TY - JOUR
T1 - Putative adverse outcome pathways for female reproductive disorders to improve testing and regulation of chemicals
AU - Johansson, Hanna K.L.
AU - Damdimopoulou, Pauliina
AU - van Duursen, Majorie B.M.
AU - Boberg, Julie
AU - Franssen, Delphine
AU - de Cock, Marijke
AU - Jääger, Kersti
AU - Wagner, Magdalena
AU - Velthut-Meikas, Agne
AU - Xie, Yuling
AU - Connolly, Lisa
AU - Lelandais, Pauline
AU - Mazaud Guittot, Séverine
AU - Salumets, Andres
AU - Draskau, Monica Kam
AU - Filis, Panagiotis
AU - Fowler , Paul A.
AU - Christiansen, Sofe
AU - Parent, Anne-Simone
AU - Svingen, Terje
N1 - Funding
This work was funded by the EU Horizon 2020 project FREIA (Grant Number 825100).
PY - 2020/10
Y1 - 2020/10
N2 - Modern living challenges female reproductive health. We are witnessing a rise in reproductive disorders and drop in birth rates across the world. The reasons for these manifestations are multifaceted and most likely include continuous exposure to an ever-increasing number of chemicals. The cause–effect relationships between chemical exposure and female reproductive disorders, however, have proven problematic to determine. This has made it difcult to assess the risks chemical exposures pose to a woman’s reproductive development and function. To address this challenge, this review uses the adverse outcome pathway (AOP) concept to summarize current knowledge about how chemical exposure can afect female reproductive health. We have a special focus on efects on the ovaries, since they are essential for lifelong reproductive health in women, being the source of both oocytes and several reproductive hormones, including sex steroids. The AOP framework is widely accepted as a new tool for toxicological safety assessment that enables better use of mechanistic knowledge for regulatory purposes. AOPs equip assessors and regulators with a pragmatic network of linear cause–efect relationships, enabling the use of a wider range of test method data in chemical risk assessment and regulation. Based on current knowledge, we propose ten putative AOPs relevant for female reproductive disorders that can be further elaborated and potentially be included in the AOPwiki. This efort is an important step towards better safeguarding the reproductive health of all girls and women.
AB - Modern living challenges female reproductive health. We are witnessing a rise in reproductive disorders and drop in birth rates across the world. The reasons for these manifestations are multifaceted and most likely include continuous exposure to an ever-increasing number of chemicals. The cause–effect relationships between chemical exposure and female reproductive disorders, however, have proven problematic to determine. This has made it difcult to assess the risks chemical exposures pose to a woman’s reproductive development and function. To address this challenge, this review uses the adverse outcome pathway (AOP) concept to summarize current knowledge about how chemical exposure can afect female reproductive health. We have a special focus on efects on the ovaries, since they are essential for lifelong reproductive health in women, being the source of both oocytes and several reproductive hormones, including sex steroids. The AOP framework is widely accepted as a new tool for toxicological safety assessment that enables better use of mechanistic knowledge for regulatory purposes. AOPs equip assessors and regulators with a pragmatic network of linear cause–efect relationships, enabling the use of a wider range of test method data in chemical risk assessment and regulation. Based on current knowledge, we propose ten putative AOPs relevant for female reproductive disorders that can be further elaborated and potentially be included in the AOPwiki. This efort is an important step towards better safeguarding the reproductive health of all girls and women.
KW - ovary
KW - reproduction
KW - Adverse outcome pathway
KW - AOP
KW - Ovarian dysgenesis syndrome
KW - ODS
KW - Endocrinedisrupting chemicals
KW - EDC
KW - Ovary
KW - Reproduction
KW - Endocrine-disrupting chemicals
KW - POLYCYSTIC-OVARY-SYNDROME
KW - IN-UTERO EXPOSURE
KW - ANTI-MULLERIAN HORMONE
KW - ENDOCRINE DISRUPTING CHEMICALS
KW - PRIMORDIAL FOLLICLE
KW - BISPHENOL-A EXPOSURE
KW - LESS CONFUSING TERMINOLOGY
KW - GENE-EXPRESSION
KW - GERM-CELL
KW - ORGANOCHLORINE PESTICIDES
UR - http://www.scopus.com/inward/record.url?scp=85087607880&partnerID=8YFLogxK
U2 - 10.1007/s00204-020-02834-y
DO - 10.1007/s00204-020-02834-y
M3 - Review article
C2 - 32638039
SN - 0340-5761
VL - 94
SP - 3359
EP - 3379
JO - Archives of Toxicology
JF - Archives of Toxicology
IS - 10
ER -