| 摘要: | Osteopontin (OPN), an extracellular phosphorylated glycoprotein, was initially identified in the extracellular protein layer of bone tissue. Due to the capability of stimulating the expression of adhesion molecules and contributing to inflammation activity, OPN has been proposed to contribute to the process of implanting embryos. Our study demonstrates that OPN supplementation at an appropriate level can enhance mouse embryo development and implantation ability, via interacting with αvβ3 integrin and RGS2 pathway. In validation on in vitro trophoblast-like cells, OPN overexpression promoted migration and increased cell spheroid size via proliferation. Mouse embryos supplemented with OPN enhanced the potency for implantation in mice, which was then validated on spheroid adhesion assay with JAR cells. These findings suggest that OPN has the potential as a supplement in in vitro embryo culture to improve embryo implantation in embryology laboratory settings.
Additionally, an excessive expression of OPN and its isoforms was detected in the ectopic endometriosis tissue. The involvement of OPN and its isoforms in the pathogenesis of endometriosis was mediated through the PI3K and NF-?B signaling pathways. Notably, while OPNb was primarily implicated in enhanced cell proliferation, the selective overexpression of OPNc was strongly linked with a marked enhancement in migratory ability. Intriguingly, a decrease in both serum and tissue levels of OPN was observed following treatment with gonadotropin-releasing hormone agonist (GnRHa). OPN has manifested multifaceted roles across diverse biological contexts, exerting significant effects on both embryo implantation and the pathogenesis of endometriosis in women. Meanwhile, OPN has the potential of a target for endometriosis management, as well as a useful marker for monitoring treatment response in patients suffering from endometriotic diseases.
Based on the observation that OPN can be partially inhibited by GnRHa, we were further to verify whether GnRHa could mitigate the deleterious effects of endometriosis on female reproductive function. A retrospective study was conducted on infertile patients with ovarian endometriosis who were recommended for frozen embryo transfer (FET). The study revealed that patients who received GnRHa pretreatment exhibited improved pregnancy rates and embryo implantation outcomes.
Despite the favorable results, there is no consensus on the effectiveness of GnRHa pretreatment in the frozen-thawed embryo transfer (FET) cycles. Our objective was to investigate the impact of GnRHa on FET cycles, focusing on its effect on women with endometriosis in particular, as well as infertile women in general, through a systematic review and meta-analysis. The meta-analysis demonstrated that GnRHa pretreatment improved pregnancy outcomes of FET cycles in the patients undergoing FET, including embryo implantation and live birth rates, particularly when a long-term pituitary suppression strategy and depot GnRHa protocol were used.
In summary, this work has shed light on the multifaceted role of OPN in reproductive biology, including its involvement in embryonic implantation and endometriosis, as well as the potential benefits of using GnRHa in frozen-thawed embryo transfer (FET) cycles. The findings provide new insights into the underlying mechanisms of reproductive disorders and offer promising strategies for managing infertility in women with endometriosis and adenomyosis. |
