During mouse gametogenesis, germ cells derived from the same progenitor are connected via intercellular bridges forming germline cysts, within which asymmetrical or symmetrical cell fate occurs in female and male germ cells, respectively. Here, we have identified branched cyst structures in mice, and investigated their formation and function in oocyte determination. In fetal female cysts, 16.8% of the germ cells are connected by three or four bridges, namely branching germ cells. These germ cells are preferentially protected from cell death and cyst fragmentation and accumulate cytoplasm and organelles from sister germ cells to become primary oocytes. Changes in cyst structure and differential cell volumes among cyst germ cells suggest that cytoplasmic transport in germline cysts is conducted in a directional manner, in which cellular content is first transported locally between peripheral germ cells and further enriched in branching germ cells, a process causing selective germ cell loss in cysts. Cyst fragmentation occurs extensively in female cysts, but not in male cysts. Male cysts in fetal and adult testes have branched cyst structures, without differential cell fates between germ cells. During fetal cyst formation, E-cadherin (E-cad) junctions between germ cells position intercellular bridges to form branched cysts. Disrupted junction formation in E-cad-depleted cysts led to an altered ratio in branched cysts. Germ cell-specific E-cad knockout resulted in reductions in primary oocyte number and oocyte size. These findings shed light on how oocyte fate is determined within mouse germline cysts.

In mammalian females, the transition from dormancy in primordial follicles to follicular development is critical for maintaining ovarian function and reproductive longevity. In mice, the quiescent primary oocyte of the primordial follicle contains a Balbiani body (B-body), an organelle aggregate comprised of a spherical structure of Golgi complexes. Here we show that the structure of the B-body is maintained by microtubules and actin. The B-body stores mRNA-capping enzyme and 597 mRNAs associated with mRNA-decapping enzyme 1 A (DCP1A). Gene ontology analysis results indicate that proteins encoded by these mRNAs function in enzyme binding, cellular component organization and packing of telomere ends. Pharmacological depolymerization of microtubules or actin led to B-body disassociation and nascent protein synthesis around the dissociated B-bodies within three hours. An increased number of activated developing follicles were observed in ovaries with prolonged culture and the in vivo mouse model. Our results indicate that the mouse B-body is involved in the activation of dormant primordial follicles likely via translation of the B-body-associated RNAs in primary oocytes.

The interaction between CD47 expressed on cancer cells and signal regulatory protein-α located on macrophages blocks the phagocytosis of tumor cells by macrophages. Our data reveal that human endometrial cancer cells (hECCs) upregulate the CD47 level on their surface and that there is a high density of tumor-associated macrophages within the microenvironment of human endometrial cancer. In vitro functional assay shows that an anti-CD47 monoclonal antibody (mAb) promotes the phagocytosis of hECCs by macrophages. Systemic and in situ treatments with an anti-CD47 mAb effectively reduce tumor burden in vivo in a genetically engineered mouse model of endometrial cancer. Thus, this study provides preclinical evidence that CD47 blockade using an anti-CD47 mAb to augment macrophage phagocytosis is a potential therapeutic strategy for endometrial cancer.

Objective: The purpose of this study is to determine how family history of cancer, genetic mutations, presenting symptoms, and comorbidity burden collectively influence cancer outcomes in patients with epithelial ovarian cancer. Methods: A retrospective analysis was conducted on all patients with epithelial ovarian cancer treated at the University of Missouri and Ellis Fischel Cancer Center between 2008 and 2024. Patient charts were reviewed for histological subtypes, stage of cancer, status of metastasis, CA-125 values, presenting symptoms, comorbidities, family history of cancer, genetic mutations, and survival outcome. Cox regression and association analyses were performed. Results: In this cohort of patients, comorbidities and genetic mutations did not influence ovarian cancer survival. While histological subtypes, CA-125 levels, and cancer stage remained strongly associated with survival. Significant associations were observed between certain presenting symptoms and cancer histological subtype, a family history of breast cancer, stage of cancer at diagnosis, the status of metastasis, and CA-125 levels. Conclusion: Comorbidities and genetic mutations were not significantly associated with ovarian cancer survival. Presenting symptoms were associated with several clinical and pathological variables linked to ovarian cancer diagnosis.