Endokrin Bozucuların Üreme Sistemi Üzerindeki Etkileri

Abstract

Endocrine Disrupting Chemicals are defined as “an exogenous chemical, or a mixture of chemicals, that can interfere with any aspect of hormone action”. Endocrine disruptors consist of pesticides, fungicides, industrial chemicals, plasticizers, and phytoestrogens. Time exposure to endocrine disruptors is an important issue. The developing fetus and neonates are more vulnerable in terms of endocrine disruption. Endocrine disruptors may interfere with the synthesis, action, and metabolism of sex steroid hormones. They can cause developmental and fertility problems, infertility, and hormone-sensitive cancers in women and men. Estrogen and androgen pathways are important in gonadal development, the determination of secondary sex characteristics, and gametogenesis. Endocrine disruptors mediate their action through respective receptors and/or downstream signaling. Endocrine disruptors can cause antagonistic or agonistic responses, acting through estrogen/androgen receptors. Bisphenol-A (BPA), dichlorodiphenyltrichloroethane, dichlorodiphenyldichloroethylene, polychlorinated biphenyls, and phthalates are major endocrine disruptors that interfere with the normal estrogen/androgen pathways leading to infertility in both sexes through DNA damage in spermatozoids, altered methylation pattern, histone modifications and miRNA expression. Endocrine disruptors affect the increasing incidence of male reproductive disorders, including poor semen quality, testicular malignancies, and congenital developmental defects such as hypospadias and cryptorchidism. Bisphenol-A (BPA) has also been reported to be associated with female infertility. BPA can cause dysregulation of the hypothalamic-pituitary-ovarian axis with a precocious maturation through damage of GnRH pulsatility, gonadotropin signaling, and sex steroid hormone production. Further, BPA exposure during the early life stage may have a transgenerational effect predisposing the subsequent generations to the risk of developing BPA-related disease. Experimental studies suggested that prenatal, perinatal, and postnatal exposure to BPA can impair several steps of ovarian development and impair ovarian function, particularly folliculogenesis. Uterus morphology and function are also affected by endocrine disruptors. Studies carried out in animal models have reported the occurrence of endometriosis-like lesions after BPA exposure. Moreover, BPA exposure has been described to cause PCOS-like abnormalities.