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Endocrine-disrupting chemicals (EDCs) adversely affect human health. Our objective was to determine the association of EDC exposure with earlier age of menopause. Cross-sectional survey using National Health and Nutrition Examination Survey (NHANES) data from 1999 to 2008 (n = 31,575 females). Eligible participants included: menopausal women >30 years of age; not currently pregnant, breastfeeding, using hormonal contraception; no history of bilateral oophorectomy or hysterectomy. Exposures, defined by serum lipid and urine creatinine-adjusted measures of EDCs, data were analyzed: > 90th percentile of the EDC distribution among all women, log-transformed EDC level, and decile of EDC level. Multi linear regression models considered complex survey design characteristics and adjusted for age, race/ethnicity, smoking, body mass index. EDCs were stratified into long (>1 year), short, and unknown half-lives; principle analyses were performed on those with long half-lives as well as phthalates, known reproductive toxicants. Secondary analysis determined whether the odds of being menopausal increased with EDC exposure among women aged 45-55 years. This analysis examined 111 EDCs and focused on known reproductive toxicants or chemicals with half-lives >1 year. Women with high levels of β-hexachlorocyclohexane, mirex, p,p'-DDE, 1,2,3,4,6,7,8-heptachlorodibenzofuran, mono-(2-ethyl-5-hydroxyhexyl) and mono-(2-ethyl-5-oxohexyl) phthalate, polychlorinated biphenyl congeners -70, -99, -105, -118, -138, -153, -156, -170, and -183 had mean ages of menopause 1.9 to 3.8 years earlier than women with lower levels of these chemicals. EDC-exposed women were up to 6 times more likely to be menopausal than non-exposed women. This study of a representative sample of US women documents an association between EDCs and earlier age at menopause. We identified 15 EDCs that warrant closer evaluation because of their persistence and potential detrimental effects on ovarian function. Earlier menopause can alter the quantity and quality of a woman's life and has profound implications for fertility, human reproduction, and our global society.

Fertility is important to women and men with cancer. While options for fertility preservation (FP) are available, knowledge regarding the medical application of FP is lacking. Therefore we examined FP practices for cancer patients among reproductive endocrinologists (REs). A 36 item survey was sent to board-certified REs. 98% of respondents reported counseling women with cancer about FP options. Oocyte and embryo cryopreservation were universally offered by these providers, but variability was noted in reported management of these cases-particularly for women with breast cancer. 86% of the respondents reported using letrozole during controlled ovarian stimulation (COS) in patients with estrogen receptor positive (ER+) breast cancer to minimize patient exposure to estrogen. 49% of respondents who reported using letrozole in COS for patients with ER+ breast cancer reported that they would also use letrozole in COS for women with ER negative breast cancer. Variability was also noted in the management of FP for men with cancer. 83% of participants reported counseling men about sperm banking with 22% recommending against banking for men previously exposed to chemotherapy. Overall, 79% of respondents reported knowledge of American Society for Clinical Oncology FP guidelines-knowledge that was associated with providers offering gonadal tissue cryopreservation (RR 1.82, 95% CI 1.14-2.90). These findings demonstrate that RE management of FP in cancer patients varies. Although some variability may be dictated by local resources, standardization of FP practices and communication with treating oncologists may help ensure consistent recommendations and outcomes for patients seeking FP.

Presenting the most current and relevant information on the diagnosis and management of primary ovarian insufficiency, also known as premature ovarian failure (POI/POF), this book presents two equally important voices.

Abstract 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. Subjects were recruited at an academic institution. Subjects Subjects were sisters with primary amenorrhea caused by POI and their parents. Additional subjects included women with POI analyzed previously (n = 291). Controls were recruited for health in old age or were from the 1000 Genomes Project (total n = 233). Intervention We performed whole exome sequencing, and data were analyzed using the Pedigree Variant Annotation, Analysis and Search Tool, which identifies genes harboring pathogenic variants in families. We performed functional studies in a Drosophila melanogaster model. Main Outcome Genes with rare pathogenic variants were identified. Results The sisters carried compound heterozygous variants in DIS3. The sisters did not carry additional rare variants that were absent in publicly available datasets. DIS3 knockdown in the ovary of D. melanogaster resulted in lack of oocyte production and severe infertility. Conclusions Compound heterozygous variants in highly conserved amino acids in DIS3 and failure of oocyte production in a functional model suggest that mutations in DIS3 cause POI. DIS3 is a 3′ to 5′ exoribonuclease that is the catalytic subunit of the exosome involved in RNA degradation and metabolism in the nucleus. The findings provide further evidence that mutations in genes important for transcription and translation are associated with POI.

Objective Endocrine-disrupting chemicals (EDCs) adversely affect human health. Our objective was to determine the association of EDC exposure with earlier age of menopause. Methods Cross-sectional survey using National Health and Nutrition Examination Survey (NHANES) data from 1999 to 2008 (n = 31,575 females). Eligible participants included: menopausal women >30 years of age; not currently pregnant, breastfeeding, using hormonal contraception; no history of bilateral oophorectomy or hysterectomy. Exposures, defined by serum lipid and urine creatinine-adjusted measures of EDCs, data were analyzed: > 90th percentile of the EDC distribution among all women, log-transformed EDC level, and decile of EDC level. Multi linear regression models considered complex survey design characteristics and adjusted for age, race/ethnicity, smoking, body mass index. EDCs were stratified into long (>1 year), short, and unknown half-lives; principle analyses were performed on those with long half-lives as well as phthalates, known reproductive toxicants. Secondary analysis determined whether the odds of being menopausal increased with EDC exposure among women aged 45-55 years. Findings This analysis examined 111 EDCs and focused on known reproductive toxicants or chemicals with half-lives >1 year. Women with high levels of beta -hexachlorocyclohexane, mirex, p,p'-DDE, 1,2,3,4,6,7,8-heptachlorodibenzofuran, mono-(2-ethyl-5-hydroxyhexyl) and mono-(2-ethyl-5-oxohexyl) phthalate, polychlorinated biphenyl congeners -70, -99, -105, -118, -138, -153, -156, -170, and -183 had mean ages of menopause 1.9 to 3.8 years earlier than women with lower levels of these chemicals. EDC-exposed women were up to 6 times more likely to be menopausal than non-exposed women. Conclusions This study of a representative sample of US women documents an association between EDCs and earlier age at menopause. We identified 15 EDCs that warrant closer evaluation because of their persistence and potential detrimental effects on ovarian function. Earlier menopause can alter the quantity and quality of a woman's life and has profound implications for fertility, human reproduction, and our global society.

The vast majority of POI cases throughout the world are spontaneous and idiopathic. Despite expansion of genetic testing, lowered cost, and increased awareness, 90 % of idiopathic, spontaneous POI has no known etiology. The genetics of POI is a growing body of literature and new candidate genes are discovered daily. This chapter presents genetic syndromes of POI and non-syndromic genetic etiologies and describes the unique nature of the X chromosome. If there is a genetic explanation for a woman’s POI, discovering that diagnosis is essential in formulating an individualized prognosis, estimating chance of pregnancy, and learning about future health implications.

Ovarian aging ultimately results in the cessation of reproductive function and is thought to occur as a result of oocyte depletion. The associated hormonal changes are well defined, and the serum measurements of several of these hormones have been utilized to predict ovarian reserve in women presenting with infertility. Obesity is associated with subfertility and may contribute to pathologic ovarian aging, although a mechanism has yet to be defined. The evaluation of obese women presenting with infertility is complicated by the effect of obesity on markers of ovarian reserve. Additional investigation into the relationship between obesity and ovarian aging is needed to further clarify the role of increased adiposity on infertility, improve the success of assisted reproductive technologies in this population, and better counsel these patients.

Phenylalanine is a vital component of proteins in all living organisms, and in plants is a precursor for thousands of additional metabolites. Animals are incapable of synthesizing phenylalanine and must primarily obtain it directly or indirectly from plants. Although plants can synthesize phenylalanine in plastids through arogenate, the contribution of an alternative pathway via phenylpyruvate, as occurs in most microbes, has not been demonstrated. Here we show that plants also utilize a microbial-like phenylpyruvate pathway to produce phenylalanine, and flux through this route is increased when the entry point to the arogenate pathway is limiting. Unexpectedly, we find the plant phenylpyruvate pathway utilizes a cytosolic aminotransferase that links the coordinated catabolism of tyrosine to serve as the amino donor, thus interconnecting the extra-plastidial metabolism of these amino acids. This discovery uncovers another level of complexity in the plant aromatic amino acid regulatory network, unveiling new targets for metabolic engineering. Plants primarily synthesize phenylalanine in plastids via arogenate. Here, Yoo et al . provide evidence that petunia flowers also employ an alternative microbial-like pathway to synthesize phenylalanine that is partially localized in the cytosol and interconnected with tyrosine catabolism.

Despite improvements in mortality rates over the past several decades, cardiovascular (CV) disease remains the leading cause of death for African-Americans (AAs). Innovative approaches through mobile health (mHealth) interventions have the potential to support lifestyle change for CV disease prevention among AAs. We aimed to translate a behavioral theory-informed, evidence-based, face-to-face health education program into an mHealth lifestyle intervention for AAs. We describe the design and development of a culturally relevant, CV health and wellness digital application (app) and pilot testing using a community-based participatory research (CBPR) approach with AA churches. This mixed methods study used a 4-phase iterative development process for intervention design with the AA community. Phase 1 included focus groups with AA community members and church partners (n = 23) to gain insight regarding potential app end user preferences. In Phase 2, the interdisciplinary research team synthesized Phase 1 input for preliminary app design and content development. Phase 3 consisted of a sequential 3-meeting series with church partners (n = 13) for iterative app prototyping (assessment, cultural tailoring, final review). Phase 4, a single group pilot study among AA church congregants (n = 50), assessed app acceptability, usability, and satisfaction. Phase 1 focus groups indicated general and health-related apps preferences: multifunctional, high-quality graphics/visuals, evidence-based, yet simple health information and social networking capability. Phase 2 integrated these preferences into the preliminary app prototype. Phase 3 feedback was used to refine the app prototype for pilot testing. Phase 4 pilot testing indicated high app acceptability, usability, and satisfaction. This study illustrates integration of formative and CBPR approaches to design a culturally relevant, mHealth lifestyle intervention to address CV health disparities among AAs. Given the positive app perceptions, our study supports the use of an iterative development process by others interested in implementing an mHealth lifestyle intervention for racial/ethnic minority communities. Clinicaltrials.gov NCT03084822.

Background Salmonids are one of the most intensely studied fish, in part due to their economic and environmental importance, and in part due to a recent whole genome duplication in the common ancestor of salmonids. This duplication greatly impacts species diversification, functional specialization, and adaptation. Extensive new genomic resources have recently become available for Atlantic salmon ( Salmo salar ), but documentation of allelic versus duplicate reference genes remains a major uncertainty in the complete characterization of its genome and its evolution. Results From existing expressed sequence tag (EST) resources and three new full-length cDNA libraries, 9,057 reference quality full-length gene insert clones were identified for Atlantic salmon. A further 1,365 reference full-length clones were annotated from 29,221 northern pike ( Esox lucius ) ESTs. Pairwise d N /d S comparisons within each of 408 sets of duplicated salmon genes using northern pike as a diploid out-group show asymmetric relaxation of selection on salmon duplicates. Conclusions 9,057 full-length reference genes were characterized in S. salar and can be used to identify alleles and gene family members. Comparisons of duplicated genes show that while purifying selection is the predominant force acting on both duplicates, consistent with retention of functionality in both copies, some relaxation of pressure on gene duplicates can be identified. In addition, there is evidence that evolution has acted asymmetrically on paralogs, allowing one of the pair to diverge at a faster rate.