There have been tremendous advances in both the diagnosis and treatment of male factor infertility; however, the mechanisms responsible to recreate spermatogenesis outside of the testicular environment continue to elu...There have been tremendous advances in both the diagnosis and treatment of male factor infertility; however, the mechanisms responsible to recreate spermatogenesis outside of the testicular environment continue to elude andrologists. Having the ability to ＇grow＇ human sperm would be a tremendous advance in reproductive biology with multiple possible clinical applications, such as a treatment option for men with testicular failure and azoospermia of multiple etiologies. To understand the complexities of human spermatogenesis in a research environment, model systems have been designed with the intent to replicate the testicular microenvironment. Currently, there are both in vivoand in vitro model systems. In vivo model systems involve the transplantation of either spermatogonial stem cells or testicular xenographs. In vitro model systems involve the use of pluripotent stem cells and complex coculturing and/or three-dimensional culturing techniques. This review discusses the basic methodologies, possible clinical applications, benefits and limitations of each model system. Although these model systems have greatly improved our understanding of human spermatogenesis, we unfortunately have not been successful in demonstrating complete human spermatogenesis outside of the testicle.展开更多
For men struggling to conceive with their partners, diagnostic tools are limited and often consist of only a standard semen analysis. This baseline test serves as a crude estimation of male fertility, leaving patients...For men struggling to conceive with their partners, diagnostic tools are limited and often consist of only a standard semen analysis. This baseline test serves as a crude estimation of male fertility, leaving patients and clinicians in need of additional diagnostic biomarkers. Seminal fluid contains the highest concentration of molecules from the male reproductive glands, therefore, this review focuses on current and novel seminal biomarkers in certain male infertility scenarios, including natural fertility, differentiating azoospermia etiologies, and predicting assisted reproductive technique success. Currently available tests include antisperm antibody assays, DNA fragmentation index, sperm fluorescence in situ hybridization, and other historical sperm functional tests. The poor diagnostic ability of current assays has led to continued efforts to find more predictive biomarkers. Emerging research in the fields of genomics, epigenetics, proteomics, transcriptomics, and metabolomics holds promise for the development of novel male infertility biomarkers. Seminal protein-based assays of TEXI01, ECM 1, and ACRV1 are already available or under final development for clinical use. Additional panels of DNA, RNA, proteins, or metabolites are being explored as we attempt to understand the pathophysiologic processes of male infertility. Future ventures will need to continue data integration and validation for the development of clinically useful infertility biomarkers to aid in male infertility diagnosis, treatment, and counseling.展开更多
文摘There have been tremendous advances in both the diagnosis and treatment of male factor infertility; however, the mechanisms responsible to recreate spermatogenesis outside of the testicular environment continue to elude andrologists. Having the ability to ＇grow＇ human sperm would be a tremendous advance in reproductive biology with multiple possible clinical applications, such as a treatment option for men with testicular failure and azoospermia of multiple etiologies. To understand the complexities of human spermatogenesis in a research environment, model systems have been designed with the intent to replicate the testicular microenvironment. Currently, there are both in vivoand in vitro model systems. In vivo model systems involve the transplantation of either spermatogonial stem cells or testicular xenographs. In vitro model systems involve the use of pluripotent stem cells and complex coculturing and/or three-dimensional culturing techniques. This review discusses the basic methodologies, possible clinical applications, benefits and limitations of each model system. Although these model systems have greatly improved our understanding of human spermatogenesis, we unfortunately have not been successful in demonstrating complete human spermatogenesis outside of the testicle.
文摘For men struggling to conceive with their partners, diagnostic tools are limited and often consist of only a standard semen analysis. This baseline test serves as a crude estimation of male fertility, leaving patients and clinicians in need of additional diagnostic biomarkers. Seminal fluid contains the highest concentration of molecules from the male reproductive glands, therefore, this review focuses on current and novel seminal biomarkers in certain male infertility scenarios, including natural fertility, differentiating azoospermia etiologies, and predicting assisted reproductive technique success. Currently available tests include antisperm antibody assays, DNA fragmentation index, sperm fluorescence in situ hybridization, and other historical sperm functional tests. The poor diagnostic ability of current assays has led to continued efforts to find more predictive biomarkers. Emerging research in the fields of genomics, epigenetics, proteomics, transcriptomics, and metabolomics holds promise for the development of novel male infertility biomarkers. Seminal protein-based assays of TEXI01, ECM 1, and ACRV1 are already available or under final development for clinical use. Additional panels of DNA, RNA, proteins, or metabolites are being explored as we attempt to understand the pathophysiologic processes of male infertility. Future ventures will need to continue data integration and validation for the development of clinically useful infertility biomarkers to aid in male infertility diagnosis, treatment, and counseling.
