Document Type

Campus-Only Access for One (1) Year

Embargo Period

4-10-2017

Degree Program

Public Health

Degree Type

Master of Science (M.S.)

Year Degree Awarded

2017

Month Degree Awarded

May

Advisor Name

J. Richard Pilsner

Advisor Middle Initial

Richard

Advisor Last Name

Pilsner

Abstract

INTRODUCTION

Phthalates, a chemical class of plasticizers, are ubiquitous in the environment and recognized

as endocrine disrupting compounds (EDCs). Recent data suggest that oxidative stress is a

potential mediator of poor male reproductive health associated with phthalate exposure.

Mitochondria are implicated in the production of excess oxidative stress and sperm

mitochondrial copy number (MtCopy) and deletions (MtDeletion) have been linked with

male infertility. However, little is known about the relationship of these mitochondrial

biomarkers in sperm with phthalate exposure and oxidative stress.

OBJECTIVES

To examine associations of urinary phthalate metabolites and isoprostane concentrations on

sperm MtCopy and MtDeletions in male partners undergoing assisted reproductive

technologies (ART).

METHODS

A total of (n=97) sperm samples were collected from male partners undergoing ART at

Baystate Medical Center, in Springfield, MA from 2014 to 2016 as part of the Sperm

Environmental Epigenetics and Development Study (SEEDS). Seventeen urinary phthalate

metabolites (n=103) were analyzed by the Centers for Disease Control using tandem mass

spectrometry. 15-F2t-Isoprostane (n=101) was measured using a competitive enzyme-linked

immonsorbent assay in urine of male individuals. A triplex Taqman probe-based qPCR

method was developed for relative quantification of genomic DNA, MtCopy and

MtDeletions. Multivariable linear or logistic regression was employed to examine

associations with age, BMI, batch and current smoking status with each outcome to

determine confounders used for adjustment.

RESULTS

Quartiles of MtCopy and MtDeletion were positively associated with the odds of male

infertility (p for trend < .0001 and 0.007, respectively). Urinary metabolite concentrations of

MCNP displayed a positive association with MtCopy (β=1.56; p =0.03). Urinary MEHP

concentrations were positively associated with MtDeletion in only infertile individuals

(n=30) (β = 0.075; p = 0.006). Urinary isoprostane concentration was not associated with

MtCopy or MtDeletion, but was associated with seven phthalate metabolite concentrations

(MEOHP, MEHHP, MBzP, MHBP, MiBP, and MHiBP).

CONCLUSIONS

To our knowledge, this is the first study to investigate the relationship between sperm

MtCopy and MtDeletion with oxidative stress and phthalates. These results suggest that

certain phthalate metabolites may be associated with a known biomarker of systemic

oxidative stress. Sperm mitochondrial function as measured by MtCopy and MtDeletion may

be considered biomarkers of male infertility, although no relationship was shown between

mitochondrial outcomes and oxidative stress. Future research is investigating these

relationships with developmental outcomes including embryo quality.

First Advisor

J. Richard Pilsner

Second Advisor

Alexander Suvorov

Third Advisor

Krystal Pollitt

Fourth Advisor

Brian W. Whitcomb

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