Loss of Maternal CTCF Is Associated with Peri-Implantation Lethality of Ctcf Null Embryos

CTCF is a highly conserved, multifunctional zinc finger protein involved in critical aspects of gene regulation including transcription regulation, chromatin insulation, genomic imprinting, X-chromosome inactivation, and higher order chromatin organization. Such multifunctional properties of CTCF suggest an essential role in development. Indeed, a previous report on maternal depletion of CTCF suggested that CTCF is essential for pre-implantation development. To distinguish between the effects of maternal and zygotic expression of CTCF, we studied pre-implantation development in mice harboring a complete loss of function Ctcf knockout allele. Although we demonstrated that homozygous deletion of Ctcf is early embryonically lethal, in contrast to previous observations, we showed that the Ctcf nullizygous embryos developed up to the blastocyst stage (E3.5) followed by peri-implantation lethality (E4.5–E5.5). Moreover, one-cell stage Ctcf nullizygous embryos cultured ex vivo developed to the 16–32 cell stage with no obvious abnormalities. Using a single embryo assay that allowed both genotype and mRNA expression analyses of the same embryo, we demonstrated that pre-implantation development of the Ctcf nullizygous embryos was associated with the retention of the maternal wild type Ctcf mRNA. Loss of this stable maternal transcript was temporally associated with loss of CTCF protein expression, apoptosis of the developing embryo, and failure to further develop an inner cell mass and trophoectoderm ex vivo. This indicates that CTCF expression is critical to early embryogenesis and loss of its expression rapidly leads to apoptosis at a very early developmental stage. This is the first study documenting the presence of the stable maternal Ctcf transcript in the blastocyst stage embryos. Furthermore, in the presence of maternal CTCF, zygotic CTCF expression does not seem to be required for pre-implantation development

Sperm preservation in transgender patients

Hormonal and surgical treatments for transgender people have a deleterious effect on the possibility for these patients to reproduce. Additionally, transgender people tend to start sex reassignment treatment at a young age, when reproductive wishes are not yet clearly defined nor fulfilled. The most recent Standards of Care of the World Professional Association for Transgender Health recommend clearly informing patients regarding their future reproductive options prior to initiation of treatment. This chapter gives an overview of the current knowledge and state-of-the-art techniques in the field of fertility preservation for transgender people. Where gonadectomy definitely results in sterility, hormone therapy on the other hand also has an important, but partially reversible impact on fertility. The fertility preservation options for transgender women include the freezing of sperm collected through ejaculation or direct testicular extraction and the freezing of immature testicular tissue. Although certain fertility preservation techniques could be applicable in a standardized manner based on clear biological criteria, the technique that eventually will be performed should be the preferred choice of the patient after extended explanation of all possible options, and is highly dependent on the sex of the partner and national legislation