Recent data from several laboratories have provided evidence that the newly fertilized oocyte inherits epigenetic signals from the sperm chromatin that are required for proper embryonic development. For the purposes o...Recent data from several laboratories have provided evidence that the newly fertilized oocyte inherits epigenetic signals from the sperm chromatin that are required for proper embryonic development. For the purposes of this review, the term epigenetic is used to describe all types of molecular information that are transmitted from the sperm cell to the embryo. There are at least six different forms of epigenetic information that have already been established as being required for proper embryogenesis in mammals or for which there is evidence that it may do so. These are (i) DNA methylation; (ii) sperm-specific histones, (iii) other chromatin-associated proteins; (iv) the perinuclear theca proteins; (v) sperm-born RNAs and, the focus of this review; and (vi) the DNA loop domain organization by the sperm nuclear matrix. These epigenetic signals should he considered when designing protocols for the manipulation and cryopreservation of spermatozoa for assisted reproductive technology as necessary components for effective fertilization and subsequent embryo development.展开更多
RNA binding proteins have long been known to play a role in spermatogenesis. The laboratory of Norman Hecht was one of the leaders in this field, having characterized three RNA binding proteins that regulate mRNAs dur...RNA binding proteins have long been known to play a role in spermatogenesis. The laboratory of Norman Hecht was one of the leaders in this field, having characterized three RNA binding proteins that regulate mRNAs during sperm differentiation. Polypyrimidine tract-binding pro- tein 2 (PTB2) has two functions--stabilizing mRNA transcripts in the cytoplasm and being involved in splicing,l Using in vivo cross- linking of protein to RNA, several mRNA and small RNA targets were identified in the testis.2 Translin is another protein that both stabilizes mRNAs from a specific transcription factor, and is associated with small RNAs.3 Perhaps the most interesting is the DNA/RNA binding protein MSY2. At low concentrations,展开更多
The highly condensed chromatin of mammalian spermatozoa is usually considered to be biologically inert before fertilization. However, we have demonstrated that even in this compacted state, sperm chromatin is subject ...The highly condensed chromatin of mammalian spermatozoa is usually considered to be biologically inert before fertilization. However, we have demonstrated that even in this compacted state, sperm chromatin is subject to degradation at open configurations associated with the nuclear matrix through a process we have termed sperm chromatin fragmentation (SCF). "[his suggests that a mechanism exists to monitor the health of spermatozoa during transit through the male reproductive tract and to destroy the genome of defective sperm cells. The site of DNA damage in SCF, the matrix attachment sites, are the same that we hypothesize initiate DNA synthesis in the zygote. When sperm that have damaged DNA are injected into the oocyte, the newly created zygote responds by delaying DNA synthesis in the male pronudeus and, if the damage is severe enough, arresting the embryo's development. Here we present a model for paternal DNA regulation by the nuclear matrix that begins during sperm maturation and continues through early embryonic development.展开更多
文摘Recent data from several laboratories have provided evidence that the newly fertilized oocyte inherits epigenetic signals from the sperm chromatin that are required for proper embryonic development. For the purposes of this review, the term epigenetic is used to describe all types of molecular information that are transmitted from the sperm cell to the embryo. There are at least six different forms of epigenetic information that have already been established as being required for proper embryogenesis in mammals or for which there is evidence that it may do so. These are (i) DNA methylation; (ii) sperm-specific histones, (iii) other chromatin-associated proteins; (iv) the perinuclear theca proteins; (v) sperm-born RNAs and, the focus of this review; and (vi) the DNA loop domain organization by the sperm nuclear matrix. These epigenetic signals should he considered when designing protocols for the manipulation and cryopreservation of spermatozoa for assisted reproductive technology as necessary components for effective fertilization and subsequent embryo development.
文摘RNA binding proteins have long been known to play a role in spermatogenesis. The laboratory of Norman Hecht was one of the leaders in this field, having characterized three RNA binding proteins that regulate mRNAs during sperm differentiation. Polypyrimidine tract-binding pro- tein 2 (PTB2) has two functions--stabilizing mRNA transcripts in the cytoplasm and being involved in splicing,l Using in vivo cross- linking of protein to RNA, several mRNA and small RNA targets were identified in the testis.2 Translin is another protein that both stabilizes mRNAs from a specific transcription factor, and is associated with small RNAs.3 Perhaps the most interesting is the DNA/RNA binding protein MSY2. At low concentrations,
文摘The highly condensed chromatin of mammalian spermatozoa is usually considered to be biologically inert before fertilization. However, we have demonstrated that even in this compacted state, sperm chromatin is subject to degradation at open configurations associated with the nuclear matrix through a process we have termed sperm chromatin fragmentation (SCF). "[his suggests that a mechanism exists to monitor the health of spermatozoa during transit through the male reproductive tract and to destroy the genome of defective sperm cells. The site of DNA damage in SCF, the matrix attachment sites, are the same that we hypothesize initiate DNA synthesis in the zygote. When sperm that have damaged DNA are injected into the oocyte, the newly created zygote responds by delaying DNA synthesis in the male pronudeus and, if the damage is severe enough, arresting the embryo's development. Here we present a model for paternal DNA regulation by the nuclear matrix that begins during sperm maturation and continues through early embryonic development.