Gender and sex differences in phthalate-induced toxicity in the reproductive system

邻苯二甲酸盐引起的生殖系统毒性的性别和性别差异

• 批准号: 10619165
• 负责人: Indrani C Bagchi
• 金额: $ 6.47万
• 依托单位: UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-17 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10619165
• 关键词: Adult Children; Affect; Age; Age-Months; Androgens; Area; Behavior; Behavioral; Biochemical; Birth; Brain; Brain region; Chemical Exposure; Chemicals; Child; Complex; Cosmetics; Data; Development; Diethylhexyl Phthalate; Disease; Dose; Environment; Estradiol; Estrogens; Exposure to; Female; Feminine; Fertility; Follicle Stimulating Hormone; Functional disorder; Gender; Gonadal structure; Health; Hormone Receptor; Hormones; Hypothalamic structure; LH Receptors; Lead; Life; Lubricants; Luteinizing Hormone; Masculine; Measures; Medical Device; Molecular; Morphology; Mus; Ovary; Partner in relationship; Pathway interactions; Performance; Persons; Pituitary Gland; Plasticizers; Pregnancy; Pregnant Women; Production; Progesterone; Reporting; Reproductive Behavior; Reproductive Health; Reproductive system; Sex Behavior; Sex Differences; Solvents; Sperm Count Procedure; Testing; Testis; Testosterone; TimeLine; Tissues; Toxic effect; Toy; Uterus; Woman; Women' s Health; Work; base; consumer product; experimental study; gender behavior; gender difference; improved; interest; male; mating behavior; men; novel; offspring; personal care products; phthalates; preference; pregnant; prenatal; prenatal exposure; reproductive; reproductive function; reproductive hormone; reproductive organ; reproductive outcome; reproductive toxicity; sex; sexual dimorphism; subfertility; time-to-pregnancy; young adult

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 proposed studies will 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 proposed 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 proposed work 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.

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，拟议的研究将检验暴露于 一种与环境相关的邻苯二甲酸酯混合物导致女性后代比男性更早不孕 通过涉及性别和性别对大脑、脑下垂体、性腺的特定影响的机制， 子宫、关键荷尔蒙途径和生殖行为。为了验证这一假设，拟议中的研究 将确定：1)产前暴露于与环境相关的邻苯二甲酸盐混合物对 关键生殖组织的形态，2)产前暴露于与环境有关的 邻苯二甲酸盐混合物对激素产生和反应性的影响，以及3)产前接触An的影响。 与环境相关的邻苯二甲酸酯混合物对生殖行为和性吸引力的影响。总而言之， 这项拟议的工作将确定产前邻苯二甲酸盐暴露导致性别差异的机制。 以及特定性别的亚生育能力和后代的生殖行为。更好地理解 邻苯二甲酸酯的作用机制可能导致开发治疗糖尿病的新靶点 邻苯二甲酸盐引起的疾病。它还可能导致识别导致特定性别和 因性别而异的不良生殖后果。这可能会对改善健康状况产生重大影响 女性和男性，特别是因为目前还不可能消除邻苯二甲酸盐的接触。