The effects of diabetes mellitus include long-term damages, dysfunctions, and failures of various organs. An important complication of diabetes is the disturbance in the male reproductive system. Glucose metabolism is...The effects of diabetes mellitus include long-term damages, dysfunctions, and failures of various organs. An important complication of diabetes is the disturbance in the male reproductive system. Glucose metabolism is an important event in spermatogenesis. Moreover, glucose metabolism is also important for maintaining basic cell activity, as well as specific functions, such as motility and fertilization ability in mature sperm. Diabetic disease and experimentally induced diabetes both demonstrated that either type 1 diabetes or type 2 diabetes could have detrimental effects on male fertility, especially on sperm quality, such as sperm motility, sperm DNA integrity, and ingredients of seminal plasma. Epigenetic modifications are essential during spermatogenesis. The epigenetic regulation represents chromatin modifications including DNA methylation, histone modifications, remodeling of nucleosomes and the higher-order chromatin reorganization and noncoding RNAs. If spermatogenesis is affected during the critical developmental window, embryonic gonadal development, and germline differentiation, environmentally-induced epigenetic modifications may become permanent in the germ line epigenome and have a potential impact on subsequent generations through epigenetic transgenerational inheritance. Diabetes may influence the epigenetic modification during sperm spermatogenesis and that these epigenetic dysregulation may be inherited through the male germ line and passed onto more than one generation, which in turn may increase the risk of diabetes in offspring.展开更多
Basonuclin(BNC1)is expressed primarily in proliferative keratinocytes and gametogenic cells.However,its roles in spermatogenesis and testicular aging were not dear.Previously we discovered a heterozygous BNC1 truncati...Basonuclin(BNC1)is expressed primarily in proliferative keratinocytes and gametogenic cells.However,its roles in spermatogenesis and testicular aging were not dear.Previously we discovered a heterozygous BNC1 truncation mutation in a premature ovarian insufficiency pedigree.In this study,we found that male mice carrying the truncation mutation exhibited progressively fertility loss and testicular premature aging.Genome-wide expression profiling and direct binding studies(by chromatin immunoprecipitation sequencing)with BNC1 in mouse testis identified several spermatogenesis-specific gene promoters targeted by BNC1 including kelch-like family member 10(Klhl1O),testis expressed 14(Tex14)9 and spermatogenesis and centriole associated 1(Spatcl).Moreover,biochemical analysis showed that BNC1 was associated with TATA-box binding protein-associated factor 7 like(TAF7L),a germ cell-specific paralogue of the transcription factor IID subunit TAF7,both in vitro and in testis,suggesting that BNC1 might directly cooperate with TAF7L to regulate spermatogenesis.The truncation mutation disabled nuclear translocation of the BNC1/TAF7L complex,thus,disturbing expression of related genes and leading to testicular premature aging.Similarly,expressions of Y-box-binding protein 2(YBX2),outer dense fiber of sperm tails 1(ODfl),and glyceraldehyde-3-phosphate dehydrogenase,spermatogenic(GAPDHS)were significantly decreased in the testis of men with non-obstructive azoospermia.The present study adds to the understanding of the physiology of male reproductive aging and the mechanism of spermatogenic failure in infertile men.展开更多
文摘The effects of diabetes mellitus include long-term damages, dysfunctions, and failures of various organs. An important complication of diabetes is the disturbance in the male reproductive system. Glucose metabolism is an important event in spermatogenesis. Moreover, glucose metabolism is also important for maintaining basic cell activity, as well as specific functions, such as motility and fertilization ability in mature sperm. Diabetic disease and experimentally induced diabetes both demonstrated that either type 1 diabetes or type 2 diabetes could have detrimental effects on male fertility, especially on sperm quality, such as sperm motility, sperm DNA integrity, and ingredients of seminal plasma. Epigenetic modifications are essential during spermatogenesis. The epigenetic regulation represents chromatin modifications including DNA methylation, histone modifications, remodeling of nucleosomes and the higher-order chromatin reorganization and noncoding RNAs. If spermatogenesis is affected during the critical developmental window, embryonic gonadal development, and germline differentiation, environmentally-induced epigenetic modifications may become permanent in the germ line epigenome and have a potential impact on subsequent generations through epigenetic transgenerational inheritance. Diabetes may influence the epigenetic modification during sperm spermatogenesis and that these epigenetic dysregulation may be inherited through the male germ line and passed onto more than one generation, which in turn may increase the risk of diabetes in offspring.
基金This work was supported by the National Key Research and Development Program of China(2018YFC1005003,2017YFC1001003,and 2017YFC1001303)the National Natural Science Foundation of China(81471421,81401219,and 81701461)+3 种基金The Fundamental Research Funds for the Central Universities,Natural Science Foundation of Zhejiang Province(Q19H040040)Key Research Program of Zhejiang Provincial Natural Science Foundation(LZ18H040001)Municipal Human Resources Development Program for Outstanding Young Talents in Medical and Health Sciences in Shanghai(2018YQ39)Zhejiang University Education Foundation Global Partnership Fund.
文摘Basonuclin(BNC1)is expressed primarily in proliferative keratinocytes and gametogenic cells.However,its roles in spermatogenesis and testicular aging were not dear.Previously we discovered a heterozygous BNC1 truncation mutation in a premature ovarian insufficiency pedigree.In this study,we found that male mice carrying the truncation mutation exhibited progressively fertility loss and testicular premature aging.Genome-wide expression profiling and direct binding studies(by chromatin immunoprecipitation sequencing)with BNC1 in mouse testis identified several spermatogenesis-specific gene promoters targeted by BNC1 including kelch-like family member 10(Klhl1O),testis expressed 14(Tex14)9 and spermatogenesis and centriole associated 1(Spatcl).Moreover,biochemical analysis showed that BNC1 was associated with TATA-box binding protein-associated factor 7 like(TAF7L),a germ cell-specific paralogue of the transcription factor IID subunit TAF7,both in vitro and in testis,suggesting that BNC1 might directly cooperate with TAF7L to regulate spermatogenesis.The truncation mutation disabled nuclear translocation of the BNC1/TAF7L complex,thus,disturbing expression of related genes and leading to testicular premature aging.Similarly,expressions of Y-box-binding protein 2(YBX2),outer dense fiber of sperm tails 1(ODfl),and glyceraldehyde-3-phosphate dehydrogenase,spermatogenic(GAPDHS)were significantly decreased in the testis of men with non-obstructive azoospermia.The present study adds to the understanding of the physiology of male reproductive aging and the mechanism of spermatogenic failure in infertile men.