4.6 Review

Cellular and molecular features of EDC exposure: consequences for the GnRH network

Journal

NATURE REVIEWS ENDOCRINOLOGY
Volume 17, Issue 2, Pages 83-96

Publisher

NATURE RESEARCH
DOI: 10.1038/s41574-020-00436-3

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Funding

  1. NIH HHS [P51 OD011092] Funding Source: Medline

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This article discusses the potential long-term reproductive consequences of perinatal exposure to endocrine-disrupting chemicals, focusing on the cellular and molecular impacts under neuroendocrine control. Exposure to EDCs during critical development periods may affect brain development, pubertal timing, and the female ovulatory cycle, ultimately leading to impaired fertility.
Exposure to environmental pollutants such as endocrine-disrupting chemicals (EDCs) during critical periods of development can have long-term reproductive consequences. This Review discusses the cellular and molecular consequences of perinatal exposure EDCs with a focus on the neuroendocrine control of reproduction. The onset of puberty and the female ovulatory cycle are important developmental milestones of the reproductive system. These processes are controlled by a tightly organized network of neurotransmitters and neuropeptides, as well as genetic, epigenetic and hormonal factors, which ultimately drive the pulsatile secretion of gonadotropin-releasing hormone. They also strongly depend on organizational processes that take place during fetal and early postnatal life. Therefore, exposure to environmental pollutants such as endocrine-disrupting chemicals (EDCs) during critical periods of development can result in altered brain development, delayed or advanced puberty and long-term reproductive consequences, such as impaired fertility. The gonads and peripheral organs are targets of EDCs, and research from the past few years suggests that the organization of the neuroendocrine control of reproduction is also sensitive to environmental cues and disruption. Among other mechanisms, EDCs interfere with the action of steroidal and non-steroidal receptors, and alter enzymatic, metabolic and epigenetic pathways during development. In this Review, we discuss the cellular and molecular consequences of perinatal exposure (mostly in rodents) to representative EDCs with a focus on the neuroendocrine control of reproduction, pubertal timing and the female ovulatory cycle.

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