Female Reproductive Impacts - HH-RA.org

Bibliography Tag: female reproductive impacts

Crews et al., 2007

David Crews, Andrea C. Gore, Timothy S. Hsu, Nygerma L. Dangleben, Michael Spinetta, Timothy Schallert, Matthew D. Anway, and Michael K. Skinner, “Transgenerational epigenetic imprints on mate preference,” PNAS, 2007, 104:14, DOI: 10.1073/PNAS.0610410104.

ABSTRACT:

Environmental contamination by endocrine-disrupting chemicals (EDC) can have epigenetic effects (by DNA methylation) on the germ line and promote disease across subsequent generations. In natural populations, both sexes may encounter affected as well as unaffected individuals during the breeding season, and any diminution in attractiveness could compromise reproductive success. Here we examine mate preference in male and female rats whose progenitors had been treated with the antiandrogenic fungicide vinclozolin. This effect is sex-specific, and we demonstrate that females three generations removed from the exposure discriminate and prefer males who do not have a history of exposure, whereas similarly epigenetically imprinted males do not exhibit such a preference. The observations suggest that the consequences of EDCs are not just transgenerational but can be ‘‘transpopulational’’, because in many mammalian species, males are the dispersing sex. This result indicates that epigenetic transgenerational inheritance of EDC action represents an unappreciated force in sexual selection. Our observations provide direct experimental evidence for a role of epigenetics as a determinant factor in evolution. FULL TEXT

Manikkam et al., 2014

Mohan Manikkam, M. Muksitul Haque, Carlos Guerrero-Bosagna, Eric E. Nilsson, Michael K. Skinner , “Pesticide Methoxychlor Promotes the Epigenetic Transgenerational Inheritance of Adult-Onset Disease through the Female Germline,” PLoS ONE, 2014, 9:7, DOI: 10.371/JOURNAL.PONE.0102091.

ABSTRACT:

Environmental compounds including fungicides, plastics, pesticides, dioxin and hydrocarbons can promote the epigenetic transgenerational inheritance of adult-onset disease in future generation progeny following ancestral exposure during the critical period of fetal gonadal sex determination. This study examined the actions of the pesticide methoxychlor to promote the epigenetic transgenerational inheritance of adult-onset disease and associated differential DNA methylation regions (i.e. epimutations) in sperm. Gestating F0 generation female rats were transiently exposed to methoxychlor during fetal gonadal development (gestation days 8 to 14) and then adult-onset disease was evaluated in adult F1 and F3 (great-grand offspring) generation progeny for control (vehicle exposed) and methoxychlor lineage offspring. There were increases in the incidence of kidney disease, ovary disease, and obesity in the methoxychlor lineage animals. In females and males the incidence of disease increased in both the F1 and the F3 generations and the incidence of multiple disease increased in the F3 generation. There was increased disease incidence in F4 generation reverse outcross (female) offspring indicating disease transmission was primarily transmitted through the female germline. Analysis of the F3 generation sperm epigenome of the methoxychlor lineage males identified differentially DNA methylated regions (DMR) termed epimutations in a genome-wide gene promoters analysis. These epimutations were found to be methoxychlor exposure specific in comparison with other exposure specific sperm epimutation signatures. Observations indicate that the pesticide methoxychlor has the potential to promote the epigenetic transgenerational inheritance of disease and the sperm epimutations appear to provide exposure specific epigenetic biomarkers for transgenerational disease and ancestral environmental exposures. FULL TEXT

Chevrier et al., 2011

Cecile Chevrier, Gwendolina Limon, Christine Monfort, Florence Rouget, Ronan Garlantezec, et al., “Urinary biomarkers of prenatal atrazine exposure and adverse birth outcomes in the PELAGIE birth cohort,” Environmental Health Perspectives, 2011, 119:7, DOI: 10.1289/EHP.100277.

ABSTRACT:

BACKGROUND: Despite evidence of atrazine toxicity in developing organisms from experimental studies, few studies—and fewer epidemiologic investigations—have examined the potential effects of prenatal exposure.

OBJECTIVES: We assessed the association between adverse birth outcomes and urinary biomarkers of prenatal atrazine exposure, while taking into account exposures to other herbicides used on corn crops (simazine, alachlor, metolachlor, and acetochlor).

METHODS: This study used a case-cohort design nested in a prospective birth cohort conducted in the Brittany region of France from 2002 through 2006. We collected maternal urine samples to examine pesticide exposure biomarkers before the 19th week of gestation.

RESULTS: We found quantifiable levels of atrazine or atrazine mercapturate in urine samples from 5.5% of 579 pregnant women, and dealkylated and identified hydroxylated triazine metabolites in 20% and 40% of samples, respectively. The presence versus absence of quantifiable levels of atrazine or a specific atrazine metabolite was associated with fetal growth restriction [odds ratio (OR) = 1.5; 95% confidence interval (CI), 1.0–2.2] and small head circumference for sex and gestational age (OR = 1.7; 95% CI, 1.0–2.7). Associations with major congenital anomalies were not evident with atrazine or its specific metabolites. Head circumference was inversely associated with the presence of quantifiable urinary metolachlor.

CONCLUSIONS: This study is the first to assess associations of birth outcomes with multiple urinary biomarkers of exposure to triazine and chloroacetanilide herbicides. Evidence of associations with adverse birth outcomes raises particular concerns for countries where atrazine is still in use. FULL TEXT

Winchester et al., 2016

Winchester P, Proctor C, Ying J, “County-level pesticide use and risk of shortened gestation and preterm birth,” Acta Paediatrica, 2016, 105:3, DOI: 10.1111/apa.13288.

ABSTRACT:

AIM: This study assesses the association between pesticide exposure in pregnancy, preterm birth (PTB) and shortened gestation.

METHODS: Pregnancy information was abstracted from the Centers for Disease Control (CDC) Non-Public Use Natality Datasets 1990-2005. Pesticide use in maternal county of residence was calculated using California Pesticide Use Reporting (PUR) data 1990-2005. Counties were ranked by pesticide use, and birth months were sorted by peak (May-June) or nonpeak (other months) pesticide use. Multivariate logistical regression models were used.

RESULTS: Counties with higher pesticide use were associated with higher PTB (low 8.59 ± 0.11%, moderate 9.25 ± 0.07%, high 10.0 ± 0.06%, p’s < 0.001) and shorter gestations (low 39.197 ± 0.014 weeks, moderate 39.126 ± 0.011 weeks, high 39.049 ± 0.011 weeks, p’s < 0.001). Peak pesticide months were associated with higher PTB (10.01 ± 0.05% vs. 9.36 ± 0.05%, p < 0.001) and shorter gestations (39.069 ± 0.007 weeks vs. 39.122 ± 0.007 weeks, p < 0.001). The pesticide effect on shortened gestation and higher PTB was found in all racial groups. Pesticide use was highest for fungicides > insecticides > fumigants > herbicides > others. Each pesticide type was found to be associated with higher PTB and shorter gestation.

CONCLUSION: PTB and shortened gestation were significantly associated with pesticide use in maternal county of residence regardless of race, gestation at birth, and in most risk categories. FULL TEXT

Weselak et al., 2008

Weselak M, Arbuckle TE, Wigle DT, Walker MC, Krewski D, “Pre- and post-conception pesticide exposure and the risk of birth defects in an Ontario farm population.,” Reproductive Toxicology, 2008, 25:4, DOI: 10.1016/j.reprotox.2008.05.060.

ABSTRACT: The use of pesticides has enhanced the health and economies of nations around the world by improving crop production. However, pesticides may pose health risks, particularly to the fetus and young children. In a secondary analysis of the Ontario Farm Family Health Study, we explored the relationship between birth defects and parental pesticide exposure during the 3 months prior to conception and the first trimester of pregnancy. A total of 3412 pregnancies were included in the study. Logistic regression fit by maximum likelihood was used in the analysis. The results showed that pre-conception exposure to both cyanazine (odds ratio=4.99, 95% confidence interval: 1.63-15.27) and dicamba (OR=2.42, 95% CI: 1.06-5.53) were associated with increased risk of birth defects in male offspring. Nevertheless, given the self-reported nature of the exposure and outcomes in this study, the present findings should be considered primarily as hypothesis generating, requiring verification in subsequent investigations. FULL TEXT

Thongprakaisang et al., 2013

Thongprakaisang S, Thiantanawat A, Rangkadilok N, Suriyo T, Satayavivad J, “Glyphosate induces human breast cancer cells growth via estrogen receptors,” Food and Chemical Toxicology, 2013 59, DOI: 10.1016/j.fct.2013.05.057.

ABSTRACT: Glyphosate is an active ingredient of the most widely used herbicide and it is believed to be less toxic than other pesticides. However, several recent studies showed its potential adverse health effects to humans as it may be an endocrine disruptor. This study focuses on the effects of pure glyphosate on estrogen receptors (ERs) mediated transcriptional activity and their expressions. Glyphosate exerted proliferative effects only in human hormone-dependent breast cancer, T47D cells, but not in hormone-independent breast cancer, MDA-MB231 cells, at 10⁻¹² to 10⁻⁶M in estrogen withdrawal condition. The proliferative concentrations of glyphosate that induced the activation of estrogen response element (ERE) transcription activity were 5-13 fold of control in T47D-KBluc cells and this activation was inhibited by an estrogen antagonist, ICI 182780, indicating that the estrogenic activity of glyphosate was mediated via ERs. Furthermore, glyphosate also altered both ERα and β expression. These results indicated that low and environmentally relevant concentrations of glyphosate possessed estrogenic activity. Glyphosate-based herbicides are widely used for soybean cultivation, and our results also found that there was an additive estrogenic effect between glyphosate and genistein, a phytoestrogen in soybeans. However, these additive effects of glyphosate contamination in soybeans need further animal study. FULL TEXT

Skinner et al., 2013a

Skinner MK, Guerrero-Bosagna C, Haque M, Nilsson E, Bhandari R, McCarrey JR, “Environmentally induced transgenerational epigenetic reprogramming of primordial germ cells and the subsequent germ line,” PLoS One, 2013, 8:7, DOI: 10.1371/journal.pone.0066318. (Erratum in PLoS One. 2013;8(7). DOI:10.1371/annotation/7683bb48-85db-4c7e-87c0-304a7d53a587.)

ABSTRACT: A number of environmental factors (e.g. toxicants) have been shown to promote the epigenetic transgenerational inheritance of disease and phenotypic variation. Transgenerational inheritance requires the germline transmission of altered epigenetic information between generations in the absence of direct environmental exposures. The primary periods for epigenetic programming of the germ line are those associated with primordial germ cell development and subsequent fetal germline development. The current study examined the actions of an agricultural fungicide vinclozolin on gestating female (F0 generation) progeny in regards to the primordial germ cell (PGC) epigenetic reprogramming of the F3 generation (i.e. great-grandchildren). The F3 generation germline transcriptome and epigenome (DNA methylation) were altered transgenerationally. Interestingly, disruptions in DNA methylation patterns and altered transcriptomes were distinct between germ cells at the onset of gonadal sex determination at embryonic day 13 (E13) and after cord formation in the testis at embryonic day 16 (E16). A larger number of DNA methylation abnormalities (epimutations) and transcriptional alterations were observed in the E13 germ cells than in the E16 germ cells. These observations indicate that altered transgenerational epigenetic reprogramming and function of the male germline is a component of vinclozolin induced epigenetic transgenerational inheritance of disease. Insights into the molecular control of germline transmitted epigenetic inheritance are provided. FULL TEXT

Rocheleau et al., 2015

Rocheleau CM, Bertke SJ, Lawson CC, Romitti PA, Sanderson WT, Malik S, Lupo PJ, Desrosiers TA, Bell E, Druschel C, Correa A, Reefhuis J, “Maternal occupational pesticide exposure and risk of congenital heart defects in the National Birth Defects Prevention Study,” Birth Defects Research Part A, Clinical and Molecular Teratololgy, 2015, 103:10, DOI: 10.1002/bdra.23351.

ABSTRACT:

BACKGROUND: Congenital heart defects (CHDs) are common birth defects, affecting approximately 1% of live births. Pesticide exposure has been suggested as an etiologic factor for CHDs, but previous results were inconsistent.

METHODS: We examined maternal occupational exposure to fungicides, insecticides, and herbicides for 3328 infants with CHDs and 2988 unaffected control infants of employed mothers using data for 1997 through 2002 births from the National Birth Defects Prevention Study, a population-based multisite case-control study. Potential pesticide exposure from 1 month before conception through the first trimester of pregnancy was assigned by an expert-guided task-exposure matrix and job history details self-reported by mothers. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using multivariable logistic regression.

RESULTS: Maternal occupational exposure to pesticides was not associated with CHDs overall. In examining specific CHD subtypes compared with controls, some novel associations were observed with higher estimated pesticide exposure: insecticides only and secundum atrial septal defect (OR = 1.8; 95% CI, 1.3-2.7, 40 exposed cases); both insecticides and herbicides and hypoplastic left heart syndrome (OR = 5.1; 95% CI, 1.7-15.3, 4 exposed cases), as well as pulmonary valve stenosis (OR = 3.6; 95% CI, 1.3-10.1, 5 exposed cases); and insecticides, herbicides, and fungicides and tetralogy of Fallot (TOF) (OR = 2.2; 95% CI, 1.2-4.0, 13 exposed cases).

CONCLUSION: Broad pesticide exposure categories were not associated with CHDs overall, but examining specific CHD subtypes revealed some increased odds ratios. These results highlight the importance of examining specific CHDs separately. Because of multiple comparisons, additional work is needed to verify these associations. FULL TEXT

Richard et al., 2005

Richard S, Moslemi S, Sipahutar H, Benachour N, Seralini GE, “Differential effects of glyphosate and roundup on human placental cells and aromatase, ” Environmental Health Perspectives, 2005, 113:6.

ABSTRACT:

Roundup is a glyphosate-based herbicide used worldwide, including on most genetically modified plants that have been designed to tolerate it. Its residues may thus enter the food chain, and glyphosate is found as a contaminant in rivers. Some agricultural workers using glyphosate have pregnancy problems, but its mechanism of action in mammals is questioned. Here we show that glyphosate is toxic to human placental JEG3 cells within 18 hr with concentrations lower than those found with agricultural use, and this effect increases with concentration and time or in the presence of Roundup adjuvants. Surprisingly, Roundup is always more toxic than its active ingredient. We tested the effects of glyphosate and Roundup at lower nontoxic concentrations on aromatase, the enzyme responsible for estrogen synthesis. The glyphosate-based herbicide disrupts aromatase activity and mRNA levels and interacts with the active site of the purified enzyme, but the effects of glyphosate are facilitated by the Roundup formulation in microsomes or in cell culture. We conclude that endocrine and toxic effects of Roundup, not just glyphosate, can be observed in mammals. We suggest that the presence of Roundup adjuvants enhances glyphosate bioavailability and/or bioaccumulation. FULL TEXT

Rappazzo et al., 2016

Rappazzo KM, Warren JL, Meyer RE, Herring AH, Sanders AP, Brownstein NC, Luben TJ, “Maternal residential exposure to agricultural pesticides and birth defects in a 2003 to 2005 North Carolina birth cohort,” Birth Defects Research Part A, Clinical and Molecular Teratolology, 2016, 106:4, DOI: 10.1002/bdra.23479.

ABSTRACT:

BACKGROUND: Birth defects are responsible for a large proportion of disability and infant mortality. Exposure to a variety of pesticides have been linked to increased risk of birth defects.

METHODS: We conducted a case-control study to estimate the associations between a residence-based metric of agricultural pesticide exposure and birth defects. We linked singleton live birth records for 2003 to 2005 from the North Carolina (NC) State Center for Health Statistics to data from the NC Birth Defects Monitoring Program. Included women had residence at delivery inside NC and infants with gestational ages from 20 to 44 weeks (n = 304,906). Pesticide exposure was assigned using a previously constructed metric, estimating total chemical exposure (pounds of active ingredient) based on crops within 500 meters of maternal residence, specific dates of pregnancy, and chemical application dates based on the planting/harvesting dates of each crop. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals for four categories of exposure (<10(th) , 10-50(th) , 50-90(th) , and >90(th) percentiles) compared with unexposed. Models were adjusted for maternal race, age at delivery, education, marital status, and smoking status.

RESULTS: We observed elevated ORs for congenital heart defects and certain structural defects affecting the gastrointestinal, genitourinary and musculoskeletal systems (e.g., OR [95% confidence interval] [highest exposure vs. unexposed] for tracheal esophageal fistula/esophageal atresia = 1.98 [0.69, 5.66], and OR for atrial septal defects: 1.70 [1.34, 2.14]).

CONCLUSION: Our results provide some evidence of associations between residential exposure to agricultural pesticides and several birth defects phenotypes.

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