Biology subjects

Zelinski, M.

Publications and source records attributed to Zelinski, M..

3 recordsLinked to original sources

bioRxiv2025

Exploring the Dynamics of Follicle Development and Hormone Synthesis: The Role of Oxygen Tension in Rhesus Macaque Follicle Culture

In vitro culture of cryopreserved ovarian follicles has the potential to extend fertility options for young women seeking to preserve ovarian tissue prior to undergoing cancer treatments. Successful implementation of this strategy has been elusive and likely requires a more complete understanding of the microenvironment of the developing ovarian follicles, including ovarian oxygen concentrations. The oxygen tension within the reproductive tract plays a crucial role in follicular development and oocyte maturation. While in vitro culture systems often use atmospheric oxygen (21%), the native environment in vivo is significantly lower, ranging from 1.5% to 8.7%. This study aimed to investigate the effects of reduced oxygen tensions (3% and 5%) on follicle survival, growth, antrum formation, and hormone production in cultured secondary follicles from rhesus macaques (macaca mulata). A total of 300 follicles were isolated from 7 animals and cultured under three oxygen conditions: 3%, 5%, and 21% O2. Follicle survival and antrum formation were assessed weekly by microscopy and Kaplan-Meier survival analysis, while growth dynamics and hormone levels (estradiol, progesterone, AMH, and inhibin B) were monitored throughout the culture period. Results demonstrated that follicles cultured at 3% and 5% oxygen exhibited significantly higher survival rates and antrum formation compared to those cultured at 21% O2. No significant differences in survival were observed between the 3% and 5% oxygen groups. Growth dynamics revealed distinct patterns, with both low oxygen groups promoting more robust and sustained follicle growth, while atmospheric oxygen led to rapid degeneration. Hormonal analysis showed that follicles in 21% O2 had elevated early hormone production but exhibited reduced long-term viability. In contrast, 3% and 5% oxygen delayed hormone production, reflecting a more stable and sustained follicular environment. These findings underscore the importance of low oxygen tensions in mimicking the physiological conditions of the reproductive tract, improving follicular development, and supporting optimal hormonal function in vitro. This study suggests that further reducing oxygen levels to 3% may offer additional advantages for long-term follicle viability and function in reproductive technologies. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=71 SRC="FIGDIR/small/652505v1_ufig1.gif" ALT="Figure 1"> View larger version (17K): org.highwire.dtl.DTLVardef@11fcb62org.highwire.dtl.DTLVardef@61c0beorg.highwire.dtl.DTLVardef@1b5328forg.highwire.dtl.DTLVardef@10a7538_HPS_FORMAT_FIGEXP M_FIG C_FIG

developmental biology↗

bioRxiv2024

Self-organizing ovarian somatic organoids preserve cellular heterogeneity and reveal cellular contributions to ovarian aging

Ovarian somatic cells are essential for reproductive function, but no existing ex vivo models recapitulate the cellular heterogeneity or interactions within this compartment. We engineered a novel ovarian somatic organoid model by culturing a stroma-enriched fraction of mouse ovaries in scaffold-free agarose micromolds. Ovarian somatic organoids self-organized, maintained diverse cell populations, produced extracellular matrix, and secreted hormones. Organoids generated from reproductively old mice exhibited reduced aggregation and growth compared to young counterparts, as well as differences in cellular composition. Interestingly, matrix fibroblasts from old mice demonstrated upregulation of pathways associated with the actin cytoskeleton and downregulation of cell adhesion pathways, indicative of increased cellular stiffness which may impair organoid aggregation. Cellular morphology, which is regulated by the cytoskeleton, significantly changed with age and in response to actin depolymerization. Moreover, actin depolymerization rescued age-associated organoid aggregation deficiency. Overall, ovarian somatic organoids have advanced fundamental knowledge of cellular contributions to ovarian aging.

cell 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↗