Researchers have successfully developed a uterine tissue-specific hydrogel for endometrial regeneration, thus aiding in pregnancy success for infertile cis women.
According to the World Health Organization, roughly 1 in 6 adults worldwide suffer from infertility. Given the stigma surrounding infertility and the sheer proportion of people affected by it, there is an urgent need to increase access to affordable and high-quality treatments for those in need.
For cis women, a successful pregnancy hinges on a healthy endometrium that is mainly characterised by adequate thickness. A thin endometrium (thickness less than 7mm) has been widely reported to be correlated with failed embryo implantation and a high chance of miscarriage. Currently, treatment options for female infertility include hormonal therapy and intrauterine injections with growth factors. However, these treatments show limited clinical success.
Another possible treatment route is through tissue regeneration of the endometrium using decellularised extracellular matrix (dECMs). Decellularised extracellular matrix (dECMs) are biological scaffolds that have had their cellular components removed. Essentially, dECM is the non-cellular component of tissues that provides mechanical support, regulates cell behaviour, and facilitates tissue development and regeneration. Although the past three decades have shown great promise in the biomedical applications of dECM-based hydrogels in the regeneration of various tissues and organs, including the heart, kidney, bone, and skin, investigations into the use of dECMs in the uterus are still in its infancy.
Advancing knowledge in this field is a joint research team from Pohang University and CHA University in South Korea. Led by Professor Dong-Woo Cho, Professor Youn-Jung Kang, and Professor Jinah Jang, the team developed hydrogels containing uterus-derived decellularised extracellular matrix (UdECM) that are able to regenerate the endometrium. Their findings were published in Advanced Functional Materials.
Like all tissue-specific dECMs, the researchers developed the UdECM hydrogel so that it resembles the innate microenvironments of the original uterine tissue. They then tested the efficiency of the hydrogels on murine models with thin endometrium and human endometrial tissues. When injected, the hydrogel significantly increased the thickness of the whole endometrium and promoted the number of blood vessels in the area, creating a favourable environment for embryo implantation. In addition, the hydrogel has low toxicity and ensures a 90% survival rate for implanted embryos. Taken together, the findings demonstrated the effectiveness and therapeutic potential of UdECMs in enhancing the fertility outcomes of cis women with thin endometrium.
Using computational biology methods, the researchers were also able to elucidate the molecular mechanism by which endometrial regeneration occurs. Specifically, they found that the gene IGFBP3 is highly expressed in the endometrium during the period right after implantation, suggesting that it plays an essential role in endometrial remodelling and the formation of the placental bed.
Aside from murine models and tissue cultures, the researchers also studied the performance of the UdECM hydrogels on human endometrial tissues obtained from three different infertile patients. To validate the effectiveness of UdECM-mediated endometrial regeneration on human endometrial tissues, changes in the expression levels of targeted genes were monitored. The results revealed that UdECMs with different origins showed differing therapeutic effects depending on the endometrial conditions of the patient, suggesting their use as a therapeutic intervention for personalised regenerative medicine.
Overall, the authors are hopeful that their pioneering research will act as the foundation for further studies addressing the clinical applicability of UdECMs and consequently lead to the identification of new treatment options for infertility patients with poor uterine environments. [APBN]
Source: Ahn et al. (2023). Uterus‐Derived Decellularized Extracellular Matrix‐Mediated Endometrial Regeneration and Fertility Enhancement. Advanced Functional Materials, 2214291. https://doi.org/10.1002/adfm.202214291