Journal of Occupational & Environmental Medicine
Objective We examined associations between occupation and semen parameters in demonstrably fertil... more Objective We examined associations between occupation and semen parameters in demonstrably fertile men in the Study for Future Families. Methods Associations of occupation and workplace exposures with semen volume, sperm concentration, motility, and morphology were assessed using generalized linear modeling. Results Lower sperm concentration and motility were seen in installation, maintenance, and repair occupations. Higher exposure to lead, and to other toxicants, was seen in occupations with lower mean sperm concentrations (prevalence ratio for lead: 4.1; pesticides/insecticides: 1.6; solvents: 1.4). Working with lead for more than 3 months was associated with lower sperm concentration, as was lead exposure outside of work. Conclusions We found evidence in demonstrably fertile men for reduced sperm quality with lead, pesticide/herbicide, and solvent exposure. These results may identify occupations where protective measures against male reproductive toxicity might be warranted.
Rigorously standardized laboratory protocols and strict quality control (QC) are essential for me... more Rigorously standardized laboratory protocols and strict quality control (QC) are essential for meaningful comparisons between semen quality data from multiple sites. We describe our experience with the Study for Future Families (SFF), a multicenter study of semen quality in the United States. Detailed protocols were developed, and technicians from each study site attended a training session at the central laboratory. Technicians received blinded replicates from diluted semen specimens for counting by MicroCell and hemacytometer. Sperm motility was assessed using videotaped recordings for simple percent motility and categorical assessment of individual sperm progression as recommended by the World Health Organization (WHO). The mean intertechnician coefficient of variation for individual specimens was 12.6% for MicroCell counts, 15.2% for hemacytometer counts, and 10.5% for percent motility. Intratechnician coefficients of variation averaged 10.3% for MicroCell counts, 12.5% for hemacytometer counts, and 5.2% for percent motility. The average percent differences between the technicians' values and the central standard for individual specimens were 13.5%, 16.6%, and 11.9% for MicroCell counts, hemacytometer counts, and simple percent motility, respectively. We achieved our goal of maintaining mean intratechnician coefficients of variation and mean percent differences from the standard values of 15% or less for measurements of simple percent motility and sperm concentration by MicroCell. Standardization using the Improved Neubauer hemacytometer chamber proved more difficult. We were not successful in standardizing a method for categorical assessment of individual sperm progression.
Background: Di(2)ethyl hexyl phthalate (DEHP) and bisphenol A (BPA) are endocrine disrupting chem... more Background: Di(2)ethyl hexyl phthalate (DEHP) and bisphenol A (BPA) are endocrine disrupting chemicals that affect hormone physiology which leads to adverse reproductive and endocrine health outcom...
INTRODUCTION: Sex differences in play behavior have been seen in rodents, primates and humans wit... more INTRODUCTION: Sex differences in play behavior have been seen in rodents, primates and humans with literature showing some associations with maternal sex steroids. The PreSchool Activities Inventory (PSAI) is a validated tool to assess sexually-dimorphic play behavior. We assessed the associations between prenatal maternal estradiol (E2), free testosterone (fT) and total testosterone (T) and children’s PSAI scores at age 4. METHODS: Data were collected in The Infant Development and the Environment Study (TIDES), a US-based multi-center pregnancy cohort. The analysis included 399 pregnant women with complete data on sex steroids, PSAI and covariates. Early pregnancy E2 and T were analyzed by liquid chromatography tandem mass spectrometry and fT by equilibrium dialysis using labeled testosterone. PSAI scores (masculine, feminine and composite) were calculated from questionnaires completed by mothers when child was approximately 4 years old. Covariates included: maternal age and educat...
The Journal of clinical endocrinology and metabolism, Jun 9, 2017
Adequate sex steroid hormone concentrations are essential for normal fetal genital development in... more Adequate sex steroid hormone concentrations are essential for normal fetal genital development in early pregnancy. Our previous study demonstrated an inverse relationship between third trimester di-ethyl hexyl (DEHP) phthalate exposure and total testosterone (TT) concentrations. Here, we examine early pregnancy phthalates, sex steroid hormone concentrations, and newborn reproductive outcomes. We examined associations between urinary phthalate metabolite concentrations in early pregnancy and serum free testosterone (FT), TT, estrone (E1), and estradiol (E2) in 591 woman/infant dyads in The Infant Development and Environment Study; we also examined relationships between hormones and newborn genital outcomes using multiple regression models with covariate adjustment. E1 and E2 concentrations were 15-30% higher in relation to one unit increases in log mono-isobutyl phthalate (MiBP), mono-ethyl hexyl phthalate (MEHP), and mono-2-ethyl-5-oxy-hexyl phthalate (MOEHP) concentrations, and E2 ...
It is predicted that Japan and European Union will soon experience appreciable decreases in their... more It is predicted that Japan and European Union will soon experience appreciable decreases in their populations due to persistently low total fertility rates (TFR) below replacement level (2.1 child per woman). In the United States, where TFR has also declined, there are ethnic differences. Caucasians have rates below replacement, while TFRs among African-Americans and Hispanics are higher. We review possible links between TFR and trends in a range of male reproductive problems, including testicular cancer, disorders of sex development, cryptorchidism, hypospadias, low testosterone levels, poor semen quality, childlessness, changed sex ratio, and increasing demand for assisted reproductive techniques. We present evidence that several adult male reproductive problems arise in utero and are signs of testicular dysgenesis syndrome (TDS). Although TDS might result from genetic mutations, recent evidence suggests that it most often is related to environmental exposures of the fetal testis....
Paediatric and perinatal epidemiology, Jan 17, 2015
Prenatal phthalate exposure is associated with altered male reproductive tract development, and i... more Prenatal phthalate exposure is associated with altered male reproductive tract development, and in particular, shorter anogenital distance (AGD). AGD, a sexually dimorphic index of prenatal androgen exposure, may also be altered by prenatal stress. How these exposures interact to impact AGD is unknown. Here, we examine the extent to which associations between prenatal phthalate exposure and infant AGD are modified by prenatal exposure to stressful life events (SLEs). Phthalate metabolites [including those of diethylhexyl phthalate (DEHP) and their molar sum (ΣDEHP)] were measured in first trimester urine from 738 pregnant women participating in The Infant Development and the Environment Study (TIDES). Women completed questionnaires on SLEs, and permitted infant AGD measurements at birth. Subjects were classified as 'lower' and 'higher' stress (0 first trimester SLEs vs. 1+).We estimated relationships between phthalate concentrations and AGD (by infant sex and stress ...
The Journal of clinical endocrinology and metabolism, Jan 22, 2015
Prenatal exposure to phthalates disrupts male sex development in rodents. In humans, the placenta... more Prenatal exposure to phthalates disrupts male sex development in rodents. In humans, the placental glycoprotein hormone human chorionic gonadotropin (hCG) is required for male development, and may be a target of phthalate exposure. To test the hypothesis that phthalates disrupt placental hCG differentially in males and females with consequences for sexually dimorphic genital development. The Infant Development and Environment Study (TIDES) is a prospective birth cohort. Pregnant women were enrolled from 2010-2012 at 4 university hospitals. A subset of TIDES subjects (n=541/753) for whom genital and phthalate measurements were available and who underwent prenatal serum screening in the first or second trimester Main Outcome Measures: hCG levels in maternal serum in the first and second trimesters and anogenital distance (AGD), the distance from the anus to the genitals, in male and female neonates. Higher first trimester urinary mono-n-butyl phthalate (MnBP, p=0.01), monobenzyl phtha...
Phthalates, a ubiquitous class of environmental chemicals, may interfere with typical reproductiv... more Phthalates, a ubiquitous class of environmental chemicals, may interfere with typical reproductive hormone production both in utero and in adulthood. Although they are best known as anti-androgens, increasingly, evidence suggests that phthalates, particularly di-2-ethylhexyl phthalate (DEHP), may also suppress estrogen production. Given that both androgens and estrogens are essential for sexual function, particularly sexual interest, it is plausible that adult exposure to phthalates alters sexual function. To this end, we used data from 360 women participating in a pregnancy cohort study (the Study for Future Families) to examine whether urinary phthalate metabolite concentrations were associated with two dimensions of self-reported sexual dysfunction in the months prior to conception: lack of sexual interest and vaginal dryness. Women in the highest quartile of urinary concentrations of mono-2-ethyl-5-hydroxyhexyl phthalate, a DEHP metabolite, had 2.58 (95% CI 1.33, 5.00) times the...
Journal of Occupational & Environmental Medicine
Objective We examined associations between occupation and semen parameters in demonstrably fertil... more Objective We examined associations between occupation and semen parameters in demonstrably fertile men in the Study for Future Families. Methods Associations of occupation and workplace exposures with semen volume, sperm concentration, motility, and morphology were assessed using generalized linear modeling. Results Lower sperm concentration and motility were seen in installation, maintenance, and repair occupations. Higher exposure to lead, and to other toxicants, was seen in occupations with lower mean sperm concentrations (prevalence ratio for lead: 4.1; pesticides/insecticides: 1.6; solvents: 1.4). Working with lead for more than 3 months was associated with lower sperm concentration, as was lead exposure outside of work. Conclusions We found evidence in demonstrably fertile men for reduced sperm quality with lead, pesticide/herbicide, and solvent exposure. These results may identify occupations where protective measures against male reproductive toxicity might be warranted.
Rigorously standardized laboratory protocols and strict quality control (QC) are essential for me... more Rigorously standardized laboratory protocols and strict quality control (QC) are essential for meaningful comparisons between semen quality data from multiple sites. We describe our experience with the Study for Future Families (SFF), a multicenter study of semen quality in the United States. Detailed protocols were developed, and technicians from each study site attended a training session at the central laboratory. Technicians received blinded replicates from diluted semen specimens for counting by MicroCell and hemacytometer. Sperm motility was assessed using videotaped recordings for simple percent motility and categorical assessment of individual sperm progression as recommended by the World Health Organization (WHO). The mean intertechnician coefficient of variation for individual specimens was 12.6% for MicroCell counts, 15.2% for hemacytometer counts, and 10.5% for percent motility. Intratechnician coefficients of variation averaged 10.3% for MicroCell counts, 12.5% for hemacytometer counts, and 5.2% for percent motility. The average percent differences between the technicians' values and the central standard for individual specimens were 13.5%, 16.6%, and 11.9% for MicroCell counts, hemacytometer counts, and simple percent motility, respectively. We achieved our goal of maintaining mean intratechnician coefficients of variation and mean percent differences from the standard values of 15% or less for measurements of simple percent motility and sperm concentration by MicroCell. Standardization using the Improved Neubauer hemacytometer chamber proved more difficult. We were not successful in standardizing a method for categorical assessment of individual sperm progression.
Background: Di(2)ethyl hexyl phthalate (DEHP) and bisphenol A (BPA) are endocrine disrupting chem... more Background: Di(2)ethyl hexyl phthalate (DEHP) and bisphenol A (BPA) are endocrine disrupting chemicals that affect hormone physiology which leads to adverse reproductive and endocrine health outcom...
INTRODUCTION: Sex differences in play behavior have been seen in rodents, primates and humans wit... more INTRODUCTION: Sex differences in play behavior have been seen in rodents, primates and humans with literature showing some associations with maternal sex steroids. The PreSchool Activities Inventory (PSAI) is a validated tool to assess sexually-dimorphic play behavior. We assessed the associations between prenatal maternal estradiol (E2), free testosterone (fT) and total testosterone (T) and children’s PSAI scores at age 4. METHODS: Data were collected in The Infant Development and the Environment Study (TIDES), a US-based multi-center pregnancy cohort. The analysis included 399 pregnant women with complete data on sex steroids, PSAI and covariates. Early pregnancy E2 and T were analyzed by liquid chromatography tandem mass spectrometry and fT by equilibrium dialysis using labeled testosterone. PSAI scores (masculine, feminine and composite) were calculated from questionnaires completed by mothers when child was approximately 4 years old. Covariates included: maternal age and educat...
The Journal of clinical endocrinology and metabolism, Jun 9, 2017
Adequate sex steroid hormone concentrations are essential for normal fetal genital development in... more Adequate sex steroid hormone concentrations are essential for normal fetal genital development in early pregnancy. Our previous study demonstrated an inverse relationship between third trimester di-ethyl hexyl (DEHP) phthalate exposure and total testosterone (TT) concentrations. Here, we examine early pregnancy phthalates, sex steroid hormone concentrations, and newborn reproductive outcomes. We examined associations between urinary phthalate metabolite concentrations in early pregnancy and serum free testosterone (FT), TT, estrone (E1), and estradiol (E2) in 591 woman/infant dyads in The Infant Development and Environment Study; we also examined relationships between hormones and newborn genital outcomes using multiple regression models with covariate adjustment. E1 and E2 concentrations were 15-30% higher in relation to one unit increases in log mono-isobutyl phthalate (MiBP), mono-ethyl hexyl phthalate (MEHP), and mono-2-ethyl-5-oxy-hexyl phthalate (MOEHP) concentrations, and E2 ...
It is predicted that Japan and European Union will soon experience appreciable decreases in their... more It is predicted that Japan and European Union will soon experience appreciable decreases in their populations due to persistently low total fertility rates (TFR) below replacement level (2.1 child per woman). In the United States, where TFR has also declined, there are ethnic differences. Caucasians have rates below replacement, while TFRs among African-Americans and Hispanics are higher. We review possible links between TFR and trends in a range of male reproductive problems, including testicular cancer, disorders of sex development, cryptorchidism, hypospadias, low testosterone levels, poor semen quality, childlessness, changed sex ratio, and increasing demand for assisted reproductive techniques. We present evidence that several adult male reproductive problems arise in utero and are signs of testicular dysgenesis syndrome (TDS). Although TDS might result from genetic mutations, recent evidence suggests that it most often is related to environmental exposures of the fetal testis....
Paediatric and perinatal epidemiology, Jan 17, 2015
Prenatal phthalate exposure is associated with altered male reproductive tract development, and i... more Prenatal phthalate exposure is associated with altered male reproductive tract development, and in particular, shorter anogenital distance (AGD). AGD, a sexually dimorphic index of prenatal androgen exposure, may also be altered by prenatal stress. How these exposures interact to impact AGD is unknown. Here, we examine the extent to which associations between prenatal phthalate exposure and infant AGD are modified by prenatal exposure to stressful life events (SLEs). Phthalate metabolites [including those of diethylhexyl phthalate (DEHP) and their molar sum (ΣDEHP)] were measured in first trimester urine from 738 pregnant women participating in The Infant Development and the Environment Study (TIDES). Women completed questionnaires on SLEs, and permitted infant AGD measurements at birth. Subjects were classified as 'lower' and 'higher' stress (0 first trimester SLEs vs. 1+).We estimated relationships between phthalate concentrations and AGD (by infant sex and stress ...
The Journal of clinical endocrinology and metabolism, Jan 22, 2015
Prenatal exposure to phthalates disrupts male sex development in rodents. In humans, the placenta... more Prenatal exposure to phthalates disrupts male sex development in rodents. In humans, the placental glycoprotein hormone human chorionic gonadotropin (hCG) is required for male development, and may be a target of phthalate exposure. To test the hypothesis that phthalates disrupt placental hCG differentially in males and females with consequences for sexually dimorphic genital development. The Infant Development and Environment Study (TIDES) is a prospective birth cohort. Pregnant women were enrolled from 2010-2012 at 4 university hospitals. A subset of TIDES subjects (n=541/753) for whom genital and phthalate measurements were available and who underwent prenatal serum screening in the first or second trimester Main Outcome Measures: hCG levels in maternal serum in the first and second trimesters and anogenital distance (AGD), the distance from the anus to the genitals, in male and female neonates. Higher first trimester urinary mono-n-butyl phthalate (MnBP, p=0.01), monobenzyl phtha...
Phthalates, a ubiquitous class of environmental chemicals, may interfere with typical reproductiv... more Phthalates, a ubiquitous class of environmental chemicals, may interfere with typical reproductive hormone production both in utero and in adulthood. Although they are best known as anti-androgens, increasingly, evidence suggests that phthalates, particularly di-2-ethylhexyl phthalate (DEHP), may also suppress estrogen production. Given that both androgens and estrogens are essential for sexual function, particularly sexual interest, it is plausible that adult exposure to phthalates alters sexual function. To this end, we used data from 360 women participating in a pregnancy cohort study (the Study for Future Families) to examine whether urinary phthalate metabolite concentrations were associated with two dimensions of self-reported sexual dysfunction in the months prior to conception: lack of sexual interest and vaginal dryness. Women in the highest quartile of urinary concentrations of mono-2-ethyl-5-hydroxyhexyl phthalate, a DEHP metabolite, had 2.58 (95% CI 1.33, 5.00) times the...
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Papers by Shanna Swan