Recent reports have described an intricate interplay among diverse RNA species, including protein-coding messenger RNAs and non-coding RNAs such as long non-coding RNAs, pseudogenes and circular RNAs. These RNA transcripts act as competing endogenous RNAs (ceRNAs) or natural microRNA sponges — they communicate with and co-regulate each other by competing for binding to shared microRNAs, a family of small non-coding RNAs that are important post-transcriptional regulators of gene expression. Understanding this novel RNA crosstalk will lead to significant insight into gene regulatory networks and have implications in human development and disease.

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The multilayered complexity of ceRNA crosstalk and competition

Genomes of multicellular organisms are characterized by the pervasive expression of different types of non-coding RNAs (ncRNAs). Long ncRNAs (lncRNAs) belong to a novel heterogeneous class of ncRNAs that includes thousands of different species. lncRNAs have crucial roles in gene expression control during both developmental and differentiation processes, and the number of lncRNA species increases in genomes of developmentally complex organisms, which highlights the importance of RNA-based levels of control in the evolution of multicellular organisms. In this Review, we describe the function of lncRNAs in developmental processes, such as in dosage compensation, genomic imprinting, cell differentiation and organogenesis, with a particular emphasis on mammalian development.

Long non-coding RNAs: new players in cell differentiation and development

Long Noncoding RNAs in Cancer Pathways

Thousands of unique non-coding RNA (ncRNA) sequences exist within cells. Work from the past decade has altered our perception of ncRNAs from 'junk' transcriptional products to functional regulatory molecules that mediate cellular processes including chromatin remodelling, transcription, post-transcriptional modifications and signal transduction. The networks in which ncRNAs engage can influence numerous molecular targets to drive specific cell biological responses and fates. Consequently, ncRNAs act as key regulators of physiological programmes in developmental and disease contexts. Particularly relevant in cancer, ncRNAs have been identified as oncogenic drivers and tumour suppressors in every major cancer type. Thus, a deeper understanding of the complex networks of interactions that ncRNAs coordinate would provide a unique opportunity to design better therapeutic interventions.

Non-coding RNA networks in cancer.

The Role of Non-coding RNAs in Oncology

The imprinted H19 lncRNA antagonizes let-7 microRNAs.

Importance In the US, approximately 12.7% of reproductive age women seek treatment for infertility each year. This review summarizes current evidence regarding diagnosis and treatment of infertility. Observations Infertility is defined as the failure to achieve pregnancy after 12 months of regular unprotected sexual intercourse. Approximately 85% of infertile couples have an identifiable cause. The most common causes of infertility are ovulatory dysfunction, male factor infertility, and tubal disease. The remaining 15% of infertile couples have “unexplained infertility.” Lifestyle and environmental factors, such as smoking and obesity, can adversely affect fertility. Ovulatory disorders account for approximately 25% of infertility diagnoses; 70% of women with anovulation have polycystic ovary syndrome. Infertility can also be a marker of an underlying chronic disease associated with infertility. Clomiphene citrate, aromatase inhibitors such as letrozole, and gonadotropins are used to induce ovulation or for ovarian stimulation during in vitro fertilization (IVF) cycles. Adverse effects of gonadotropins include multiple pregnancy (up to 36% of cycles, depending on specific therapy) and ovarian hyperstimulation syndrome (1%-5% of cycles), consisting of ascites, electrolyte imbalance, and hypercoagulability. For individuals presenting with anovulation, ovulation induction with timed intercourse is often the appropriate initial treatment choice. For couples with unexplained infertility, endometriosis, or mild male factor infertility, an initial 3 to 4 cycles of ovarian stimulation may be pursued; IVF should be considered if these approaches do not result in pregnancy. Because female fecundity declines with age, this factor should guide decision-making. Immediate IVF may be considered as a first-line treatment strategy in women older than 38 to 40 years. IVF is also indicated in cases of severe male factor infertility or untreated bilateral tubal factor. Conclusions and Relevance Approximately 1 in 8 women aged 15 to 49 years receive infertility services. Although success rates vary by age and diagnosis, accurate diagnosis and effective therapy along with shared decision-making can facilitate achievement of fertility goals in many couples treated for infertility.

https://jamanetwork.com/journals/jama/articlepdf/2781637/jama_carson_2021_rv_210009_1625172026.74764.pdf

Diagnosis and Management of Infertility: A Review.

Objective: Atherosclerosis is a complex process characterized by an increase in vascular wall thickness owing to the accumulation of cells and extracellular matrix between the endothelium and the smooth muscle cell wall. There is evidence thatfemales are at lower risk ofdeveloping cardiovascular disease (CVD) as compared to males. This has led to an interest in examining the contribution of genetic background and sex hormones to the development of CVD. The objective of this review is to provide an overview of factors, including those related to gender, that influence CVD. Methods: Evidence analysis from PubMed and individual searches concerning biochemical and endocrine influences and gender differences, which affect the origin and development of CVD. Results: Although still controversial, evidence suggests that hormones including estradiol and androgens are responsible for subtle cardiovascular changes long before the development of overt atherosclerosis. Conclusion: Exposure to sex hormones throughout an individualis lifespan modulates many endocrine factors involved in atherosclerosis.

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Gender differences in cardiovascular disease: hormonal and biochemical influences.

Purpose of review Coronary heart disease (CHD) is the leading cause of death in the aging female population in the developed world. Ovarian endocrinology plays an important role in modulating a woman's CHD risk. We herein present an overview of our current understanding of CHD risk profile in the context of ovarian physiology and senescence. Recent findings Endogenous ovarian estrogen has long been recognized to offer cardiac benefit and vascular protection against atherosclerosis. Existing data, however, do not allow for an extrapolation of the recognized cardioprotective implications of the reproductive-age endogenous estrogenic milieu to the use of exogenous estrogen in postmenopausal women. Ongoing efforts are targeting the concept that when reintroduced proximate to onset of ovarian senescence, exogenous estrogen may retard the process of atherogenesis. Until this hypothesis is substantiated, cardioprotection must not be an indication for initiating hormone therapy in menopausal women. Summary Ovarian hormones modulate the processes of atherosclerosis and the mechanisms underlying CHD. The female reproductive hormones offer a cardioprotective milieu that is rapidly attenuated with the cessation of ovarian function (be it following natural menopause or after medical or surgical ovarian extirpation). The role of exogenous hormone therapy, and the nuances of timing and duration of exposure, are still being elucidated.

Cardiovascular disease and ovarian function.

https://www.fertstert.org/article/S0015-0282(15)00165-X/pdf

Amanda N. Kallen

Papers

The imprinted H19 lncRNA antagonizes let-7 microRNAs.

Diagnosis and Management of Infertility: A Review.

Gender differences in cardiovascular disease: hormonal and biochemical influences.

Cardiovascular disease and ovarian function.

Poor ovarian response in women undergoing in vitro fertilization is associated with altered microRNA expression in cumulus cells