[Endocrine disruptor compounds and their role in the developmental programming of the reproductive axis].
Different perturbations during fetal and postnatal development unleash endocrine adaptations that permanently alter metabolism, increasing the susceptibility to develop later disease, process known as "developmental programming." Endocrine disruptor compounds (EDC) are widely spread in the environment and display estrogenic, anti-estrogenic or anti-androgenic activity; they are lipophilic and stored for long periods in the adipose tissue. Maternal exposure to EDC during pregnancy and lactation produces the exposure of the fetus and neonate through placenta and breast milk. Epidemiological and experimental studies have demonstrated reproductive alterations as a consequence of intrauterine and/or neonatal exposure to EDC. Diethystilbestrol (DES) is the best documented compound, this synthetic estrogen was administered to pregnant women in the 1950s and 1960s to prevent miscarriage. It was implicated in urogenital abnormalities in children exposed in utero and was withdrawn from the market. The "DES daughters" are women with high incidence of vaginal hypoplasia, spontaneous abortion, premature delivery, uterine malformation, menstrual abnormalities and low fertility. The "DES sons" show testicular dysgenesis syndrome, which is characterized by hypospadias, cryptorchidism and low semen quality. This entity is also associated wtih fetal exposure to anti-androgens as flutamide. The effects on the reproductive axis depend on the stage of development and the window of exposure, as well as the dose and the compound. The wide distribution of EDC into the environment affects both human health and ecosystems in general, the study of their mechanisms of action is extremely important currently.
Guzmán
Carolina
C
Departamento de Biologia de la Reproducción, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirin, Tlalpan, México. carova@prodigy.net.mx
Zambrano
Elena
E
D000014:Abnormalities, Drug-Induced / Q000453:epidemiology / Q000209:etiology*; D000328:Adult; D000726:Androgen Antagonists / Q000009:adverse effects / Q000494:pharmacology; D000818:Animals; D001940:Breast / Q000196:embryology; D004054:Diethylstilbestrol / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D004147:Dioxins / Q000009:adverse effects; D047108:Embryonic Development / Q000187:drug effects; D052244:Endocrine Disruptors / Q000009:adverse effects* / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000009:adverse effects / Q000494:pharmacology; D004967:Estrogens / Q000819:agonists; D005260:Female; D005262:Feminization / Q000139:chemically induced / Q000196:embryology; D005835:Genitalia / Q000002:abnormalities / Q000187:drug effects* / Q000196:embryology; D006801:Humans; D007031:Hypothalamus / Q000002:abnormalities / Q000187:drug effects / Q000196:embryology; D008297:Male; D008321:Mammary Glands, Animal / Q000196:embryology; D008895:Milk, Human / Q000737:chemistry; D010795:Phthalic Acids / Q000009:adverse effects; D048789:Phytoestrogens / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D014770:Virilism / Q000139:chemically induced / Q000196:embryology
D000726:Androgen Antagonists; D004147:Dioxins; D052244:Endocrine Disruptors; D004965:Estrogen Antagonists; D004967:Estrogens; D010795:Phthalic Acids; D048789:Phytoestrogens; C032279:phthalic acid; D004054:Diethylstilbestrol