Gender and sex differences in phthalate-induced toxicity in the reproductive system
Gender and sex differences in phthalate-induced toxicity in the reproductive system
批准号:
10389709
负责人:
Indrani C Bagchi
金额:
$5.46万
依托单位国家:
美国
项目类别:
财政年份:
2020
资助国家:
美国
项目状态:
已结题
起止时间:
2020-08-17 至 2024-05-31
关键词:
Adult ChildrenAffectAgeAge-MonthsAndrogensAreaBehaviorBehavioralBiochemicalBirthBrainBrain regionChemical ExposureChemicalsChildComplexCosmeticsDataDevelopmentDiethylhexyl PhthalateDiseaseDoseEnvironmentEstradiolEstrogensExposure toFemaleFeminineFertilityFollicle Stimulating HormoneFunctional disorderGenderGonadal structureHealthHormone ReceptorHormonesHypothalamic structureLH ReceptorsLeadLifeLubricantsLuteinizing HormoneMasculineMeasuresMedical DeviceMolecularMorphologyMusOvaryParentsPartner in relationshipPathway interactionsPerformancePituitary GlandPlasticizersPregnancyPregnant WomenProductionProgesteroneReportingReproductive BehaviorReproductive HealthReproductive systemSex BehaviorSex DifferencesSolventsSperm Count ProcedureTestingTestisTestosteroneTimeLineTissuesToxic effectToyUterusWomanWomen&aposs Healthbaseconsumer productexperimental studygender behaviorgender differenceimprovedinterestmalemating behaviormennoveloffspringpersonal care productsphthalatespreferencepregnantprenatalprenatal exposurereproductivereproductive functionreproductive hormonereproductive organreproductive outcomereproductive toxicitysexsexual dimorphismsubfertilitytime-to-pregnancyyoung adult
中文摘要
邻苯二甲酸酯是一种无处不在的合成化学品,在无数消费者中用作增塑剂和稳定剂。
产品。人们每天无处不在地接触邻苯二甲酸酯,而且根据性别和性别的不同
在邻苯二甲酸盐暴露和毒性方面存在差异。然而,很少有研究考察性别--以及
出生前接触邻苯二甲酸盐对后代生殖健康的性别影响。这个
生殖系统是复杂的,需要一个正常发育和功能的时间表
生殖组织(即脑、脑垂体、卵巢、睾丸和子宫)、关键生殖激素(即,
雌激素、雄激素、黄体酮、黄体生成素和卵泡刺激素)和生殖
性行为(即男性和女性的性兴趣、行为反应和伴侣偏好),
这可能会因性别和性别而不同。因此,父母的研究检验了接触到一种
与环境相关的邻苯二甲酸酯混合物导致雌性后代比雄性后代更早不孕
通过涉及性别和性别特异性对大脑、脑下垂体、性腺、子宫、关键
荷尔蒙途径和生殖行为。为了验证这一假设,家长研究将确定:
1)出生前接触与环境相关的邻苯二甲酸盐混合物对KEY形态的影响
生殖组织,2)产前暴露于与环境相关的邻苯二甲酸盐混合物对
激素的产生和反应性,以及3)产前暴露在环境中的影响
相关邻苯二甲酸盐混合物对生殖行为和性吸引力的影响。总而言之,父代
研究将确定产前邻苯二甲酸盐暴露导致性别差异和性别差异的机制。
在后代中特定的亚生育和生殖行为。更好地理解这些机制
邻苯二甲酸盐的作用可能导致开发治疗邻苯二甲酸盐诱导的新靶点
疾病。它还可能导致确定导致特定性别和特定性别不利的因素
生殖结果。这可能对改善女性和男性的健康产生重大影响,
特别是因为目前还不可能消除邻苯二甲酸盐的接触。
英文摘要
Phthalates are ubiquitous synthetic chemicals used as plasticizers and stabilizers in a myriad of consumer
products. People are ubiquitously exposed to phthalates on a daily basis, and gender- and sex-specific
differences exist in phthalate exposures and toxicity. However, few studies have examined the gender- and
sex-specific effects of prenatal exposure to phthalates on the reproductive health of the offspring. The
reproductive system is complex and requires a timeline of normal development and function of the
reproductive tissues (i.e., brain, pituitary, ovary, testes, and uterus), key reproductive hormones (i.e.,
estrogens, androgens, progesterone, luteinizing hormone, and follicle-stimulating hormone), and reproductive
sex behaviors (i.e., male and female sexual interest, behavioral responsiveness, and partner preference),
which may differ by gender and sex. Therefore, the parent studies test the hypothesis that exposure to an
environmentally relevant phthalate mixture causes earlier subfertility in female offspring than male offspring
through mechanisms that involve gender- and sex-specific effects on the brain, pituitary, gonads, uterus, key
hormone pathways, and reproductive behaviors. To test this hypothesis, the parent studies will determine:
1) the effects of prenatal exposure to an environmentally relevant phthalate mixture on the morphology of key
reproductive tissues, 2) the effects of prenatal exposure to an environmentally relevant phthalate mixture on
hormone production and responsiveness, and 3) the impact of prenatal exposure to an environmentally
relevant phthalate mixture on reproductive behaviors and sexual attractiveness. Collectively, the parent
studies will determine the mechanisms by which prenatal phthalate exposure causes sex-specific and gender-
specific subfertility and reproductive behavior in the offspring. A better understanding of the mechanisms of
action of phthalates may lead to the development of novel targets for the treatment of phthalate-induced
diseases. It also may lead to the identification of factors that cause sex-specific and gender-specific adverse
reproductive outcomes. This could have a major impact on improving the health of women and men,
particularly because it currently is not possible to eliminate phthalate exposure.
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