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Open Access Thesis
Master of Science (M.S.)
Year Degree Awarded
Month Degree Awarded
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.
To examine associations of urinary phthalate metabolites and isoprostane concentrations on
sperm MtCopy and MtDeletions in male partners undergoing assisted reproductive
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.
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).
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.
Richard J. Pilsner
Olmsted, Alexandra, "Sperm Mitochondrial Copy Number and Associations with Oxidative Stress and Phthalate Metabolites in Male Partners Undergoing Assisted Reproductive Technologies" (2017). Masters Theses. 547.