Shikanov, A. | Search bioRxiv

bioRxiv2021

Cellular heterogeneity of human fallopian tubes in normal and hydrosalpinx disease states identified by scRNA-seq

Fallopian tube (FT) homeostasis requires dynamic regulation of heterogeneous cell populations and is disrupted in infertility and ovarian cancer. Here we applied single-cell RNAseq to profile 53,376 FT cells from 3 healthy pre-menopausal subjects. The resulting cell atlas contains 12 major cell types representing epithelial, stromal and immune compartments. Re-clustering of epithelial cells identified 4 ciliated and 6 non-ciliated secretory epithelial subtypes, two of which represent potential progenitor pools: one leading to mature secretory cells, while the other contributing to either ciliated cells or one of the stromal cell types. To understand how FT cell numbers and states change in a disease state, we analyzed ~15,000 cells from a hydrosalpinx sample and observed shifts in epithelial and stromal populations, and cell type-specific changes in extracellular matrix and TGF-{beta} signaling, underscoring fibrosis pathophysiology. This resource is expected to facilitate future studies to understand fallopian tube homeostasis in normal development and disease.

systems biology↗

bioRxiv2021

Encapsulated allografts preclude host sensitization and promote ovarian endocrine function in ovariectomized young rhesus monkeys and sensitized mice

Transplantation of allogeneic donor ovarian tissue holds great potential for female cancer survivors who often experience premature ovarian insufficiency. To avoid complications associated with immune suppression and to protect transplanted ovarian allografts from immune-mediated injury, we have developed an immuno-isolating hydrogel-based capsule that supports the function of ovarian allografts without triggering an immune response. Encapsulated ovarian allografts implanted in naive ovariectomized BALB/c mice responded to the circulating gonadotropins without direct revascularization and maintained function for 4 months, as evident by regular estrous cycles and presence of antral follicles in the retrieved grafts. Repeated implantations of encapsulated mouse ovarian allografts did not sensitize naive BALB/c mice in contrast to non-encapsulated controls, which was confirmed with undetectable levels of allo-antibody. Further, encapsulated allografts implanted in hosts previously sensitized by implantation of non-encapsulated allografts restored estrous cycles similarly to our results in naive recipients. Next, we tested the translational potential and efficiency of the immune-isolating capsule in a rhesus monkey model by implanting encapsulated ovarian auto- and allografts in young ovariectomized animals. The encapsulated ovarian grafts survived and restored basal levels of urinary estrone conjugate and pregnanediol 3-glucuronide during the approximate 4-5 month observation period. We demonstrate, for the first time, that encapsulation of ovarian allografts prevents sensitization and protects the allograft from rejection in young rhesus monkeys and in sensitized mice.

bioengineering↗