Abstract
Endocrine-disrupting chemicals are known to interfere with normal reproductive function and hormone signaling. Phthalates, bisphenol A, pesticides, and environmental contaminants such as ...polychlorinated biphenyls and dioxins are known endocrine-disrupting chemicals that have been shown to negatively affect both male and female reproduction. Exposure to these chemicals occurs on a daily basis owing to these compounds being found in plastics, personal care products, and pesticides. Recently, studies have shown that these chemicals may cause transgenerational effects on reproduction in both males and females. This is of concern because exposure to these chemicals prenatally or during adult life can negatively impact the reproductive health of future generations. This mini-review summarizes the endocrine-disrupting chemicals that humans are exposed to on a daily basis and what is known about the transgenerational effects that these chemicals may have on male and female reproduction.
We summarized the scientific literature published from 2007 to 2016 on the potential effects of bisphenol A (BPA) on female fertility. We focused on overall fertility outcomes (e.g., ability to ...become pregnant, number of offspring), organs that are important for female reproduction (i.e., oviduct, uterus, ovary, hypothalamus, and pituitary), and reproductive-related processes (i.e., estrous cyclicity, implantation, and hormonal secretion). The reviewed literature indicates that BPA may be associated with infertility in women. Potential explanations for this association can be generated from experimental studies. Specifically, BPA may alter overall female reproductive capacity by affecting the morphology and function of the oviduct, uterus, ovary, and hypothalamus-pituitary-ovarian axis in animal models. In addition, BPA may disrupt estrous cyclicity and implantation. Nevertheless, further studies are needed to better understand the exact mechanisms of action and to detect potential reproductive toxicity at earlier stages.
Humans and animals are repeatedly exposed to endocrine disruptors, many of which are ubiquitous in the environment. Endocrine disruptors interfere with hormone action; thus, causing non-monotonic ...dose responses that are atypical of standard toxicant exposures. The female reproductive system is particularly susceptible to the effects of endocrine disruptors. Likewise, exposures to endocrine disruptors during developmental periods are particularly concerning because programming during development can be adversely impacted by hormone level changes. Subsequently, developing reproductive tissues can be predisposed to diseases in adulthood and these diseases can be passed down to future generations. The mechanisms of action by which endocrine disruptors cause disease transmission to future generations are thought to include epigenetic modifications. This review highlights the effects of endocrine disruptors on the female reproductive system, with an emphasis on the multi- and transgenerational epigenetic effects of these exposures. Summary Sentence Endocrine disruptors alter reproductive tissues and functions across generations via epigenetic mechanisms.
Anthropogenic contaminants in water can impose risks to reproductive health. Most of these compounds are known to be endocrine disrupting chemicals (EDCs). EDCs can impact the endocrine system and ...subsequently impair the development and fertility of non-human animals and humans. The source of chemical contamination in water is diverse, originating from byproducts formed during water disinfection processes, release from industry and livestock activity, or therapeutic drugs released into sewage. This review discusses the occurrence of EDCs in water such as disinfection byproducts, fluorinated compounds, bisphenol A, phthalates, pesticides, and estrogens, and it outlines their adverse reproductive effects in non-human animals and humans.
Phthalates are used in a large variety of products, such as building materials, medical devices, and personal care products. Most previous studies on the toxicity of phthalates have focused on single ...phthalates, but it is also important to study the effects of phthalate mixtures because humans are exposed to phthalate mixtures. Thus, we tested the hypothesis that prenatal exposure to an environmentally relevant phthalate mixture adversely affects female reproduction in mice. To test this hypothesis, pregnant CD-1 dams were orally dosed with vehicle (tocopherol-stripped corn oil) or a phthalate mixture (20 and 200μg/kg/day, 200 and 500mg/kg/day) daily from gestational day 10 to birth. The mixture was based on the composition of phthalates detected in urine samples from pregnant women in Illinois. The mixture included 35% diethyl phthalate, 21% di(2-ethylhexyl) phthalate, 15% dibutyl phthalate, 15% diisononyl phthalate, 8% diisobutyl phthalate, and 5% benzylbutyl phthalate. Female mice born to the exposed dams were subjected to tissue collections and fertility tests at different ages. Our results indicate that prenatal exposure to the phthalate mixture significantly increased uterine weight and decreased anogenital distance on postnatal days 8 and 60, induced cystic ovaries at 13months, disrupted estrous cyclicity, reduced fertility-related indices, and caused some breeding complications at 3, 6, and 9months of age. Collectively, our data suggest that prenatal exposure to an environmentally relevant phthalate mixture disrupts aspects of female reproduction in mice.
•Prenatal exposure to a phthalate mixture disrupts F1 estrous cyclicity.•Prenatal exposure to a phthalate mixture induces F1 ovarian cysts.•Prenatal exposure to a phthalate mixture decreases F1 female fertility-related indices.•Prenatal exposure to a phthalate mixture induces F1 breeding complications.
Abstract
Phthalates are used in consumer products and are known endocrine-disrupting chemicals. However, limited information is available on the effects of phthalate mixtures on female reproduction. ...Previously, we developed a phthalate mixture made of 35% diethyl phthalate, 21% di(2-ethylhexyl) phthalate, 15% dibutyl phthalate, 15% di-isononyl phthalate, 8% di-isobutyl phthalate, and 5% benzylbutyl phthalate that mimics human exposure. We tested the effects of prenatal exposure to this mixture on reproductive outcomes in first-filial-generation (F1) female mice and found that it impaired reproductive outcomes. However, the impact of this exposure on second-filial-generation (F2) and third-filial-generation (F3) females was unknown. Thus, we hypothesized that prenatal exposure to the phthalate mixture induces multigenerational and transgenerational effects on female reproduction. Pregnant CD-1 dams were orally dosed with vehicle (tocopherol-stripped corn oil) or a phthalate mixture (20 and 200 µg/kg/d, 200 and 500 mg/kg/d) daily from gestational day 10 to birth. Adult F1 females born to these dams were used to generate the F2 generation and adult F2 females born to F1 females were used to generate the F3 generation. F2 and F3 females were subjected to tissue collections and fertility tests. Prenatal phthalate mixture exposure increased uterine weight, anogenital distance, and body weight; induced cystic ovaries; and caused fertility complications in the F2 generation. It also increased uterine weight, decreased anogenital distance, and caused fertility complications in the F3 generation. These data suggest that prenatal exposure to the phthalate mixture induces multigenerational and transgenerational effects on female reproduction.
This study shows that prenatal exposure to the phthalate mixture induces multigenerational and transgenerational effects on female reproduction.
Abstract
Di(2-ethylhexyl) phthalate (DEHP) is a plasticizer used in a variety of consumer products. This is concerning because DEHP is an endocrine disruptor and ovarian toxicant. Diisononyl ...phthalate (DiNP) is a DEHP replacement that is a rising human toxicant due to its increased use as a DEHP substitute. However, little is known about the effects of DEHP or DiNP exposure during adulthood on female reproduction. Thus, this study tested the hypothesis that DEHP or DiNP exposure during adulthood has long-term consequences for female reproduction in mice. Adult female CD-1 mice (39–40 days) were orally dosed with vehicle control (corn oil), DEHP (20 µg/kg/day–200 mg/kg/day), or DiNP (20 µg/kg/day–200 mg/kg/day) for 10 days. Females were paired with untreated male mice for breeding trials immediately post-dosing and again at 3 and 9 months post-dosing. Immediately post-dosing, DEHP and DiNP did not affect fertility. At 3 months post-dosing, DiNP (20 and 100 µg/kg/day and 200 mg/kg/day) significantly disrupted estrous cyclicity, and DiNP and DEHP (20 µg/kg/day) significantly reduced the ability of females to get pregnant. At 9 months post-dosing, DiNP significantly disrupted estrous cyclicity (100 µg/kg/day), reduced time to mating (100 µg/kg/day–200 mg/kg/day), and borderline reduced percent of females who produced offspring (20 mg/kg/day). At 9 months post-dosing, DEHP (200 µg/kg/day and 200 mg/kg/day) and DiNP (100 µg/kg/day and 20 and 200 mg/kg/day) increased numbers of male-biased litters. These data show that DEHP and DiNP exposure has long-term consequences for female reproduction, even long after cessation of exposure.
Endocrine disrupting chemicals are ubiquitous chemicals that exhibit endocrine disrupting properties in both humans and animals. Female reproduction is an important process, which is regulated by ...hormones and is susceptible to the effects of exposure to endocrine disrupting chemicals. Disruptions in female reproductive functions by endocrine disrupting chemicals may result in subfertility, infertility, improper hormone production, estrous and menstrual cycle abnormalities, anovulation, and early reproductive senescence. This review summarizes the effects of a variety of synthetic endocrine disrupting chemicals on fertility during adult life. The chemicals covered in this review are pesticides (organochlorines, organophosphates, carbamates, pyrethroids, and triazines), heavy metals (arsenic, lead, and mercury), diethylstilbesterol, plasticizer alternatives (di-(2-ethylhexyl) phthalate and bisphenol A alternatives), 2,3,7,8-tetrachlorodibenzo-p-dioxin, nonylphenol, polychlorinated biphenyls, triclosan, and parabens. This review focuses on the hypothalamus, pituitary, ovary, and uterus because together they regulate normal female fertility and the onset of reproductive senescence. The literature shows that several endocrine disrupting chemicals have endocrine disrupting abilities in females during adult life, causing fertility abnormalities in both humans and animals.
Abstract
Di(2-ethylhexyl) phthalate (DEHP) is a plasticizer in many consumer products. Although DEHP is a known endocrine disruptor, little is known about the effects of DEHP exposure on female ...reproduction. Thus, this study tested the hypothesis that prenatal DEHP exposure affects follicle numbers, estrous cyclicity, and hormone levels in multiple generations of mice. Pregnant CD-1 mice were orally dosed with corn oil (vehicle control) or DEHP (20 and 200 µg/kg/d and 500 and 750 mg/kg/d) from gestational day 11 until birth. The F1 females were mated with untreated males to create the F2 generation, and the F2 females were mated with untreated males to create the F3 generation. At 1 year, ovaries, hormones, and estrous cycles were analyzed in each generation. Prenatal DEHP exposure altered estrous cyclicity (750 mg/kg/d), increased the presence of ovarian cysts (750 mg/kg/d), and decreased total follicle numbers (750 mg/kg/d) in the F1 generation. It also decreased anogenital distance (200 µg/kg/d) and altered follicle numbers (200 µg/kg/d and 500 mg/kg/d) in the F2 generation, and it altered estrous cyclicity (20 and 200 µg/kg/d and 500 and 750 mg/kg/d) and decreased folliculogenesis (200 µg/kg/d and 500 mg/kg/d) in the F3 generation. Further, prenatal DEHP increased estradiol levels (F1 and F3), decreased testosterone levels (F1, F2, and F3), decreased progesterone levels (F2), altered gonadotropin hormone levels (F1 and F3), and decreased inhibin B levels (F1 and F3). Collectively, these data show that prenatal exposure to DEHP has multigenerational and transgenerational effects on female reproduction and it may accelerate reproductive aging.
This study shows that prenatal exposure to di(2-ethylhexyl) phthalate causes long-term transgenerational effects on female reproduction and may accelerate reproductive aging.
Phthalates are used in building materials, medical devices, and personal care products. Most studies on phthalates have focused on single phthalates, but it is important to study mixtures of ...phthalates because humans are exposed to such mixtures daily. We tested the hypothesis that phthalate mixture exposure decreases antral follicle growth, compromises steroidogenic capacity, and induces atresia. Antral follicles from adult CD-1 mice were cultured with vehicle control or phthalate mixture (1-500 µg/ml) for 96 h. The mixture was made of 35% diethyl phthalate, 21% di(2-ethylhexyl) phthalate, 15% dibutyl phthalate, 15% diisononyl phthalate, 8% diisobutyl phthalate, and 5% benzylbutyl phthalate. During culture, antral follicle diameters were measured every 24 h to monitor growth. After culture, media were subjected to measurements of sex steroid hormones and follicles were subjected to evaluation of gene expression and atresia. The phthalate mixture (100 and 500 µg/ml) decreased antral follicle growth starting at 24 h compared to controls. The mixture at 10, 100, and 500 µg/ml also decreased androstenedione, testosterone, estrone, and estradiol levels compared to control. The mixture (10, 100, and 500 µg/ml) reduced atresia rating, but it induced more oocyte fragmentation compared to control. The phthalate mixture at different doses adversely affected cell cycle regulators, antioxidant enzymes, apoptotic factors, steroidogenic enzymes, and receptors. Collectively, these data indicate that exposure to an environmentally relevant phthalate mixture reduces antral follicle growth, induces oocyte fragmentation, and decreases hormone production by adversely affecting the expression of cell cycle regulators, apoptotic factors, steroidogenic enzymes, and receptors.
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