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Biomarkers for assessing reproductive development and health: Part 1--Pubertal development.

ABSTRACT: The proposed National Children's Study has helped raise awareness of the issues related to children's health and the importance of monitoring the growth and development of children from preconception through adulthood. Many genetic predispositions can adversely impact the normal development process, and various environmental exposures have been linked to adverse reproductive health in rodent models and a small number of accidental human exposures. To monitor reproductive health and identify adverse effects at the earliest possible juncture, investigators must develop a network of biomarkers covering all stages and aspects of reproductive development and function. Biomarkers are biological indicators that can be measured repeatedly and are informative on one or more aspects of biological development or function. They can range from the anatomical level down to the molecular level and may provide information on the nature of an exposure, the effect of an exposure, or the susceptibility of individuals or populations to the toxic effects of an exposure. In theory, biomarkers can be used to monitor a wide variety of conditions and responses ranging from abnormal development to early indicators of late-onset disease. The main stumbling block with this theory has been finding appropriate biomarkers for particular conditions and exposures. Such biomarkers must be easily accessible, robust, and sensitive. Ideally, they will be expressed across a large section of the population, and can be monitored quickly, easily, conveniently, and with minimal cost. In this review, we discuss some of the current and emerging biomarkers of human pubertal development.

SUBMITTER: Rockett JC

PROVIDER: S-EPMC1241804 | biostudies-other | 2004 Jan

REPOSITORIES: biostudies-other

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Biomarkers for assessing reproductive development and health: Part 1--Pubertal development.

Rockett John C JC Lynch Courtney D CD Buck Germaine M GM

Environmental health perspectives 20040101 1

The proposed National Children's Study has helped raise awareness of the issues related to children's health and the importance of monitoring the growth and development of children from preconception through adulthood. Many genetic predispositions can adversely impact the normal development process, and various environmental exposures have been linked to adverse reproductive health in rodent models and a small number of accidental human exposures. To monitor reproductive health and identify adve ...[more]

PMID: 14698938

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Project description:BackgroundOver the past several decades, the age of pubertal onset in girls has shifted downward worldwide. As early pubertal onset is associated with increased risky behavior and psychological issues during adolescence and cardiometabolic disease and cancer in adulthood, this is an important public health concern. Exposure to endocrine disrupting chemicals during critical windows of in utero development may play a role in this trend. Our objective was to investigate trimester-specific phthalate and BPA exposure in relation to pubertal development among girls in the Early Life Exposure in Mexico to Environmental Toxicants (ELEMENT) birth cohort.MethodsWe measured maternal urinary phthalate metabolites and BPA in samples collected during the first, second, and third trimesters of pregnancy. To assess reproductive development among their female children, we measured serum testosterone, estradiol, dehydroepiandrosterone sulfate (DHEA-S), inhibin B, and sex hormone-binding globulin (SHBG), and assessed sexual maturation, including Tanner staging for breast and pubic hair development and menarche status, at age 8-13 years (n = 120). We used linear and logistic regression to examine measures of trimester-specific in utero exposure as predictors of peripubertal hormone levels and pubertal onset, respectively. In secondary analyses, we evaluated estimated exposure at the midpoint of the first trimester and rates of change in exposure across pregnancy in relation to outcomes.ResultsSeveral phthalate metabolites measured throughout in utero development were associated with higher serum testosterone concentrations, while a number of metabolites measured in the third trimester were associated with higher DHEA-S. For example, an interquartile range (IQR) increase in mean monoethyl phthalate (MEP) levels across pregnancy was associated with 44% higher peripubertal testosterone (95% CI: 13-83%), while an IQR increase in di-2-ethylhexyl phthalate metabolites (ΣDEHP) specifically in the third trimester was associated with 25% higher DHEA-S (95%CI: 4.7-47%). In IQR increase in mean mono-2-ethylhexyl phthalate (MEHP) levels across pregnancy was associated with lower odds of having a Tanner Stage >1 for breast development (OR = 0.32, 95%CI: 0.11-0.95), while MEHP in the third trimester was associated with higher odds of having a Tanner Stage >1 for pubic hair development (OR = 3.76, 95%CI: 1.1-12.8). Results from secondary analyses were consistent with findings from our main analysis.ConclusionThese findings suggest that female reproductive development may be more vulnerable to the effects of phthalate or BPA exposure during specific critical periods of in utero development. This highlights the need for comprehensive characterizations of in utero exposure and consideration of windows of susceptibility in developmental epidemiological studies. Future research should consider repeated measures of in utero phthalate and BPA exposure within each trimester and across pregnancy.

Project description:BackgroundHealth care databases contain a wealth of information that can be used to develop programs and mature health care systems. There is concern that the sensitive nature of health data (eg, ethnicity, reproductive health, sexually transmitted infections, and lifestyle information) can have significant impact on individuals if misused, particularly among vulnerable and marginalized populations. As academic institutions, nongovernmental organizations, and international agencies begin to collaborate with low- and middle-income countries to develop and deploy health information technology (HIT), it is important to understand the technical and practical security implications of these initiatives.ObjectiveOur aim is to develop a conceptual framework for risk stratification of global health data partnerships and HIT projects. In addition to identifying key conceptual domains, we map each domain to a variety of publicly available indices that could be used to inform a quantitative model.MethodsWe conducted an overview of the literature to identify relevant publications, position statements, white papers, and reports. The research team reviewed all sources and used the framework method and conceptual framework analysis to name and categorize key concepts, integrate them into domains, and synthesize them into an overarching conceptual framework. Once key domains were identified, public international data sources were searched for relevant structured indices to generate quantitative counterparts.ResultsWe identified 5 key domains to inform our conceptual framework: State of HIT, Economics of Health Care, Demographics and Equity, Societal Freedom and Safety, and Partnership and Trust. Each of these domains was mapped to a number of structured indices.ConclusionsThere is a complex relationship among the legal, economic, and social domains of health care, which affects the state of HIT in low- and middle-income countries and associated data security risks. The strength of partnership and trust among collaborating organizations is an important moderating factor. Additional work is needed to formalize the assessment of partnership and trust and to develop a quantitative model of the conceptual framework that can help support organizational decision-making.

Project description:IntroductionEpidemiological studies linking dietary fat intake and obesity to breast cancer risk have produced inconsistent results. This may be due to the difficulty of dissociating fat intake from obesity, and/or the lack of defined periods of exposure in these studies. The pubertal mammary gland is highly sensitive to cancer-causing agents. We assessed how high fat diet (HFD) affects inflammation, proliferative, and developmental events in the pubertal gland, since dysregulation of these can promote mammary tumorigenesis. To test the effect of HFD initiated during puberty on tumorigenesis, we utilized BALB/c mice, for which HFD neither induces obesity nor metabolic syndrome, allowing dissociation of HFD effects from other conditions associated with HFD.MethodsPubertal BALB/c mice were fed a low fat diet (12% kcal fat) or a HFD (60% kcal fat), and subjected to carcinogen 7,12-dimethylbenz[a]anthracene (DMBA)-induced tumorigenesis.ResultsHFD elevated mammary gland expression of inflammatory and growth factor genes at 3 and 4 weeks of diet. Receptor activator of nuclear factor kappa-B ligand (RANKL), robustly induced at 4 weeks, has direct mitogenic activity in mammary epithelial cells and, as a potent inducer of NF-?B activity, may induce inflammatory genes. Three weeks of HFD induced a transient influx of eosinophils into the mammary gland, consistent with elevated inflammatory factors. At 10 weeks, prior to the appearance of palpable tumors, there were increased numbers of abnormal mammary epithelial lesions, enhanced cellular proliferation, increased growth factors, chemokines associated with immune-suppressive regulatory T cells, increased vascularization, and elevated M2 macrophages. HFD dramatically reduced tumor latency. Early developing tumors were more proliferative and were associated with increased levels of tumor-related growth factors, including increased plasma levels of HGF in tumor-bearing animals. Early HFD tumors also had increased vascularization, and more intra-tumor and stromal M2 macrophages.ConclusionsTaken together in this non-obesogenic context, HFD promotion of inflammatory processes, as well as local and systemically increased growth factor expression, are likely responsible for the enhanced tumorigenesis. It is noteworthy that although DMBA mutagenesis is virtually random in its targeting of genes in tumorigenesis, the short latency tumors arising in animals on HFD showed a unique gene expression profile, highlighting the potent overarching influence of HFD.

Dataset Information

Biomarkers for assessing reproductive development and health: Part 1--Pubertal development.

Publications

Biomarkers for assessing reproductive development and health: Part 1--Pubertal development.

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