Androgen signalling in the ovaries and endometrium.

Currently, our understanding of hormonal regulation within the female reproductive system is largely based on our knowledge of estrogen and progesterone signalling. However, while the important functions of androgens in male physiology are well known, it is also recognized that androgens play critical roles in the female reproductive system. Further, androgen signalling is altered in a variety of gynaecological conditions, including endometriosis and polycystic ovary syndrome, indicative of regulatory roles in endometrial and ovarian function. Co-regulatory mechanisms exist between different androgens, estrogens, and progesterone, resulting in a complex network of steroid hormone interactions. Evidence from animal knockout studies, in vitro experiments, and human data indicate that androgen receptor expression is cell-specific and menstrual cycle stage-dependent, with important regulatory roles in the menstrual cycle, endometrial biology, and follicular development in the ovaries. This review will discuss the expression and co-regulatory interactions of androgen receptors, highlighting the complexity of the androgen signalling pathway in the endometrium and ovaries, and the synthesis of androgens from additional alternative pathways previously disregarded as male-specific. Moreover, it will illustrate the challenges faced when studying androgens in female biology, and the need for a more in-depth, integrative view of androgen metabolism and signalling in the female reproductive system.

Systematic review of dog bite prevention strategies.

BACKGROUND: The prevention of dog bites is an increasingly important public health topic, as the incidence of serious injury continues to rise. OBJECTIVES: To evaluate the effectiveness of interventions to prevent dog bites and aggression. METHODS: Online databases were searched (PubMed, Cochrane Library, Embase and Google Scholar), using the search terms: dog/s, canine, canis, kuri, bite/s, bitten, aggression, attack, death, fatal, mortality, injury/ies, prevention, intervention, for studies between 1960 and 2021. All study designs were considered. Outcomes of interest were the incidence of dog bites or dog aggression. Non-English studies, and those without full-text access were excluded. RESULTS: Forty-three studies met the review criteria, including 15 observational and 27 interventional studies. Fifteen studies investigating dog-control legislation, including leash laws, stray dog control and infringements indicated this can reduce dog bite rates. Breed-specific legislation had less of an effect. Six studies investigating sterilisation, showed while this may reduce dog bites through a reduction in the dog population, the effect on dog aggression was unclear. An alcohol reduction programme showed a significant reduction in dog bite rates in one study. Seven studies assessing educational approaches found that intensive adult-directed education may be effective, with one study showing child-directed education was not effective. Eight studies on dog training (two police-dog related), and six evaluating dog medication or diet were generally low quality and inconclusive. CONCLUSIONS: Multiple strategies including effective engagement with indigenous communities and organisations will be required to reduce dog-bites and other incidents involving dog aggression. This review provides some evidence that legislated dog control strategies reduce dog bite rates. Available evidence suggests greater restrictions should be made for all dogs, rather than based on breed alone. Due to a burden of child injury, protection of children should be a focus of legislation and further investigations. Prevention strategies in children require redirection away from a focus on child-directed education and future research should investigate the effectiveness of engineering barriers and reporting strategies.

Cytokines and pregnancy: Potential regulation by histone deacetylases.

Cytokines are important regulators of pregnancy and parturition. Aberrant expression of proinflammatory cytokines during pregnancy contributes towards preterm labor, pre-eclampsia, and gestational diabetes mellitus. The regulation of cytokine expression in human cells is highly complex, involving interactions between environment, transcription factors, and feedback mechanisms. Recent developments in epigenetic research have made tremendous advancements in exploring histone modifications as a key epigenetic regulator of cytokine expression and the effect of their signaling molecules on various organ systems in the human body. Histone acetylation and subsequent deacetylation by histone deacetylases (HDACs) are major epigenetic regulators of protein expression in the human body. The expression of various proinflammatory cytokines, their role in normal and abnormal pregnancy, and their epigenetic regulation via HDACs will be discussed in this review.

Histone acetylation and the role of histone deacetylases in normal cyclic endometrium.

Histone acetylation is a critical epigenetic modification that changes chromatin architecture and regulates gene expression by opening or closing the chromatin structure. It plays an essential role in cell cycle progression and differentiation. The human endometrium goes through cycles of regeneration, proliferation, differentiation, and degradation each month; each phase requiring strict epigenetic regulation for the proper functioning of the endometrium. Aberrant histone acetylation and alterations in levels of two acetylation modulators - histone acetylases (HATs) and histone deacetylases (HDACs) - have been associated with endometrial pathologies such as endometrial cancer, implantation failures, and endometriosis. Thus, histone acetylation is likely to have an essential role in the regulation of endometrial remodelling throughout the menstrual cycle.