosa cells, initially located almost entirely in the outer layers of the mural granulosa, to rapidly extend inwards, intercalating between other cells. The cellular ingression begins within 30 min of the peak of the LH surge, and the proportion of LH receptor-expressing cell bodies in the inner half of the mural granulosa layer increases until the time of ovulation, which occurs at about 10h after the LH peak. During this time, many of the initially flask-shaped cells appear to detach from the basal lamina, acquiring a rounder shape with multiple filipodia. Starting at about 4h after the LH peak, the mural granulosa layer at the apical surface of the follicle where ovulation will occur begins to thin, and the basolateral surface develops invaginations and constrictions. Our findings raise the question of whether LH stimulation of granulosa cell ingression may contribute to these changes in the follicular structure that enable ovulation.

Loss of ARHGAP40 expression in basal cell carcinoma via CpG island hypermethylation.

Basal cell carcinoma (BCC) is the most common malignant tumour arising from the basal cells of the epidermis or follicular structures. The aetiology of BCC is a multifactorial combination of genotype, phenotype and environmental factors. The pathogenesis of BCC remains unclear, with diverse and complex signalling pathways involved. ARHGAP40 is a Rho GTPase-activating protein (RhoGAP). Rho GTPases play a crucial role in the formation and progression of numerous cancers. The expression levels and roles of ARHGAP40 in BCC have not been explored. Here, ARHGAP40 expression was detected in a set of formalin-fixed, paraffin-embedded (FFPE) samples of basal cell carcinoma, paracancerous normal skin and benign skin lesions. The epigenetic mechanism that downregulates ARHGAP40 in basal cell carcinoma was investigated. We found that ARHGAP40 is expressed in normal basal cells and most benign skin lesions but lost in most basal cell carcinomas. We detected CpG island hypermethylation at the promoter-associated region of ARHGAP40. Our data suggest that ARHGAP40 is downregulated in BCC due to hypermethylation. ARHGAP40 protein is a potential novel biomarker for distinguishing trichoblastoma from BCC. This report is preliminary, and extensive research into the role of ARHGAP40 in BCC carcinogenesis and its potential as a treatment target is required in the future.

PGE2 functions in ovoviviparous teleost black rockfish (Sebastes schlegelii): evolutionary status between parturition and ovulation†.

Fish have evolved various reproductive strategies including oviparity, viviparity, and ovoviviparity, which undoubtedly affect the survival of the whole species continuity. As the final step in reproduction, parturition in viviparous vertebrate and ovulation in oviparous teleost seem to share a similar mechanism, when prostaglandins (PGs) act as the trigger to launch the whole process. In the present study, ovoviviparous teleost black rockfish (Sebastes schlegelii) is employed as the research object. Intraperitoneal injection showed that PGE2 (500μg/kg) could activate the delivery reactions in perinatal black rockfish. RNA-seq data of ovary in perinatal period revealed transcriptional change in cell junction, inflammation, and apoptosis, which is related to mammal parturition and teleost ovulation. Further results proved the positive correlation between ptger EP2 and previous mentioned pathways. Subsequent experiment proved that PGE2 was able to induce the ovulation and spawning in unfertilized individuals, which had a bilayer follicular structure compared to monolayer follicular in perinatal period black rockfish. Both unfertilized and perinatal ovary matrix could response to PGE2 stimulation. In conclusion, the function of PGE2 in activating both parturition and ovulation in a relatively different pathways conserved with viviparity or oviparity provided novel evidence of the evolutionary status of ovoviviparous vertebrates.

FRI390 The Effects Of Chronic Asprosin Administration On Ovarian Tissue

Abstract Disclosure: H. Kelestimur: None. Z. Oz: None. M. Ozdede: None. I. Serhatlioglu: None. N. Kaya Tektemur: None. E. Kacar: None. Purpose: Asprosin is a novel glucogenic and orexigenic hormone produced by the fibrillin 1 (FBN1) gene that is secreted by white adipose tissue during fasting. Fibrillins (FBNs) are structural and signalling proteins found mainly in the ovarian stroma, tunica albuginea and theca layers. The aim of this study was to determine the effects of asprosin on ovarian tissue in the female rats. Materials and methods: Twenty-four female Sprague-Dawley rats were randomly divided into 2 groups (n=12) as control and asprosin. Asprosin and control groups were given intraperitoneal saline at doses of 500 ng/kg and 1 ml/kg, respectively, at 14.00 every day for eight weeks. After the application, decapitation was performed, and the rapidly removed ovarian tissues were placed in a 10% formaldehyde solution for fixation. Formalin-fixed ovaries were dehydrated in a graded alcohol series and graded ethanol, respectively After that, all tissues were embedded in paraffin wax. The ovaries were cut into 5-µm sections and stained with hematoxylin and eosin (H&amp;E) and also Masson trichrome staining. Ovarian follicular reserve and fibrosis were evaluated by light microscopy. The follicles were histologically classified as primordial, primary, secondary, and Graaf and all follicular structures were counted in each section. The fibrosis was evaluated with Masson’s trichrome staining and scored from 0 to 3 semi-quantitatively (0 = no fibrosis, 1 = low fibrosis, 2 = intermediate fibrosis, 3 = severe fibrosis). Results: In the asprosin group, unlike the control group, occasional congestion was observed in the vessels located in the ovarian medulla. Apart from this, no histopathological changes were found. An increase in fibrosis was detected in the ovarian sections of the asprosin group when compared to the control group (p = 0,035). In the light microscopic evaluation of the ovarian sections of the rats in the asprosin group, the primary and secondary follicle numbers were significantly higher than those in the control group (p = 0,008 and p = 0,047 respectively). However, the difference between the control and asprosin groups in terms of the primordial follicle, Graafian follicle and corpus luteum numbers were not statistically significant. Conclusion: Our results have shown that chronic asprosin administration causes an increase in the number of primary and secondary follicles, suggesting that changes in ovarian steroidogenesis and folliculogenesis depending on the application may lead to positive effects on female fertility. Keywords: Asprosin, adipokine, ovarian follicle. Acknowledgement: This study was supported by TUBITAK (Project: 220S744). Presentation: Friday, June 16, 2023