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

• Published in: Nature reviews. Endocrinology Vol. 17; no. 2; pp. 83 - 96
• Main Authors: Lopez-Rodriguez, David, Franssen, Delphine, Bakker, Julie, Lomniczi, Alejandro, Parent, Anne-Simone
• Format: Journal Article Web Resource
• Language: English
• Published: London Nature Publishing Group UK 01.02.2021; Nature Publishing Group
• Subjects: 692/163/2743/2742; 692/699/2732/2730; 692/699/2743/1526; 692/700/478; Animals; Cell Movement; DNA Methylation - drug effects; Endocrine disruptors; Endocrine Disruptors - pharmacology; Endocrinologie, métabolisme & nutrition; Endocrinology; Endocrinology, metabolism & nutrition; Environmental aspects; Environmental Exposure; Epigenesis, Genetic - drug effects; Epigenetics; Estradiol - metabolism; Feedback, Physiological - drug effects; Female; Fertility; Fetuses; GABA Agents - metabolism; Germ Cells - metabolism; Glutamic Acid - metabolism; Gonadotropin releasing hormone; Gonadotropin-Releasing Hormone - drug effects; Gonadotropin-Releasing Hormone - metabolism; Gonadotropins; Gonads; Health aspects; Histone Code - drug effects; Human health sciences; Human reproduction; Humans; Hypothalamus - cytology; Hypothalamus - drug effects; Hypothalamus - growth & development; Hypothalamus - metabolism; Infertility; Kisspeptins - metabolism; Male; Medicine; Medicine & Public Health; Metabolic diseases; Neurons - drug effects; Neurons - metabolism; Neuropeptides; Neurotransmitters; Ovulation - drug effects; Ovulation - metabolism; Pediatrics; Perinatal exposure; Physiological aspects; Pituitary (anterior); Pollutants; Pregnancy; Prenatal Exposure Delayed Effects; Puberty; Pédiatrie; Reproduction; Reproductive system; Review Article; Risk factors; Sciences de la santé humaine; Belgium
• ISSN: 1759-5029; 1759-5037; 1759-5037
• DOI: 10.1038/s41574-020-00436-3

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. 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. Key points Endocrine-disrupting chemicals (EDCs) interfere with the cellular organization of the hypothalamus, leading to persistent alterations of the reproductive axis. The epigenetic, molecular and cellular organization of the gonadotropin-releasing hormone network is most vulnerable to EDCs during early development. Effects of EDCs are not limited to classic agonist or antagonist action on sex steroid receptors but also induce long-lasting gene expression and epigenetic changes in the developing brain. The study of low-dose complex mixtures is required to mimic real-world situations and better relate animal model studies to epidemiological data.