Phenotypes Associated With Polycystic Ovary Syndrome Risk Variants.

Context: Polycystic ovary syndrome (PCOS) affects 10% of women of reproductive age. The genetic architecture of the disease is emerging, but there is little data exploring the effect of genetic risk on clinical presentation.

Objective: We hypothesized that genetic risk loci would influence measurable phenotypic traits.

Breast Cancer is Increased in Women with Primary Ovarian Insufficiency.

Context: DNA damage/repair gene variants are associated with both primary ovarian insufficiency (POI) and cancer risk.

Objective: We hypothesized that a subset of women with POI and family members would have increased risk for cancer.

Design: Case-control population-based study using records from 1995-2022.

Heterozygous Stop Gain Mice Replicate the Primary Ovarian Insufficiency Phenotype in Women.

We created the c.1286C>G stop-gain mutation found in a family with primary ovarian insufficiency (POI) at age 30 years. The C57/Bl6 transgenic mouse model contained a floxed exon 10-19 cassette with a conditional knock-in cassette containing the c.

Disuse-induced muscle fibrosis, cellular senescence, and senescence-associated secretory phenotype in older adults are alleviated during re-ambulation with metformin pre-treatment.

Muscle inflammation and fibrosis underlie disuse-related complications and may contribute to impaired muscle recovery in aging. Cellular senescence is an emerging link between inflammation, extracellular matrix (ECM) remodeling and poor muscle recovery after disuse. In rodents, metformin has been shown to prevent cellular senescence/senescent associated secretory phenotype (SASP), inflammation, and fibrosis making it a potentially practical therapeutic solution.

DIS3 Variants are Associated With Primary Ovarian Insufficiency: Importance of Transcription/Translation in Oogenesis.

Context: A genetic etiology accounts for the majority of unexplained primary ovarian insufficiency (POI).

Objective: We hypothesized a genetic cause of POI for a sister pair with primary amenorrhea.

Design: The study was an observational study.

Primary ovarian insufficiency has strong familiality: results of a multigenerational genealogical study.

Objective: To determine the familiality of primary ovarian insufficiency (POI) at population level through examination of multigenerational genealogical information linked to electronic medical records.

Design: Case-control study.

Setting: Not applicable.

The Use of Ceramides to Predict Metabolic Response to Metformin in Women With PCOS.

Context: Polycystic ovarian syndrome (PCOS) is a complex disorder in which metabolic abnormalities are associated with reproductive dysfunction. Women with PCOS have increased ceramide concentrations. Previous studies demonstrated that treating metabolic abnormalities of PCOS with metformin improved glucose effectiveness after 12 weeks.

Health-related quality of life in women with primary ovarian insufficiency: a scoping review of the literature and implications for targeted interventions.

Study Question: What is known about health-related quality of life (HR-QoL) in women with idiopathic primary ovarian insufficiency (POI)?

Summary Answer: Women with POI have a range of unmet psychosocial needs relating to three interrelated themes: 'diagnostic odyssey', 'isolation and stigma' and impaired 'ego integrity'.

What Is Known Already: Prior studies have reported increased depressive symptoms, diminished sexual function and altered body image/self-concept in women with POI.

Study Design, Size, Duration: A systematic scoping review (11 databases) on HR-QoL in POI including published quantitative, qualitative and mixed-methods studies as well as unpublished gray literature (i.

Causal and Candidate Gene Variants in a Large Cohort of Women With Primary Ovarian Insufficiency.

Context: A genetic etiology likely accounts for the majority of unexplained primary ovarian insufficiency (POI).

Objective: We hypothesized that heterozygous rare variants and variants in enhanced categories are associated with POI.

Design: The study was an observational study.

Practical Approach to Hyperandrogenism in Women.

The approach to hyperandrogenism in women varies depending on the woman's age and severity of symptoms. Once tumorous hyperandrogenism is excluded, the most common cause is PCOS. Hirsutism is the most common presenting symptom.

Shared genetics between nonobstructive azoospermia and primary ovarian insufficiency.

Objective: Primary ovarian insufficiency (POI) and Non-obstructive azoospermia (NOA) both represent disease states of early, and often complete, failure of gametogenesis. Because oogenesis and spermatogenesis share the same conserved steps in meiosis I, it is possible that inherited defects in meiosis I could lead to shared causes of both POI and NOA. Currently, known genes that contribute to both POI and NOA are limited.

Identifying susceptibility genes for primary ovarian insufficiency on the high-risk genetic background of a fragile X premutation.

Objective: To identify modifying genes that explains the risk of fragile X-associated primary ovarian insufficiency (FXPOI).

Design: Gene-based, case/control association study, followed by a functional screen of highly ranked genes using a Drosophila model.

Setting: Participants were recruited from academic and clinical settings.

Single nucleus multi-omics regulatory landscape of the murine pituitary.

To provide a multi-omics resource and investigate transcriptional regulatory mechanisms, we profile the transcriptome, chromatin accessibility, and methylation status of over 70,000 single nuclei (sn) from adult mouse pituitaries. Paired snRNAseq and snATACseq datasets from individual animals highlight a continuum between developmental epigenetically-encoded cell types and transcriptionally-determined transient cell states. Co-accessibility analysis-based identification of a putative Fshb cis-regulatory domain that overlaps the fertility-linked rs11031006 human polymorphism, followed by experimental validation illustrate the use of this resource for hypothesis generation.

PRL Mutation Causing Alactogenesis: Insights Into Prolactin Structure and Function Relationships.

Context: Isolated prolactin deficiency is a rare disorder manifesting as absence of puerperal lactation. We identified a 2-generation family with 3 women experiencing alactogenesis.

Objective: We hypothesized a heterozygous genetic mutation.

Genetics of Polycystic Ovary Syndrome: What is New?

Polycystic ovary syndrome (PCOS) is a complex genetic disorder with many genetic loci contributing small risk. Large genome-wide association studies identified 21 genetic risk loci for PCOS in European and Han Chinese women. The genetic architecture is similar across PCOS diagnostic categories.

Increased Burden of Rare Sequence Variants in GnRH-Associated Genes in Women With Hypothalamic Amenorrhea.

Context: Functional hypothalamic amenorrhea (HA) is a common, acquired form of hypogonadotropic hypogonadism that occurs in the setting of energy deficits and/or stress. Variability in individual susceptibility to these stressors, HA heritability, and previous identification of several rare sequence variants (RSVs) in genes associated with the rare disorder, isolated hypogonadotropic hypogonadism (IHH), in individuals with HA suggest a possible genetic contribution to HA susceptibility.

Objective: We sought to determine whether the burden of RSVs in IHH-related genes is greater in women with HA than controls.

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.

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.

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.

Healthy Post-Menarchal Adolescent Girls Demonstrate Multi-Level Reproductive Axis Immaturity.

Context: Menstrual irregularity after menarche has been attributed to immature estrogen positive feedback activity (E+FB) but data are conflicting.

Objective: To determine the hypothalamic-pituitary-ovarian contributions to menstrual irregularity in adolescents.

Methods: Twenty-three healthy girls [aged 12.

Mutations Are Associated With Primary Ovarian Insufficiency in Women.

Context: Primary ovarian insufficiency (POI) results from a premature loss of oocytes, causing infertility and early menopause. The etiology of POI remains unknown in a majority of cases.

Objective: To identify candidate genes in families affected by POI.