Endocrine Modulation & Metal Exposure: Long Term Effects on the Children of Agricultural Working Mothers in Thailand 公开

Walter, Grant Arthur (2015)

Permanent URL: https://etd.library.emory.edu/concern/etds/5t34sj73g?locale=zh
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Abstract

Changes in pubertal timing (precocious/delayed) increases risks for specific outcomes in both genders. Characterization of factors modulating timing of puberty has produced evidence suggesting a role of environmental exposure. Previous studies correlated delayed puberty and environmental toxicants, specifically heavy metals (HMs) but the mode of toxicity is unknown. Animal studies have shown possibilities with HM exposure and puberty modulation. Large focus has been framed around the Hypothalamic-pituitary-gonadal (HPG) axis. HMs have shown in multiple animal, and few human, studies to affect hormone production released from the axis, especially Luteinizing Hormone (LH). The HPG axis begins development during embryogenesis but whether HM exposure during this critical window of development and subsequent effects still needs answering. To answer this, the Study of Asian Women And their offSpring's Development and Environmental Exposures (SAWASDEE) birth cohort was used. Metal concentrations were measured over pregnancy and compared to neonatal LH and anthropometrics. Measurement of metals was performed through ICP-MS and LH through EIA. Comparison was made through multivariate linear and logistic regression. Adjusted average maternal HM concentration for individual HMs and LH logistic regression yielded ORs of 0.59 (0.07, 4.69), 0.04(<0.01, 1.03), 0.44(0.04, 5.30) and 2.55(0.48, 13.49) for Pb, Cd, As and Hg, respectively. Earliest individual maternal HM concentrations showed adjusted ORs of 1.37 (0.14, 13.35) for Pb, 0.54 (0.06, 4.90) for Cd, 0.94 (0.19, 4.68) for As and 0.99(0.32, 3.00) for Hg. Only Cd showed significant point estimates but lost this status after adjustment for other variables deemed important. This study is the first study looking at HM exposure and neonatal hormone release from the HPG axis. Findings suggest that HMs do modulate LH release in neonates at birth. Caution, however, should be used when interpreting results from this study. Use of the SAWASDEE birth cohort was originally intended to study organophosphate insecticide exposure and subsequent neurodevelopment. Information and samples were taken in regard to the aforementioned study and complicate the interpretive ability found from results here. Estimates and prevalence found have applicability in construction of future study sampling calculations and timing of sample collection for adequate study.

Table of Contents

Table of Contents

Background and Significance 1

Modulation of puberty and health outcomes 1

Known health outcomes for heavy metal exposure 1

Developing area of toxicity 2

Timing of exposure to heavy metals 3

Window of vulnerability 3

Pubertal development 4

Lead, Mercury, Arsenic and Cadmium in the Axis 5

Initiation of puberty and in-utero development 6

Hypothesis 6

Methods 7

Participants and recruitment 7

Exposure assessment 8

Outcome assessment 10

Statistical assessment 10

Results 12

Basic demographics 12

Occupational categories 12

Accuracy and precision 13

Exposure, confounder and outcome summary 13

Primary outcome 14

Secondary outcome 15

Discussion 18

Maternal exposure 18

Fetal exposure 19

Outcome interpretation 20

Limitations 22

Conclusions 23

References 25

Appendix 29

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