Gender and the Genome最新文献

Sex chromosome gene dosage compensation is required to ensure equivalent levels of X-linked gene expression between males (46, XY) and females (46, XX). To achieve similar expression, X-chromosome inactivation (XCI) is initiated in female cells during early stages of embryogenesis. Within each cell, either the maternal or paternal X chromosome is selected for whole chromosome transcriptional silencing, which is initiated and maintained by epigenetic and chromatin conformation mechanisms. With the emergence of small-molecule epigenetic inhibitors for the treatment of disease, such as cancer, the epigenetic mechanism underlying XCI may be inadvertently targeted. Here, we test 2 small-molecule epigenetic inhibitors being used clinically, GSK126 (a histone H3 lysine 27 methyltransferase inhibitor) and suberoylanilide hydroxamic acid (a histone deacetylase inhibitor), on their effects of the inactive X (Xi) in healthy human female fibroblasts. The combination of these modifiers, at subcancer therapeutic levels, leads to the inability to detect the repressive H3K27me3 modification characteristic of XCI in the majority of the cells. Importantly, genes positioned near the X-inactivation center (Xic), where inactivation is initiated, exhibit robust expression with treatment of the inhibitors, while genes located near the distal ends of the X chromosome intriguingly exhibit significant downregulation. These results demonstrate that small-molecule epigenetic inhibitors can have profound consequences on XCI in human cells, and they underscore the importance of considering gender when developing and clinically testing small-molecule epigenetic inhibitors, in particular those that target the well-characterized mechanisms of X inactivation.

In 2015 the United Kingdom (UK) became the first nation to legalize egg and zygotic nuclear transfer procedures using mitochondrial replacement techniques (MRTs) to prevent the maternal transmission of serious mitochondrial DNA diseases to offspring. These techniques are a form of human germline genetic modification and can happen intentionally if female embryos are selected during the MRT clinical process, either through sperm selection or preimplantation genetic diagnosis (PGD). In the same year, an MRT was performed by a United States (U.S.)-based physician team. This experiment involved a cross-border effort: the MRT procedure per se was carried out in the US, and the embryo transfer in Mexico. The authors examine the ethics of MRTs from the standpoint of genetic relatedness and gender implications, in places that lack adequate laws and regulation regarding assisted reproduction. Then, we briefly examine whether MRTs can be justified as a reproductive option in the US and Mexico, after reassessing their legalization in the UK. We contend that morally inadequate and ineffective regulations regarding egg donation, PGD, and germline genetic modifications jeopardize the ethical acceptability of the implementation of MRTs, suggesting that MRTs are currently difficult to justify in the US and Mexico. In addition to relevant regulation, the initiation and appropriate use of MRTs in a country require a child-centered follow-up policy and more evidence for its safety.

Parental care is among the most profound behavior expressed by humans and other animals. Despite intense interest in understanding the biological basis of parental behaviors, it remains unknown how much of parenting is encoded by the genome and which abilities instead are learned or can be refined by experience. One critical factor at the intersection between innate behaviors and experience-dependent learning is oxytocin, a neurohormone important for maternal physiology and neuroplasticity. Oxytocin acts throughout the body and brain to promote prosocial and maternal behaviors and modulates synaptic transmission to affect neural circuit dynamics. Recently we developed specific antibodies to mouse oxytocin receptors, found that oxytocin receptors are left lateralized in female auditory cortex, and examined how oxytocin enables maternal behavior by sensitizing the cortex to infant distress sounds. In this study we compare oxytocin receptor expression and function in male and female mice. Receptor expression is higher in adult female left auditory cortex than in right auditory cortex or males. Developmental profiles and mRNA expression were comparable between males and females. Behaviorally, male and female mice began expressing parental behavior similarly after cohousing with experienced females; however, oxytocin enhanced parental behavior onset in females but not males. This suggests that left lateralization of oxytocin receptor expression in females provides a mechanism for accelerating maternal behavior onset, although male mice can also effectively co-parent after experience with infants. The sex-specific pattern of oxytocin receptor expression might genetically predispose female cortex to respond to infant cues, which both males and females can also rapidly learn.