DMOG Enhances hUC-MSCs Paracrine Activity to Promote Endometrial Epithelial Cells Reconstitution Via VSELs Formation
Anfeng Ning1,2,3,4,5,6, Nansong Xiao1,2, Zi Chen1,2
1Reproductive and Genetic Center & NHC Key Laboratory of Reproductive Health Engineering Technology Research, National Research Institute for Family Planning (NRIFP), Beijing, 100081, China.
Abstract:
Estrogen deficiency-induced uterine atrophy is a major cause of menstrual disorders and infertility in postmenopausal women and patients with premature ovarian failure. However, current hormone replacement therapies carry long-term risks and fail to achieve physiological endometrial regeneration. It has been demonstrated that dimethyloxalylglycine (DMOG) can augment the therapeutic effects of mesenchymal stem cells (MSCs), but the effects of DMOG-pretreated MSCs on Estrogen deficiency-induced uterine atrophy remain unclear. This study aimed to explore whether DMOG-pretreated human umbilical cord MSCs (hUC-MSCs) could repair estrogen deficiency-induced uterine atrophy. The results showed that compared with the MSCs group, the DM group significantly improved the disordered estrous cycle of ovariectomy (OVX) mice, increased serum estradiol (E2) levels, and restored uterine morphology and index, and facilitated the recovery of endometrial thickness and gland number. Masson staining confirmed that the DM group had a more significant reduction in endometrial fibrosis. Immunofluorescence demonstrated enhanced expression of Oct-4 and Nanog in the DM group, which suggests that DMOG-pretreated hUC-MSCs may exert paracrine effects to promote the formation of VSELs, thereby facilitating the remodeling of endometrial epithelial structure. This provides a novel and effective strategy for the treatment of estrogen deficiency-related uterine atrophy.
