Female Reproductive Impacts - HH-RA.org

Bibliography Tag: female reproductive impacts

Chiu, 2017

Chiu, Y. H.,”Pesticide Residues in Fruits and Vegetables: Assessment and Their Associations With Reproductive Health Outcomes;” Dissertation at Harvard Universiry, (Doctor of Science in Nutrition and Epidemiology); 2017.

ABSTRACT:

According to the Dietary Guideline, consumption of fruits and vegetables (FVs) are recommended throughout the lifespan, including during pregnancy. FVs, on the other hand, can serve as a vehicle of exposure to pesticide residues. In the US, Environmental Protection Agency (EPA) is responsible for regulating pesticides under the Federal Insecticide, Fungicide, and Rodenticide Act and the Food Quality Protection Act. While majority of the produce sampled through the US Department of Agriculture had residues below the EPA limits, there is a growing concern whether chronic exposure to these pesticide residues may have adverse health effects, especially among susceptible populations such as pregnant women. Yet, such research is scarce. This dissertation focuses on the assessment of pesticide residues in FVs and evaluates their associations with pregnancy outcomes.

We previously have developed the Pesticide Residue Burden Score (PRBS) based on selfreported diet and national surveillance data on food pesticide residues to characterize dietary exposure over the past year. In Chapter 1, we evaluated the association of the PRBS with urinary pesticide metabolites in the Environment and Reproductive Health (EARTH) Study. We found intake of high pesticide residues FVs was positively associated with urinary concentrations of pesticide biomarkers, suggesting that PRBS can characterize dietary exposure to select pesticides.

In Chapter 2, we assessed the relation between preconception intake of high and low FVs and assisted reproductive technology outcomes in EARTH study. We found that intake of high pesticide residues FVs was associated with lower probability of clinical pregnancy and live birth, while intake of low pesticide residue FVs had the opposite relations among women undergoing infertility treatment. This is the first report of such relation in humans.

In Chapter 3, we examine the association between maternal intake of high and low pesticide residue FVs with birth outcomes in a pre-birth cohort. We found that maternal intake of high pesticide residue FVs during the first trimester was associated with higher risks of small-for-gestational-age among white women, while these exposures was associated with large-for-gestational-age among nonwhite women.

In conclusion, this work demonstrated the usefulness of PRBS in assessing pesticide residue intake through FVs. Using this method, these studies suggest exposure to pesticide residues may adversely affect pregnancy and birth outcomes.

FULL TEXT

Ait-Bali et al., 2020

Ait-Bali, Y., Ba-M’hamed, S., Gambarotta, G., Sassoe-Pognetto, M., Giustetto, M., & Bennis, M.; “Pre- and postnatal exposure to glyphosate-based herbicide causes behavioral and cognitive impairments in adult mice: evidence of cortical ad hippocampal dysfunction;” Archives of Toxicology, 2020; DOI: 10.1007/s00204-020-02677-7.

ABSTRACT:

Glyphosate-based herbicides (GBH) are the most widely used pesticides worldwide. Despite considerable progress in describing the neurotoxic potential of GBH, the harmful effects on brain cytoarchitecture and behavior are still unclear. Here, we addressed the developmental impact of GBH by exposing female mice to 250 or 500 mg/kg doses of GBH during both pregnancy and lactation and then examined the downstream effects at the behavioral, neurochemical and molecular levels. We show that pre- and neonatal exposure to GBH impairs fertility and reproduction parameters as well as maternal behavior of exposed mothers. In offspring, GBH was responsible for a global delay in innate reflexes and a deficit in motor development. At the adult age, exposed animals showed a decrease of locomotor activity, sociability, learning and short- and long-term memory associated with alterations of cholinergic and dopaminergic systems. Furthermore, GBH-activated microglia and astrocytes, sign of neuroinflammation event in the medial prefrontal cortex and hippocampus. At the molecular level, a down-regulation of brain-derived neurotrophic factor (BDNF) expression and an up-regulation of tyrosine-related kinase receptor (TrkB), NR1 subunit of NMDA receptor as well as tumor necrosis factor alpha (TNFalpha) were found in the brain of GBH-exposed mice. The present work demonstrates that GBH induces numerous behavioral and cognitive abnormalities closely associated with significant histological, neurochemical and molecular impairments. It also raises fundamental concerns about the ability of current safety testing to assess risks of pesticide exposure during developmental periods of central nervous system. FULL TEXT

Guerrero Schimpf et al., 2017

Guerrero Schimpf, M., Milesi, M. M., Ingaramo, P. I., Luque, E. H., & Varayoud, J.; “Neonatal exposure to a glyphosate based herbicide alters the development of the rat uterus;” Toxicology, 2017, 376, 2-14; DOI: 10.1016/j.tox.2016.06.004.

ABSTRACT:

Glyphosate-based herbicides (GBHs) are extensively used to control weeds on both cropland and non-cropland areas. No reports are available regarding the effects of GBHs exposure on uterine development. We evaluated if neonatal exposure to a GBH affects uterine morphology, proliferation and expression of proteins that regulate uterine organogenetic differentiation in rats. Female Wistar pups received saline solution (control, C) or a commercial formulation of glyphosate (GBH, 2mg/kg) by sc injection every 48h from postnatal day (PND) 1 to PND7. Rats were sacrificed on PND8 (neonatal period) and PND21 (prepubertal period) to evaluate acute and short-term effects, respectively. The uterine morphology was evaluated in hematoxylin and eosin stained sections. The epithelial and stromal immunophenotypes were established by assessing the expression of luminal epithelial protein (cytokeratin 8; CK8), basal epithelial proteins (p63 and pan cytokeratin CK1, 5, 10 and 14); and vimentin by immunohistochemistry (IHC). To investigate changes on proteins that regulate uterine organogenetic differentiation we evaluated the expression of estrogen receptor alpha (ERalpha), progesterone receptor (PR), Hoxa10 and Wnt7a by IHC. The GBH-exposed uteri showed morphological changes, characterized by an increase in the incidence of luminal epithelial hyperplasia (LEH) and an increase in the stromal and myometrial thickness. The epithelial cells showed a positive immunostaining for CK8, while the stromal cells for vimentin. GBH treatment increased cell proliferation in the luminal and stromal compartment on PND8, without changes on PND21. GBH treatment also altered the expression of proteins involved in uterine organogenetic differentiation. PR and Hoxa10 were deregulated both immediately and two weeks after the exposure. ERalpha was induced in the stromal compartment on PND8, and was downregulated in the luminal epithelial cells of gyphosate-exposed animals on PND21. GBH treatment also increased the expression of Wnt7a in the stromal and glandular epithelial cells on PND21. Neonatal exposure to GBH disrupts the postnatal uterine development at the neonatal and prepubertal period. All these changes may alter the functional differentiation of the uterus, affecting the female fertility and/or promoting the development of neoplasias. FULL TEXT

Zanardi et al., 2020

Zanardi, M. V., Schimpf, M. G., Gastiazoro, M. P., Milesi, M. M., Munoz-de-Toro, M., Varayoud, J., & Durando, M.; “Glyphosate-based herbicide induces hyperplastic ducts in the mammary gland of aging Wistar rats;” Molecular and Cellular Endocrinology, 2019, 501, 110658; DOI: 10.1016/j.mce.2019.110658.

ABSTRACT:

Glyphosate-based herbicide (GBH) exposure is known to have adverse effects on endocrine-related tissues. Here, we aimed to determine whether early postnatal exposure to a GBH induces long-term effects on the rat mammary gland. Thus, female Wistar pups were injected with saline solution (Control) or GBH (2 mg glyphosate/kg/day) on postnatal days (PND) 1, 3, 5 and 7. At 20 months of age, mammary gland samples were collected to determine histomorphological features, proliferation index and the expression of steroid hormone receptors expression, by immunohistochemistry, and serum samples were collected to assess 17beta-estradiol (E2) and progesterone (P4) levels. GBH exposure induced morphological changes evidenced by a higher percentage of hyperplastic ducts and a fibroblastic-like stroma in the mammary gland. GBH-treated rats also showed a high expression of steroid hormone receptors in hyperplastic ducts. The results indicate that early postnatal exposure to GBH induces long-term alterations in the mammary gland morphology of aging female rats. FULL TEXT

Chiu et al., 2018

Chiu, Y. H., Williams, P. L., Gillman, M. W., Gaskins, A. J., Minguez-Alarcon, L., Souter, I., Toth, T. L., Ford, J. B., Hauser, R., Chavarro, J. E., & Team, Earth Study; “Association Between Pesticide Residue Intake From Consumption of Fruits and Vegetables and Pregnancy Outcomes Among Women Undergoing Infertility Treatment With Assisted Reproductive Technology;” JAMA Internal Medicine, 2018, 178(1), 17-26; DOI: 10.1001/jamainternmed.2017.5038.

ABSTRACT:

IMPORTANCE:

Animal experiments suggest that ingestion of pesticide mixtures at environmentally relevant concentrations decreases the number of live-born offspring. Whether the same is true in humans is unknown. Objective: To examine the association of preconception intake of pesticide residues in fruits and vegetables (FVs) with outcomes of infertility treatment with assisted reproductive technologies (ART).

DESIGNT, SETTING, AND PARTICIPANTS:

This analysis included 325 women who completed a diet assessment and subsequently underwent 541 ART cycles in the Environment and Reproductive Health (EARTH) prospective cohort study (2007-2016) at a fertility center at a teaching hospital. We categorized FVs as having high or low pesticide residues using a validated method based on surveillance data from the US Department of Agriculture. Cluster-weighted generalized estimating equations were used to analyze associations of high- and low-pesticide residue FV intake with ART outcomes.

MAIN OUTCOMES AND MEASURES:

Adjusted probabilities of clinical pregnancy and live birth per treatment cycle.

RESULTS:

In the 325 participants (mean [SD] age, 35.1 [4.0] y; body mass index, 24.1 [4.3]), mean (SD) intakes of high- and low-pesticide residue FVs were 1.7 (1.0) and 2.8 (1.6) servings/d, respectively. Greater intake of high-pesticide residue FVs was associated with a lower probability of clinical pregnancy and live birth. Compared with women in the lowest quartile of high-pesticide FV intake (<1.0 servings/d), women in the highest quartile (>/=2.3 servings/d) had 18% (95% CI, 5%-30%) lower probability of clinical pregnancy and 26% (95% CI, 13%-37%) lower probability of live birth. Intake of low-pesticide residue FVs was not significantly related to ART outcomes.

CONCLUSIONS AND RELEVANCE:

Higher consumption of high-pesticide residue FVs was associated with lower probabilities of pregnancy and live birth following infertility treatment with ART. These data suggest that dietary pesticide exposure within the range of typical human exposure may be associated with adverse reproductive consequences. FULL TEXT

International Federation of Gynecology and Obstetrics, 2019

International Federation of Gynecology and Obstetrics; “Removal of glyphosate from global usage: A Statement by the FIGO Reproductive and Developmental Environmental Health Committee,” Available at: https://www.figo.org/statement-glyphosate-removal, Date posted: 07/31/2019, Date accessed: 8/6/2019.

SUMMARY:

The International Federation of Gynecology and Obstetrics (FIGO), a professional group that advocates for OB/GYN groups around the world. They work with the World Health Organization and United Nations to consult on women and children’s health and wellness issues, recommends that all glyphosate use be phased out due to “the recognised impact on the health and well-being of women and newborn children worldwide.”

FIGO points out the conflicting opinions about the safety of glyphosate, as evidenced by the EPA and IARC’s diametric designations as “non-carcinogenic” and “probably carcinogenic,” respectively. But, they argue, given that the most recent meta-analysis from February 2019 found “a compelling link between non-Hodgkins lymphoma and glyphosate,” and rodent studies have demonstrated the potential for transgenerational epigenetic changes, FIGO urges governments to apply the precautionary principal and prioritize “establishing safety, now and across generations, prior to exposure to chemical products.” They conclude: “We recommend that glyphosate exposure to populations should end with a full global phase out.” FULL TEXT

Ford and Schust, 2009

Ford, Holly B., & Schust, Danny J.; “Recurrent pregnancy loss: etiology, diagnosis, and therapy;” Reviews in Obstetrics & Gynecology, 2009, 2(2), 76-83.

ABSTRACT:

Spontaneous pregnancy loss is a surprisingly common occurrence, with approximately 15% of all clinically recognized pregnancies resulting in pregnancy failure. Recurrent pregnancy loss (RPL) has been inconsistently defined. When defined as 3 consecutive pregnancy losses prior to 20 weeks from the last menstrual period, it affects approximately 1% to 2% of women. This review highlights the current understanding of the various etiologies implicated in RPL, including factors known to be causative, as well as those implicated as possible causative agents. The appropriate diagnostic evaluation, therapy, and prognosis are also addressed. FULL TEXT

Perego et al., 2017

Perego, Maria Chiara, Caloni, Francesca, Cortinovis, Cristina, Schutz, Luis F., Albonico, Marco, Tsuzukibashi, Denise, & Spicer, Leon J., “Influence of a Roundup formulation on glyphosate effects on steroidogenesis and proliferation of bovine granulosa cells in vitro,” Chemosphere, 2017, 188, 274-279. DOI: 10.1016/j.chemosphere.2017.09.007.

ABSTRACT:

Glyphosate (N-phosphonomethyl-glycine) is a non-selective systemic herbicide widely used worldwide. The purpose of this study is to determine if glyphosate alone (GLPH) or in formulation with Roundup (G-RU) can affect granulosa cell proliferation and steroid production. Four experiments were conducted. In Exp. 1, 10 and 300 μg/mL of GLPH had no effect (P > 0.05) on cell numbers, estradiol or progesterone production, whereas 10 and 300 μg/mL of G-RU dramatically decreased (P < 0.05) cell numbers and estradiol and progesterone production. In Exp. 2, G-RU at 0.1 μg/mL had no significant effect whereas G-RU at 10 μg/mL decreased (P < 0.05) GC numbers, progesterone and estradiol production. In the absence of IGF1 but presence of FSH, 1 μg/mL of G-RU decreased (P < 0.05) estradiol production, whereas in the presence of IGF1 and FSH, 1 μg/mL of G-RU increased (P < 0.05) cell numbers, progesterone and estradiol production. In Exp. 3, IGF1 significantly increased cell numbers (by 2.8-fold) and estradiol (by 17.8-fold) and progesterone (by 6.1-fold) production. GLPH at 10 μg/mL alone had no significant effect on FSH-induced (i.e., basal) or FSH plus IGF1-induced cell numbers, estradiol or progesterone production. However, G-RU at 10 μg/mL significantly inhibited FSH plus IGF1-induced cell numbers, estradiol and progesterone production by 65%–91%. In Exp. 4, 48 h treatment of G-RU had no significant effect on viability of attached cells. In conclusion, the present studies demonstrate that GLPH and particularly G-RU may have the potential to impair reproductive function in cattle.

Lang and Nuevo-Chiquero, 2012

Lang, K., & Nuevo-Chiquero, A., “Trends in self-reported spontaneous abortions: 1970-2000,” Demography, 2012, 49(3), 989-1009. DOI: 10.1007/s13524-012-0113-0.

ABSTRACT:

Little is known about how the miscarriage rate has changed over the past few decades in the United States. Data from Cycles IV to VI of the National Survey of Family Growth (NSFG) were used to examine trends from 1970 to 2000. After accounting for abortion availability and the characteristics of pregnant women, the rate of reported miscarriages increased by about 1.0% per year. This upward trend is strongest in the first seven weeks and absent after 12 weeks of pregnancy. African American and Hispanic women report lower rates of early miscarriage than do whites. The probability of reporting a miscarriage rises by about 5% per year of completed schooling. The upward trend, especially in early miscarriages, suggests awareness of pregnancy rather than prenatal care to be a key factor in explaining the evolution of self-reported miscarriages. Any beneficial effects of prenatal care on early miscarriage are obscured by this factor. Differences in adoption of early-awareness technology, such as home pregnancy tests, should be taken into account when analyzing results from self-reports or clinical trials relying on awareness of pregnancy in its early weeks. FULL TEXT

Ingaramo et al., 2016

Ingaramo, P. I., Varayoud, J., Milesi, M. M., Schimpf, M. G., Munoz-de-Toro, M., & Luque, E. H., “Effects of neonatal exposure to a glyphosate-based herbicide on female rat reproduction,” Reproduction, 2016, 152(5), 403-415. DOI: 10.1530/REP-16-0171.

ABSTRACT:

In this study, we investigated whether neonatal exposure to a glyphosate-based herbicide (GBH) alters the reproductive performance and the molecular mechanisms involved in the decidualization process in adult rats. Newborn female rats received vehicle or 2 mg/kg/day of a GBH on postnatal days (PND) 1, 3, 5 and 7. On PND90, the rats were mated to evaluate (i) the reproductive performance on gestational day (GD) 19 and (ii) the ovarian steroid levels, uterine morphology, endometrial cell proliferation, apoptosis and cell cycle regulators, and endocrine pathways that regulate uterine decidualization (steroid receptors/COUP-TFII/Bmp2/Hoxa10) at the implantation sites (IS) on GD9. The GBH-exposed group showed a significant increase in the number of resorption sites on GD19, associated with an altered decidualization response. In fact, on GD9, the GBH-treated rats showed morphological changes at the IS, associated with a decreased expression of estrogen and progesterone receptors, a downregulation of COUP-TFII (Nr2f2) and Bmp2 mRNA and an increased expression of HOXA10 and the proliferation marker Ki67(Mki67) at the IS. We concluded that alterations in endometrial decidualization might be the mechanism of GBH-induced post-implantation embryo loss. FULL TEXT

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