The reduction or loss of female fertility has become a major health issue. Preserving female fertility has been a central area of research since cryobiology's inception, addressing the cryopreservation of oocytes, embryos, ovary tissues, and others. Since follicles are rich in sources, easy to obtain, and generally do not involve complicated ethical issues, their cryopreservation is a promising supplement to the current fertility preservation approaches. Particularly for prepubescent girls and women in urgent need of cancer treatment, cryopreservation of ovarian tissue containing healthy follicles is the only option. However, the conventional cryopreservation methods require a high concentration of cryoprotectants (up to 6M), causing high toxicity to the specimens, leading to sophisticated operation protocols but poor recovery of fertility functions after preservation.
Recently, Professor Gang Zhao from the University of Science and Technology of China, a long-term member and a previous Governor (2015-2017, 2019-2021) of the Society for Cryobiology, and his collaborators successfully cryopreserved mouse follicles based on synergistic ice suppression effects by applying structural bionics and novel technologies. This work has important applications for follicle-based female fertility preservation. Relevant research results were recently published in Nature Communications.
The Cryo-biomedical Engineering research team from the University of Science and Technology of China and Anhui Medical University developed a method for the vitrification of mouse follicles with a low concentration of cryoprotectant based on a synergistic ice suppression strategy. Overall, this study established an integrated platform that integrates microencapsulation, freezing, rewarming, and 3D culturing, thus providing a unique solution for the preservation and utilization of follicles.
They combined microencapsulation with hydrogel, magnetothermal and photothermal space rewarming to achieve synergistic ice suppression, avoid devitrification/recrystallization during rewarming, and reduce the concentration of penetrating cryoprotectants by 75% (only about 25% of the normal concentration used in follicle vitrification). Compared to the conventional water bath warming, the viability of preantral follicles was increased by 33%. Moreover, the cavity formation rate of preantral follicles after in vitro culture was comparable to the control group without vitrification. Furthermore, the percentage of MII oocytes developed from the vitrified follicles, and the birth rate of offspring following in vitro fertilization and embryo transfer were also similar to the control group. This work provides a step towards nontoxic vitrification of follicles by utilizing the synergistic cryoprotective effects of microencapsulation and nanowarming.
Dr. Zhao explained, “Magnetothermal and photothermal spatial rewarming technology can effectively improve the rewarming rate and temperature uniformity, inhibit possible devitrification/recrystallization during rewarming, and avoid excessive cell damage. Hydrogel encapsulation can not only provide regulation of the key biochemical and mechanical microenvironments, and support the in vitro 3D development of mouse follicles after rewarming, but also provide cryoprotection and reduce the demand for cryoprotectants. It can also achieve the protection of follicles from contacting the magnetocaloric and photothermal materials to enhance the biosafety." Dr. Zhao added, "The relevant technologies are expected to be applied clinically in the local hospitals within the next few years."
This work also perfectly demonstrates that cryopreservation is a unique subject of converging science and technology, facilitating transdisciplinary integration of life sciences, physics, chemistry, engineering, and beyond to address complex problems.