AOP Report: An Upstream Network for Reduced Androgen Signaling Leading to Altered Gene Expression of Androgen Receptor-Responsive Genes in Target Tissues.

Adverse outcome pathways (AOPs) can aid with chemical risk assessment by providing plausible links between chemical activity at the molecular level and effect outcomes in intact organisms. Because AOPs can be used to infer causality between upstream and downstream events in toxicological pathways, the AOP framework can also facilitate increased uptake of alternative methods and new approach methodologies to help inform hazard identification. However, a prevailing challenge is the limited number of fully developed and endorsed AOPs, primarily due to the substantial amount of work required by AOP developers and reviewers.

Exposure to the phthalate metabolite MEHP impacts survival and growth of human ovarian follicles in vitro.

Phthalates are found in everyday items like plastics and personal care products. There is an increasing concern that continuous exposure can adversely affect female fertility. However, experimental data are lacking to establish causal links between exposure and disease in humans.

Identification of biomarkers and outcomes of endocrine disruption in human ovarian cortex using In Vitro Models.

Endocrine disrupting chemicals (EDCs) are raising concerns about adverse effects on fertility in women. However, there is a lack of information regarding mechanisms and effects in humans. Our study aims to identify mechanisms of endocrine disruption using two EDCs, diethylstilbestrol (DES) and ketoconazole (KTZ).

AOP key event relationship report: Linking decreased androgen receptor activation with decreased granulosa cell proliferation of gonadotropin-independent follicles.

We recently proposed to formally recognize Key Event Relationships (KERs) as building blocks of Adverse Outcome Pathways (AOPs) that can be independently developed and peer-reviewed. Here, we follow this approach and provide an independent KER from AOP345, which describes androgen receptor (AR) antagonism leading to decreased female fertility. This KER connects AR antagonism to reduced granulosa cell proliferation of gonadotropin-independent follicles (KER2273).

A Pragmatic Approach to Adverse Outcome Pathway Development and Evaluation.

The adverse outcome pathway (AOP) framework provides a practical means for organizing scientific knowledge that can be used to infer cause-effect relationships between stressor events and toxicity outcomes in intact organisms. It has reached wide acceptance as a tool to aid chemical safety assessment and regulatory toxicology by supporting a systematic way of predicting adverse health outcomes based on accumulated mechanistic knowledge. A major challenge for broader application of the AOP concept in regulatory toxicology, however, has been developing robust AOPs to a level where they are peer reviewed and accepted.

Phthalates, ovarian function and fertility in adulthood.

Phthalates are a family of high-production volume industrial chemicals used in the manufacture of plastics. Some phthalates are regulated as endocrine disrupting chemicals (EDCs) and reproductive toxicants based on adverse effects in the male. Potential effects in females are less understood although exposure levels can be higher in women compared to men.