Low doses of alkylating agents do not harm human ovarian tissue destined for cryopreservation.

Objective: To investigate the impact of non-gonadotoxic doses of alkylating agents on human ovarian cortex.

Design: Retrospective study.

Setting: Academic research center.

Endometrial stromal cell signaling and microRNA exosome content in women with adenomyosis.

Adenomyosis is a chronic, estrogen-driven disorder characterized by the presence of endometrial glands and stroma within the myometrium. Despite its significant impact on reproductive health and quality of life, the pathogenesis of the disease remains unclear. Both the glandular and stromal compartments of eutopic endometrium from women with adenomyosis show alterations compared to healthy subjects.

Expression of Endometrial Receptivity Markers throughout the Menstrual Cycle in Women with and without Uterine Adenomyosis.

: While it is known that adenomyosis is associated with poor reproductive outcomes, the underlying mechanisms are unclear, and to date, there is no standard treatment protocol for these patients. Endometrium from adenomyosis patients is characterized by several abnormalities, potentially resulting in impaired receptivity and subsequent implantation failure. : Endometrial biopsies were collected from 26 women with adenomyosis and 26 control subjects.

Generation of epithelial-stromal assembloids as an advanced in vitro model of impaired adenomyosis-related endometrial receptivity.

Objective: To create a novel, more advanced in vitro model of human endometrium, using so-called assembloids, looking to explore endometrial receptivity in adenomyosis.

Design: Evaluation of assembloid responsiveness to hormonal stimulation by immunohistochemistry, enzyme-linked immunosorbent assay, and scanning electron microscopy.

Setting: University-based research unit in gynecology.

Assessing the effect of adipose-tissue-derived stem cell conditioned medium on follicles and stromal cells in bovine ovarian tissue culture.

Research Question: Does adipose-tissue-derived stem cell conditioned medium (ASC-CM) supplementation enhance follicle and stromal cell outcomes in vitro?

Design: Bovine ovaries (n = 8) were sectioned and cultured in vitro for 8 days in two different groups: (i) standard culture (OT Ctrl D8); and (ii) culture with ASC-CM supplementation (OT + CM D8). Half of the culture medium was replaced every other day, and stored to measure the production of oestradiol. Follicle classification was established using haematoxylin and eosin staining.

Evaluating testicular tissue for future autotransplantation: focus on cancer cell contamination and presence of spermatogonia in tissue cryobanked for boys diagnosed with a hematological malignancy.

Study Question: What is the contamination rate by cancer cells and spermatogonia numbers in immature testicular tissue (ITT) harvested before the start of gonadotoxic therapy in boys with a hematological malignancy?

Summary Answer: Among our cohort of boys diagnosed with acute lymphoblastic leukemia (ALL) and lymphomas, 39% (n = 11/28) had cancer cells identified in their tissues at the time of diagnosis and all patients appeared to have reduced spermatogonia numbers compared to healthy reference cohorts.

What Is Known Already: Young boys affected by a hematological cancer are at risk of contamination of their testes by cancer cells but histological examination is unable to detect the presence of only a few cancer cells, which would preclude autotransplantation of cryobanked ITT for fertility restoration, and more sensitive detection techniques are thus required. Reduced numbers of spermatogonia in ITT in hematological cancer patients have been suggested based on results in a limited number of patients.

Influence of ovarian stromal cells on human ovarian follicle growth in a 3D environment.

Study Question: Do ovarian stromal cells (OSCs) influence the viability and growth of human preantral follicles ?

Summary Answer: A feeder layer of OSCs promotes the growth and transition of low developmental stage follicles to the primary/secondary stage while maintaining a high proportion of viable follicles.

What Is Known Already: In the ovary, follicles rely on the support of ovarian cells, which secrete essential factors for their survival and development. This phenomenon has also been demonstrated through the 3D culture of isolated mouse primary and secondary follicles on a feeder layer of OSCs.

Intravascular large cell B lymphoma presenting as central nervous system pseudo-vasculitis: A rare diagnostic challenge.

Intravascular large B cell lymphoma (IVLBCL) is a very rare subtype of aggressive non-Hodgkin B cell lymphoma characterized by intravascular proliferation of clonal B lymphocytes, classically associated with pulmonary and cutaneous disease and, less frequently, with central nervous system (CNS) involvement. Brain imaging findings are usually non-specific, with evidence of multiple vascular occlusions and stroke as non-specific multifocal abnormalities. We present an exceptionally rare case of IVLBCL in a patient with unexplained inflammatory syndrome with B symptoms and rapidly progressive neurological impairment, with multifocal hemorrhagic and tumefactive brain lesions seen on MRI.

[Unusual gluteal localization of unicentric Castleman's disease: A case report and review of the literature].

Background: Castleman's disease is a rare and benign lymphoproliferative disorder which can be unicentric (UCD) or multicentric (MCD). UCD usually involves a single lymph node or less frequently a group of lymph nodes. The most common sites of nodal UCD presentation are the mediastinum, neck, abdomen and retroperitoneum.

Are lower levels of apoptosis and autophagy behind adenomyotic lesion survival?

Research Question: How are markers of cell death, invasiveness and progesterone signalling expressed in endometrium and ectopic lesions from adenomyosis patients?

Design: Formalin-fixed paraffin-embedded tissue was collected from 15 control and 15 adenomyosis participants . To assess cell survival capacity, caspase 3 and microtubule-associated proteins 1A/1B light chain 3B (LC3B) were immunolabelled as markers of apoptosis and autophagy respectively. Matrix metalloproteinase 9 (MMP9) expression served as a marker of extracellular matrix degradation and invasion activity.

Assessment of folliculogenesis in ovarian tissue from young patients with Turner syndrome using a murine xenograft model.

Objective: To study the impact of aneuploid granulosa and stromal cells on folliculogenesis of small ovarian follicles from patients with mosaic Turner syndrome (TS) using a murine xenograft model.

Design: Laboratory study.

Setting: University hospital.

purging of cancer cells from ovarian tissue using photodynamic therapy: a novel strategy to restore fertility in leukemia patients.

Study Question: Is it possible to purge leukemia cells from ovarian tissue (OT) fragments before transplantation?

Summary Answer: Our photodynamic therapy (PDT) approach has been shown to efficiently destroy leukemia cells from tumor-infiltration mimicking models (TIMs), indicating the feasibility of this technique to purge OT samples.

What Is Known Already: Autotransplantation of cryopreserved OT is the most suitable option to preserve fertility for prepubertal girls and women who require immediate cancer treatment. Up until now, more than 200 live births have already been reported after OT cryopreservation and transplantation.

Follicle outcomes in human ovarian tissue: effect of freezing, culture, and grafting.

Objective: To study the effect of freezing, in vitro culture (IVC) and grafting to chorioallantoic membrane (CAM) on follicle outcomes in human ovarian tissue.

Design: An experimental study.

Setting: University-based research laboratory.

Photodynamic therapy using OR141-loaded nanovesicles for eradication of leukemic cells from ovarian tissue.

In 2020, the estimated number of new leukemia cases was higher than 30,000 in girls between 0 and 19 years old. Due to cancer treatment, some of these patients may lose both endocrine and reproductive functions. Transplantation of cryopreserved ovarian tissue is not advised after cancer remission because it has a high risk of reintroducing malignant cells in the patient, potentially leading to leukemia recurrence.

miR-199a Downregulation as a Driver of the NOX4/HIF-1α/VEGF-A Pathway in Thyroid and Orbital Adipose Tissues from Graves' Patients.

Graves' disease (GD) is an autoimmune thyroiditis often associated with Graves' orbitopathy (GO). GD thyroid and GO orbital fat share high oxidative stress (OS) and hypervascularization. We investigated the metabolic pathways leading to OS and angiogenesis, aiming to further decipher the link between local and systemic GD manifestations.

Ectopic Endometrium: The Pathologist's Perspective.

Endometriosis and adenomyosis are two frequent diseases closely linked, characterized by ectopic endometrium. Despite their benign nature, endometriosis and adenomyosis impair women's quality of life by causing pain and infertility and an increase in the incidence of gynecological malignancies has been reported. Since the first description of ectopic endometrium in 1860, different attempts have been made to describe, classify and understand the origin of these diseases.

Identifying Common Pathogenic Features in Deep Endometriotic Nodules and Uterine Adenomyosis.

Increasing imaging data point to a link between deep endometriotic nodules (DENs) and uterine adenomyosis (AD). The study aimed to investigate this link at the histological level and detect potential features shared by the two diseases. We collected formalin-fixed paraffin-embedded tissue (endometrium and lesions) from women with DENs of the rectovaginal septum ( = 13), AD ( = 14), and control subjects ( = 14).

Mitochondrial content, activity, and morphology in prepubertal and adult human ovaries.

Purpose: To investigate whether mitochondrial content, activity, and morphology differ in prepubertal versus adult ovarian follicles.

Methods: Ovarian tissue was collected from 7 prepubertal girls (age 1-10 years) and 6 adult women (age 20-35 years). Primordial and primary follicles were isolated from frozen-thawed prepubertal and adult ovarian tissue and their viability was assessed.

Basal lamina characterization in frozen-thawed and long-term grafted human prepubertal ovarian tissue.

Research Question: Are there differences in the composition and structure of the basal lamina surrounding follicles in prepubertal versus adult human ovarian tissue?

Design: Frozen-thawed human ovarian tissue from six prepubertal and seven adult patients was divided into three fragments in each case: two for non-grafted tissue evaluation and one for long-term xenografting to mice. Collagen IV and laminin expression were investigated by immunohistochemistry before and after grafting. The basal lamina was analysed by transmission electron microscopy on frozen-thawed tissue.

New insights into the GDF9-Hedgehog-GLI signaling pathway in human ovaries: from fetus to postmenopause.

Research Question: Are glioma-associated oncogene homolog 1, 2, and 3 (GLI1, 2, and 3) and protein patched homolog 1 (PTCH1) specific markers for precursor theca cells in human ovaries as in mouse ovaries?

Design: To study the GDF9-HH-GLI pathway and assess whether GLI1 and 3 and PTCH1 are specific markers for precursor theca cells in the human ovary, growth differentiation factor 9 (GDF9), Indian Hedgehog (IHH), Desert Hedgehog (DHH), Sonic Hedgehog (SHH), PTCH1 and GLI1, 2 and 3 were investigated in fetal (n=9), prepubertal (n=9), reproductive-age (n=15), and postmenopausal (n=8) human ovarian tissue. Immunohistochemistry against GDF9, IHH, DHH, SHH, PTCH1, GLI1, GLI2, and GLI3 was performed on human ovarian tissue sections fixed in 4% formaldehyde and embedded in paraffin. Western blotting was carried out on extracted proteins from the same samples used in the previous step to prove the antibodies' specificity.

Investigation of the role of platelets in the aetiopathogenesis of adenomyosis.

Research Question: Do platelets aggregate in adenomyotic lesions and participate in adenomyosis pathogenesis and related fibrosis?

Design: Eutopic and ectopic endometrium from 17 patients with adenomyosis and endometrium from 23 healthy controls were collected. Immunohistochemical analyses of platelet marker CD41, transforming growth factor beta 1 (TGF-β1) and vascular endothelial growth factor (VEGF) were performed to investigate aggregation and activation of platelets in the stroma. Picrosirius staining was carried out to evaluate the extent of fibrotic tissue.