A new tissue-agnostic microfluidic device to model physiology and disease: the lattice platform.

To accurately phenocopy human biology , researchers have been reducing their dependence on standard, static two-dimensional (2D) cultures and instead are moving towards three-dimensional (3D) and/or multicellular culture techniques. While these culture innovations are becoming more commonplace, there is a growing body of research that illustrates the benefits and even necessity of recapitulating the dynamic flow of nutrients, gas, waste exchange and tissue interactions that occur . However, cost and engineering complexity are two main factors that hinder the adoption of these technologies and incorporation into standard laboratory workflows.

Exposure of human fallopian tube epithelium to elevated testosterone results in alteration of cilia gene expression and beating.

Study Question: How does exposure to a testosterone rich environment affect the function and gene expression of human fallopian tube epithelium (hFTE)?

Summary Answer: Elevated testosterone level alters several gene transcripts that regulate cilia expression and negatively impacts the rate of cilia beating.

What Is Known Already: The presence of estrogen in the follicular phase of the menstrual cycle increases the human fallopian tube ciliary beating frequency. The luteal phase, triggered by ovulation and increasing progesterone, is marked by a decrease in ciliary beating.

Distinct subtypes of polycystic ovary syndrome with novel genetic associations: An unsupervised, phenotypic clustering analysis.

Background: Polycystic ovary syndrome (PCOS) is a common, complex genetic disorder affecting up to 15% of reproductive-age women worldwide, depending on the diagnostic criteria applied. These diagnostic criteria are based on expert opinion and have been the subject of considerable controversy. The phenotypic variation observed in PCOS is suggestive of an underlying genetic heterogeneity, but a recent meta-analysis of European ancestry PCOS cases found that the genetic architecture of PCOS defined by different diagnostic criteria was generally similar, suggesting that the criteria do not identify biologically distinct disease subtypes.

Publisher Correction: Genome-wide association of polycystic ovary syndrome implicates alterations in gonadotropin secretion in European ancestry populations.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

A Polygenic and Phenotypic Risk Prediction for Polycystic Ovary Syndrome Evaluated by Phenome-Wide Association Studies.

Context: As many as 75% of patients with polycystic ovary syndrome (PCOS) are estimated to be unidentified in clinical practice.

Objective: Utilizing polygenic risk prediction, we aim to identify the phenome-wide comorbidity patterns characteristic of PCOS to improve accurate diagnosis and preventive treatment.

Design, Patients, And Methods: Leveraging the electronic health records (EHRs) of 124 852 individuals, we developed a PCOS risk prediction algorithm by combining polygenic risk scores (PRS) with PCOS component phenotypes into a polygenic and phenotypic risk score (PPRS).

Correction: Large-scale genome-wide meta-analysis of polycystic ovary syndrome suggests shared genetic architecture for different diagnosis criteria.

[This corrects the article DOI: 10.1371/journal.pgen.

Hyperandrogenemia is Common in Asymptomatic Women and is Associated with Increased Metabolic Risk.

Objective: Women with metabolic syndrome (MetS) have higher endogenous testosterone (T) levels than unaffected women. This study investigated whether hyperandrogenemia (HA) was a marker for increased cardiometabolic risk in reproductively normal premenopausal women.

Methods: Reproductive hormones and metabolic parameters were assessed in 198 women with regular menses and no clinical hyperandrogenism (eumenorrheic [EM]).

Scaffold-Free Endometrial Organoids Respond to Excess Androgens Associated With Polycystic Ovarian Syndrome.

Context: Polycystic ovary syndrome (PCOS) is a prevalent disorder in reproductive aged women associated with a number of endocrine and metabolic complications, including increased risk of endometrial cancer.

Objective: To study the effect of the characteristic increased androgen levels in PCOS on the endometrium, a novel scaffold-free multicellular endometrial organoid was established.

Design: Human endometrial organoids were constructed using primary endometrial epithelial and stromal cells from endometrial tissues.

Functional Genetic Variation in the Anti-Müllerian Hormone Pathway in Women With Polycystic Ovary Syndrome.

Context: Polycystic ovary syndrome (PCOS) is a highly heritable, common endocrine disorder characterized by hyperandrogenism, irregular menses, and polycystic ovaries. PCOS is often accompanied by elevated levels of anti-Müllerian hormone (AMH). AMH inhibits follicle maturation.

Large-scale genome-wide meta-analysis of polycystic ovary syndrome suggests shared genetic architecture for different diagnosis criteria.

Polycystic ovary syndrome (PCOS) is a disorder characterized by hyperandrogenism, ovulatory dysfunction and polycystic ovarian morphology. Affected women frequently have metabolic disturbances including insulin resistance and dysregulation of glucose homeostasis. PCOS is diagnosed with two different sets of diagnostic criteria, resulting in a phenotypic spectrum of PCOS cases.

Genome-wide association of polycystic ovary syndrome implicates alterations in gonadotropin secretion in European ancestry populations.

Polycystic ovary syndrome (PCOS) is a common, highly heritable complex disorder of unknown aetiology characterized by hyperandrogenism, chronic anovulation and defects in glucose homeostasis. Increased luteinizing hormone relative to follicle-stimulating hormone secretion, insulin resistance and developmental exposure to androgens are hypothesized to play a causal role in PCOS. Here we map common genetic susceptibility loci in European ancestry women for the National Institutes of Health PCOS phenotype, which confers the highest risk for metabolic morbidities, as well as reproductive hormone levels.

A retrospective, cross-sectional study reveals that women with CRSwNP have more severe disease than men.

Up to 50% of patients with chronic rhinosinusitis (CRS) have comorbid asthma, and we have reported that a subset of CRS patients who have nasal polyps (CRSwNP) have elevated autoantigen-specific antibodies within their nasal polyps (NP). While increases in the prevalence and/or severity of both asthma and autoimmunity in women are well characterized, it is not known whether CRSwNP is more severe or frequent in women than men. We sought to determine whether CRSwNP demonstrated sex-specific differences in frequency and/or severity.

Genetic risk score for prediction of newborn adiposity and large-for-gestational-age birth.

Context: Macrosomic infants are at increased risk for adverse metabolic outcomes. Improving prediction of large-for-gestational-age (LGA) birth may help prevent these outcomes.

Objective: This study sought to determine whether genes associated with obesity-related traits in adults are associated with newborn size, and whether a genetic risk score (GRS) predicts LGA birth.

Parent-of-origin effects on glucose homeostasis in polycystic ovary syndrome.

Context: Polycystic ovary syndrome (PCOS) is a highly heritable complex trait. Parents of affected women have reproductive and metabolic phenotypes.

Objective: We tested the hypothesis that there are parental effects on the heritability of fasting dysglycemia in women with PCOS.

The inflammatory gene pathway is not a major contributor to polycystic ovary snydrome.

Context: Although inflammation is clearly associated with obesity, diabetes, and insulin resistance, the role of chronic inflammation in the etiology of polycystic ovary syndrome (PCOS) is unclear.

Objective: To determine whether chronic inflammation plays a causal role in the etiology of PCOS, we tested for an association between PCOS and genetic markers mapping to 80 members of the inflammatory pathway.

Design: This was a case-control association study.

Identification of HKDC1 and BACE2 as genes influencing glycemic traits during pregnancy through genome-wide association studies.

Maternal metabolism during pregnancy impacts the developing fetus, affecting offspring birth weight and adiposity. This has important implications for metabolic health later in life (e.g.

The role of TGF-β in polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is a common endocrine disorder characterized by chronic oligoanovulation and hyperandrogenism and associated with insulin resistance, type 2 diabetes, and cardiovascular risk. In recent years, genetic studies have linked PCOS to a dinucleotide marker D19S884 in the fibrillin 3 gene. Fibrillins make up the major component of microfibrils in the extracellular matrix (ECM) and interact with molecules in the ECM to regulate transforming growth factor β (TGF-β) signaling.

The chromosome 3q25 genomic region is associated with measures of adiposity in newborns in a multi-ethnic genome-wide association study.

Newborns characterized as large and small for gestational age are at risk for increased mortality and morbidity during the first year of life as well as for obesity and dysglycemia as children and adults. The intrauterine environment and fetal genes contribute to the fetal size at birth. To define the genetic architecture underlying the newborn size, we performed a genome-wide association study (GWAS) in 4281 newborns in four ethnic groups from the Hyperglycemia and Adverse Pregnancy Outcome Study.

Accumulation of cadmium in insulin-producing β cells.

Evidence suggests that chronic low level cadmium exposure impairs the function of insulin-producing β cells and may be associated with type-2 diabetes mellitus. Herein, we describe the cadmium content in primary human islets and define the uptake kinetics and effects of environmentally relevant cadmium concentrations in cultured β cells. The average cadmium content in islets from 10 non-diabetic human subjects was 29 ± 7 nmol/g protein (range 7 to 72 nmol/g protein).