Semen quality and insulin-like factor 3: Associations with urinary and seminal levels of phthalate metabolites in adult males.
Certain phthalates have adverse effects on male reproductive functions in animals, and potentially affect human testicular function and spermatogenesis, but little is known about the active mechanisms. We measured the urinary and seminal phthalate metabolites and explored their associations on insulin-like factor 3 (INSL3) and semen quality. Urine, blood, and semen samples were collected from the male partners of subfertile (n = 253) and fertile (n = 37) couples in a reproductive center in southern Taiwan. INSL3, reproductive hormones, semen-quality, and 11 phthalate metabolites in urine and semen were measured. There were significant correlations in the distribution pattern of metabolites, such as the relative contribution of low or high molecular weight phthalate metabolites. The significantly monotonic trends in semen volume, sperm concentration and motility were associated with increasing quartiles of INSL3 (all p-trend < 0.001). In adjusted regression models, increases in urinary phthalate metabolites levels were adversely associated with sperm concentration (monobenzyl phthalate [MBzP], mono-2-ethylhexyl phthalate [MEHP] and MEHP%), motility (MBzP and MEHP) and INSL3 (MBzP, MEHP and MEHP%) (all p < 0.01). Higher seminal phthalate metabolite levels were associated with decreases in sperm concentration (MEHP and mono-2-ethyl-5-hydroxyhexyl phthalate), motility (mono-ethyl phthalate [MEP] and di-(2-ethylhexyl) phthalate [DEHP] metabolites), normal morphology (MEP), and INSL3 (monomethyl phthalate and MEP) (all p < 0.05). Our data suggest that INSL3 secretion, reproductive hormone balance, and sperm production and quality might be simultaneously adversely affected for individuals excreting increasing levels of phthalates metabolites (especially di-ethyl phthalate, butylbenzyl phthalate, and DEHP) in urine and semen samples.
Department of Environmental and Occupational Health, College of Medicine, National Cheng Kung University, 138 Sheng-Li Road, Tainan 70403, Taiwan. Electronic address: s7897104@mail.ncku.edu.tw.
Wei-Hsiang
WH
Chang
Department of Obstetrics and Gynecology, Hospital of National Cheng Kung University, 138 Sheng-Li Road, Tainan 70403, Taiwan. Electronic address: mhwu68@mail.ncku.edu.tw.
Meng-Hsing
MH
Wu
An-An Women and Children Clinic, 286 Kaiyuan Road, Tainan 70403, Taiwan. Electronic address: ivfartpan@gmail.com.
Hsien-An
HA
Pan
Department of Obstetrics and Gynecology, Hospital of National Cheng Kung University, 138 Sheng-Li Road, Tainan 70403, Taiwan. Electronic address: paolink@mail.ncku.edu.tw.
Pao-Lin
PL
Guo
Department of Environmental and Occupational Health, College of Medicine, National Cheng Kung University, 138 Sheng-Li Road, Tainan 70403, Taiwan; Research Center of Environmental Trace Toxic Substance, National Cheng Kung University, 138 Sheng-Li Road, Tainan 70403, Taiwan. Electronic address: cclee@mail.ncku.edu.tw.
Ching-Chang
CC
Lee
D000328:Adult; D003430:Cross-Sectional Studies; D004051:Diethylhexyl Phthalate / Q000031:analogs & derivatives / Q000032:analysis / Q000378:metabolism; D005298:Fertility; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D008297:Male; D010795:Phthalic Acids / Q000032:analysis* / Q000378:metabolism; D011506:Proteins / Q000378:metabolism*; D011863:Radioimmunoassay; D012098:Reproduction; D055101:Semen Analysis / Q000379:methods*; D013094:Spermatozoa / Q000378:metabolism; D013624:Taiwan; D013739:Testosterone / Q000378:metabolism*; D016482:Urinalysis / Q000379:methods*
D007328:Insulin; C084797:Leydig insulin-like protein; D010795:Phthalic Acids; D011506:Proteins; C479069:mono(2-ethyl-5-hydroxyhexyl) phthalate; C517284:monomethyl phthalate; D013739:Testosterone; C032279:phthalic acid; D004051:Diethylhexyl Phthalate; C016599:mono-(2-ethylhexyl)phthalate; C027561:butylbenzyl phthalate
Biomarkers; Insulin-like factor 3; Phthalate metabolites; Semen quality; Testicular function