ESPE Yearbook of Paediatric Endocrinology

To read the full abstract: Environmental health perspectives vol. 127,10 (2019): 107011. doi: https://ehp.niehs.nih.gov/doi/full/10.1289/EHP5570?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed

This study identifies the effects of exposure to environmentally relevant doses of bisphenol A (BPA) on the development of hypothalamic kiss1/NKB neurons in female mice.

Bisphenol A (BPA) is a compound with estrogenic activity, which is widely used in the production of polycarbonate plastics and epoxy resins (1). It is the most studied endocrine-disrupting chemical and is potentially involved in a wide array of health problems including reproductive disorders (2–3). Puberty is an important marker of reproductive health at the population level, and may be correlated with downstream outcomes, such as irregular estrous cycles and reduced fertility. However, studies focusing on timing of pubertal onset report divergent results, ranging from no effect of BPA, to a delay, or early onset of puberty.

Using a mouse model, the authors showed that perinatal exposure to BPA significantly advances age at vaginal opening, a measure of puberty onset in female mice, consistent with some previous studies (4–5). The novelty of this study is the use of very low-doses of BPA given orally to the mothers which reinforces the clinical relevance of the data. Mice exposed perinatally to BPA exhibited a persistent, but divergent, impairment of Kiss1 neuronal maturation, with more kisspeptin cells in the rostral (RP3V) hypothalamus but consistently fewer kisspeptin neurons in the arcuate nucleus (ARC). Mice exposed to BPA had persistently lower Kiss1 expression during (pre)pubertal maturation, which was associated with lower Tac2 (encoding NKB) levels.

This comprehensive analysis illustrates the exquisite sensitivity of the Kiss1/NKB system to endocrine disruptors. Detecting brain region-specific BPA effects is a novel contribution and provides a potential explanation for abnormal programming of puberty. It draws attention to the necessity of precautionary measures concerning exposure to BPA, even at low doses that are currently considered as safe.

References:

1. Vandenberg LN, Hauser R, Marcus M, Olea N, Welshons WV. Human exposure to bisphenol A (BPA). Reprod Toxicol. 2007;24 (2):139–177.

2. Dickerson SM, Cunningham SL, Gore AC. Reproductive Neuroendocrine Targets of Developmental Exposure to Endocrine Disruptors. Endocrine Disruptors and Puberty. Contemporary Endocrinology. Humana Press. 2012;49–117.

3. Parent AS, Franssen D, Fudvoye J, Pinson A, Bourguignon JP. Current Changes in Pubertal Timing: Revised Vision in Relation with Environmental Factors Including Endocrine Disruptors. Endocr Dev. 2016;29:174–184.

4. Losa-Ward SM, Todd KL, McCaffrey KA, Tsutsui K, Patisaul HB. Disrupted organization of RFamide pathways in the hypothalamus is associated with advanced puberty in female rats neonatally exposed to bisphenol A. Biol Reprod. 2012;87 (2):28. Published 2012 Aug 2.

5. Fernández M, Bianchi M, Lux-Lantos V, Libertun C. Neonatal exposure to bisphenol a alters reproductive parameters and gonadotropin releasing hormone signaling in female rats. Environ Health Perspect. 2009;117 (5):757–762.