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: 10240715
• 负责人: Indrani C Bagchi
• 金额: $ 51.94万
• 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/10240715
• 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; 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.

邻苯二甲酸酯是普遍存在的合成化学品，在无数消费品中用作增塑剂和稳定剂。 产品.人们每天都在无处不在地接触邻苯二甲酸酯， 邻苯二甲酸酯暴露和毒性存在差异。然而，很少有研究考察了性别-和 产前暴露于邻苯二甲酸酯对后代生殖健康的性别特异性影响。的 生殖系统是复杂的，需要一个正常发育和功能的时间轴， 生殖组织（即，脑、垂体、卵巢、睾丸和子宫），关键生殖激素（即， 雌激素、雄激素、孕酮、促黄体激素和促卵泡激素），以及生殖 性行为（即，男性和女性的性兴趣、行为反应和伴侣偏好）， 这可能因性别和性别而异。因此，拟议的研究将检验以下假设： 与环境相关的邻苯二甲酸酯混合物会导致雌性后代比雄性后代更早出现生育力低下 通过对大脑、脑垂体、性腺 子宫、关键激素途径和生殖行为。为了验证这一假设，拟议的研究 将确定：1）产前暴露于环境相关的邻苯二甲酸酯混合物对 关键生殖组织的形态，2）产前暴露于环境相关的影响， 邻苯二甲酸酯混合物对激素产生和反应性的影响，以及3）产前暴露于 环境相关的邻苯二甲酸酯混合物对生殖行为和性吸引力。总的来说， 拟议的工作将确定产前邻苯二甲酸酯暴露引起性别特异性 以及后代的性别特异性低生育力和生殖行为。更好地理解 邻苯二甲酸酯的作用机制可能会导致新的治疗目标的发展， 邻苯二甲酸酯引起的疾病。它也可能导致确定的因素，造成性别特异性和 针对不同性别的不良生殖结果。这可能对改善儿童的健康产生重大影响。 女性和男性，特别是因为目前不可能消除邻苯二甲酸酯暴露。