Association analysis between mixed exposure to phenols and semen quality

doi:10.3724/SP.J.1123.2023.09009

Abstract

Abstract:

Phenols such as bisphenols, parabens, and triclosan are common environmental endocrine disruptors. Previous epidemiological studies have suggested that phenols may affect semen quality, but the results were inconsistent. In addition, most existing studies have been limited to the effects of a single chemical compound, ignoring the health effects of mixed exposure to multiple chemicals. Thus, we aimed to explore the associations between individual and mixed exposure to phenols and various semen quality parameters.

In this study, a rapid and sensitive method was used to determine 18 phenolic compounds in urine samples of 799 volunteers who donated sperm samples to the Shanghai Human Sperm Bank. A spot urine sample was collected from each subject on the day of their clinic visit and stored at -20 ℃ until testing. Urine samples (200 μL) were extracted and added with 20 μL of an internal standard and 50 μL of β-glucuronidase solution. The mixtures were then incubated for 12 h at 37 ℃. After hydrolysis, the samples were extracted twice using ethyl acetate (500 μL). The concentrations of the 18 phenolic compounds were measured using high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Semen quality parameters were analyzed using a computer-aided semen analyzer. Multiple linear regressions were used to detect the associations between individual phenol exposure and semen quality parameters. In addition, weighted quantile sum (WQS) models were used to explore the associations between mixed-phenol exposure and semen quality parameters. After adjusting for potential covariates, the results of multiple linear regressions showed that exposure to ethyl paraben (EtP) was significantly negatively associated with sperm concentration and total sperm count (P<0.05). In addition, exposure to mixed phenols was significantly associated with decreased sperm concentration; methyl paraben (MeP) and EtP were identified as the main contributors to this decrease. Thus, phenol exposure may be associated with decreased semen quality in young males, particularly with respect to sperm concentration and total sperm count.

Key words: high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS), phenols, semen quality, mixed exposure, male reproductive health

CLC Number:

O658

SHEN Xiaoli, TANG Weifeng, LIU Junxia, AO Junjie, LIU Xiaoning, HUANG Xian, QIU Jin, ZHANG Jun, ZHANG Qianlong. Association analysis between mixed exposure to phenols and semen quality[J]. Chinese Journal of Chromatography, 2024, 42(2): 203-210.

Figures/Tables 6

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Characteristic	n		(%)
Abstinence time/d
<3	178		(22.3)
3-8	590		(73.8)
≥8	31		(3.9)
Smoking status
Never	580		(72.6)
Former	105		(13.1)
Current	114		(14.3)
Alcohol consumption
Never	219		(27.4)
Occasionally	518		(64.8)
Usually	62		(7.8)
Educational level
Below bachelor	282		(35.3)
At bachelor	353		(44.2)
Above bachelor	164		(20.5)
Age/years (Mean±SD)^*		26.11±5.70
BMI/(kg/m²) (Mean±SD)^*		22.92±2.77
Creatinine/(μmol/L) (Mean±SD)^*		12187±7394

Characteristic	n		(%)
Abstinence time/d
<3	178		(22.3)
3-8	590		(73.8)
≥8	31		(3.9)
Smoking status
Never	580		(72.6)
Former	105		(13.1)
Current	114		(14.3)
Alcohol consumption
Never	219		(27.4)
Occasionally	518		(64.8)
Usually	62		(7.8)
Educational level
Below bachelor	282		(35.3)
At bachelor	353		(44.2)
Above bachelor	164		(20.5)
Age/years (Mean±SD)^*		26.11±5.70
BMI/(kg/m²) (Mean±SD)^*		22.92±2.77
Creatinine/(μmol/L) (Mean±SD)^*		12187±7394

Compound	LOD/ (ng/mL)	Mass concentrations of phenols/(ng/mL)							Detection rate/%
Compound	LOD/ (ng/mL)	Min	Max	P10	P25	Median	P75	P90	Detection rate/%
Bisphenols (BP)
BPA	0.08	<LOD	43.22	0.01	0.20	0.56	1.63	4.08	85.73
BPS	0.003	<LOD	270.05	0.02	0.05	0.23	0.70	1.44	94.99
BPB	0.0003	<LOD	0.90	<LOD	0.003	0.01	0.03	0.08	84.98
BPP	0.0001	<LOD	15.21	<LOD	0.004	0.02	0.08	0.27	81.10
BPAP	0.002	<LOD	4.59	<LOD	0.004	0.02	0.06	0.17	81.98
BPAF	0.001	<LOD	0.66	<LOD	<LOD	<LOD	0.02	0.05	35.79
BPZ	0.01	<LOD	0.60	<LOD	<LOD	<LOD	0.03	0.06	48.69
Parabens
MeP	0.002	0.033	599.87	1.58	3.23	8.73	28.53	72.76	100
EtP	0.005	<LOD	1603.10	<LOD	1.40	2.49	5.47	15.41	84.61
PrP	0.0005	<LOD	568.01	0.15	0.71	2.65	8.84	26.28	93.37
BzP	0.003	<LOD	0.22	<LOD	<LOD	<LOD	<LOD	0.005	16.02
BuP	0.002	<LOD	68.95	<LOD	<LOD	<LOD	<LOD	0.01	23.53
HeP	0.002	<LOD	0.18	<LOD	<LOD	<LOD	<LOD	<LOD	9.89
Benzophenones
BP-1	0.005	<LOD	131.99	<LOD	0.01	0.02	0.08	0.28	78.35
BP-2	0.002	<LOD	25.01	<LOD	<LOD	<LOD	0.01	0.02	36.92
BP-8	0.05	<LOD	25.02	<LOD	<LOD	<LOD	0.07	0.54	29.54
4-HBP	0.01	<LOD	3.04	<LOD	0.01	0.04	0.09	0.22	75.47
Antimicrobial
TCS	0.002	<LOD	342.89	0.01	0.09	0.31	1.09	6.44	91.24

Compound	LOD/ (ng/mL)	Mass concentrations of phenols/(ng/mL)							Detection rate/%
Compound	LOD/ (ng/mL)	Min	Max	P10	P25	Median	P75	P90	Detection rate/%
Bisphenols (BP)
BPA	0.08	<LOD	43.22	0.01	0.20	0.56	1.63	4.08	85.73
BPS	0.003	<LOD	270.05	0.02	0.05	0.23	0.70	1.44	94.99
BPB	0.0003	<LOD	0.90	<LOD	0.003	0.01	0.03	0.08	84.98
BPP	0.0001	<LOD	15.21	<LOD	0.004	0.02	0.08	0.27	81.10
BPAP	0.002	<LOD	4.59	<LOD	0.004	0.02	0.06	0.17	81.98
BPAF	0.001	<LOD	0.66	<LOD	<LOD	<LOD	0.02	0.05	35.79
BPZ	0.01	<LOD	0.60	<LOD	<LOD	<LOD	0.03	0.06	48.69
Parabens
MeP	0.002	0.033	599.87	1.58	3.23	8.73	28.53	72.76	100
EtP	0.005	<LOD	1603.10	<LOD	1.40	2.49	5.47	15.41	84.61
PrP	0.0005	<LOD	568.01	0.15	0.71	2.65	8.84	26.28	93.37
BzP	0.003	<LOD	0.22	<LOD	<LOD	<LOD	<LOD	0.005	16.02
BuP	0.002	<LOD	68.95	<LOD	<LOD	<LOD	<LOD	0.01	23.53
HeP	0.002	<LOD	0.18	<LOD	<LOD	<LOD	<LOD	<LOD	9.89
Benzophenones
BP-1	0.005	<LOD	131.99	<LOD	0.01	0.02	0.08	0.28	78.35
BP-2	0.002	<LOD	25.01	<LOD	<LOD	<LOD	0.01	0.02	36.92
BP-8	0.05	<LOD	25.02	<LOD	<LOD	<LOD	0.07	0.54	29.54
4-HBP	0.01	<LOD	3.04	<LOD	0.01	0.04	0.09	0.22	75.47
Antimicrobial
TCS	0.002	<LOD	342.89	0.01	0.09	0.31	1.09	6.44	91.24

Compound	β (95% CI)^a)
	Semen concentration^b)		Total sperm count^b)		Semen volume		Progressive motility
	Crude	Adjusted	Crude	Adjusted	Crude	Adjusted	Crude	Adjusted
Bisphenol
BPA	-0.003 (-0.037, 0.031)	0.002 (-0.035, 0.039)	-0.019 (-0.064, 0.026)	0.004 (-0.041, 0.049)	-0.018 (-0.090, 0.054)	0.023 (-0.054, 0.100)	0.188 (-0.551, 0.927)	-0.025 (-0.827, 0.777)
BPS	-0.020 (-0.046, 0.006)	-0.019 (-0.047, 0.009)	-0.033 (-0.068, 0.002)	-0.031 (-0.066, 0.004)	-0.031 (-0.087, 0.025)	-0.029 (-0.087, 0.029)	0.368 (-0.210, 0.946)	0.279 (-0.325, 0.883)
BPB	-0.014 (-0.039, 0.011)	-0.010 (-0.038, 0.018)	-0.031 (-0.064, 0.002)	-0.007 (-0.040, 0.026)	-0.012 (-0.065, 0.041)	0.039 (-0.019, 0.097)	-0.070 (-0.614, 0.474)	-0.212 (-0.812, 0.388)
BPP	-0.004 (-0.021, 0.013)	-0.001 (-0.020, 0.018)	-0.015 (-0.038, 0.008)	-0.001 (-0.024, 0.022)	-0.020 (-0.057, 0.017)	0.004 (-0.036, 0.044)	0.068 (-0.311, 0.447)	-0.004 (-0.418, 0.410)
BPAP	-0.004 (-0.032, 0.024)	0.000 (-0.030, 0.030)	-0.015 (-0.052, 0.022)	-0.002 (-0.039, 0.035)	-0.018 (-0.077, 0.041)	0.003 (-0.060, 0.066)	-0.177 (-0.791, 0.437)	-0.394 (-1.047, 0.259)
Paraben
MeP	-0.029 (-0.062, 0.004)	-0.028 (-0.063, 0.007)	-0.024 (-0.068, 0.020)	-0.010 (-0.054, 0.034)	0.015 (-0.056, 0.086)	0.043 (-0.030, 0.116)	0.241 (-0.487, 0.969)	0.240 (-0.514, 0.994)
EtP	-0.022 (-0.040, -0.004)	-0.023 (-0.041, -0.005)	-0.039 (-0.062, -0.016)	-0.036 (-0.059, -0.013)	-0.052 (-0.089, -0.015)	-0.042 (-0.080, -0.004)	0.050 (-0.338, 0.438)	-0.015 (-0.407, 0.377)
PrP	-0.014 (-0.032, 0.004)	-0.013 (-0.031, 0.005)	-0.014 (-0.037, 0.009)	-0.006 (-0.029, 0.017)	0.003 (-0.034, 0.040)	0.020 (-0.018, 0.058)	-0.150 (-0.536, 0.236)	-0.154 (-0.551, 0.243)
TCS	0.011 (-0.009, 0.031)	0.010 (-0.011, 0.031)	0.015 (-0.012, 0.042)	0.012 (-0.015, 0.039)	-0.007 (-0.050, 0.036)	-0.008 (-0.051, 0.035)	0.165 (-0.278, 0.608)	0.141 (-0.307, 0.589)