Volume 2, Issue 5 - Special Issue on Reproductive Health

The occurrence and mechanisms of developmental adult diseases have gradually attracted attention in recent years. Exposure of gametes and embryos to adverse environments, especially during plastic development, can alter the expression of certain tissue-specific genes, leading to increased susceptibility to certain diseases in adulthood, such as diabetes, cardiovascular disease, neuropsychiatric, and reproductive system diseases, etc. The occurrence of chronic disease in adulthood is partly due to genetic factors, and the remaining risk is partly due to environmental-dependent epigenetic information alteration, including DNA methylation, histone modifications, and noncoding RNAs. Changes in this epigenetic information potentially damage our health, which has also been supported by numerous epidemiological and animal studies in recent years. Environmental factors functionally affect embryo development through epimutation, transmitting diseases to offspring and even later generations. This review mainly elaborated on the concept of developmental origins of adult diseases, and revealed the epigenetic mechanisms underlying these events, discussed the theoretical basis for the prevention and treatment of related diseases.

Advancements in genome editing enable permanent changes of DNA sequences in a site-specific manner, providing promising approaches for treating human genetic disorders caused by gene mutations. Recently, genome editing has been applied and achieved significant progress in treating inherited genetic disorders that remain incurable by conventional therapy. Here, we present a review of various programmable genome editing systems with their principles, advantages, and limitations. We introduce their recent applications for treating inherited diseases in the clinic, including sickle cell disease (SCD), β-thalassemia, Leber congenital amaurosis (LCA), heterozygous familial hypercholesterolemia (HeFH), etc. We also discuss the paradigm of ex vivo and in vivo editing and highlight the promise of somatic editing and the challenge of germline editing. Finally, we propose future directions in delivery, cutting, and repairing to improve the scope of clinical applications.

Pregnant women are often complicated with diseases that require treatment with medication. Most drugs administered to pregnant women are off-label without the necessary dose, efficacy, and safety information. Knowledge concerning drug transfer across the placental barrier is essential for understanding fetal drug exposure and hence drug safety and efficacy to the fetus. Transporters expressed in the placenta, including adenosine triphosphate (ATP)-binding cassette efflux transporters and solute carrier uptake transporters, play important roles in determining drug transfer across the placental barrier, leading to fetal exposure to the drugs. In this review, we provide an update on placental drug transport, including in vitro cell/tissue, ex vivo human placenta perfusion, and in vivo animal studies that can be used to determine the expression and function of drug transporters in the placenta as well as placental drug transfer and fetal drug exposure. We also describe how the knowledge of placental drug transfer through passive diffusion or active transport can be combined with physiologically based pharmacokinetic modeling and simulation to predict systemic fetal drug exposure. Finally, we highlight knowledge gaps in studying placental drug transport and predicting fetal drug exposure and discuss future research directions to fill these gaps.

The organoid field has been developing rapidly during the last decade. Organoids for human pre-, peri- and post-implantation development have opened an avenue to study these biological processes in vitro , which have been hampered by lack of accessible research models for long term. The technologies of four fields, single cell omics sequencing, genome editing and lineage tracing, microfluidics and tissue engineering, have fueled the rapid development of the organoid field. In this review, we will discuss the organoid research on human early development as well as future directions of the organoid field combining with other powerful technologies.

Dietary interventions include the change of dietary styles, such as fasting and dietary or nutrient restrictions; or the addition of plant-derived compounds (such as polyphenols known as curcumin, resveratrol, or anthocyanin, or other nutraceuticals) into the diet. During the past a few decades, large number of studies have demonstrated therapeutic activities of these dietary interventions on metabolic and other diseases in human subjects or various animal models. Mechanisms underlying those versatile therapeutic activities, however, remain largely unclear. Interestingly, recent studies have shown that fibroblast growth factor 21 (FGF21), a liver-derived hormone or hepatokine, mediates metabolic beneficial effects of certain dietary polyphenols as well as protein restriction. Here I have briefly summarized functions of FGF21, highlighted related dietary interventions, and presented literature discussions on role of FGF21 in mediating function of dietary polyphenol intervention and protein restriction. This is followed by presenting my perspective view, with the involvement of gut microbiota. It is anticipated that further breakthroughs in this field in the near future will facilitate conceptual merge of classical medicine and modern medicine.

Gamma-aminobutyric acid (GABAergic) neuron, as one of important cell types in synaptic transmission, has been widely involved in central nervous system (CNS) regulation of organismal physiologies including cognition, emotion, arousal and reward. However, upon their distribution in various brain regions, effects of GABAergic neurons in the brain are very diverse. In current report, we will present an overview of the role of GABAergic mediated inhibitory neurocircuitry in the hypothalamus, underlying mechanism of feeding and sleep homeostasis as well as the characteristics of latest transcriptome profile in order to call attention to the GABAergic system as potentially a promising pharmaceutical intervention or a deep brain stimulation target in eating and sleep disorders.