Andrographolide disrupts meiotic maturation by blocking cytoskeletal reorganisation and decreases the fertilisation potential of mouse oocytes

Abstract

Andrographolide (AG) is a diterpenoid lactone isolated from the stem and leaves of Andrographis paniculata Nees that is used for the effective treatment of infectious diseases in Asian countries. Previous studies have reported adverse effects of AG on female fertility in rodents; however, the underlying mechanisms are unknown. The aim of the present study was to investigate the effects of AG on the IVM of mouse oocytes and their fertilisation potential. Immature oocytes incubated for 6, 14 or 24h in medium containing 5, 10 or 20μM AG showed time- and dose-dependent decreases in maturation rates compared with the control group. Immunostaining revealed that AG exposure disrupted spindle organisation and migration, as well as actin cap formation and cytokinesis. Furthermore, most oocytes exposed to 20μM AG underwent apoptosis, and the few oocytes exposed to 5 or 10μM AG that reached MII exhibited lower fertilisation rates after intracytoplasmic sperm injection. The findings of the present study suggest that AG may disrupt mouse oocyte meiotic maturation by blocking cytoskeletal reorganisation, and may thus have an adverse effect on female fertility.

Andrographolide: A review of its pharmacology, pharmacokinetics, toxicity and clinical trials and pharmaceutical researches

“…Unexpectedly, it is applied to induce reproductive function defect model in basic clinical research owing to this side effect (Chung, Chan, & Lee, 2021). A study on the adverse effects of andrographolide on the reproductive capacity of female rodents showed that, it destroyed the spindle tissue and migration, as well as the formation of actin cap and cytokinesis, simultaneously, it caused the apoptosis of most oocytes at the concentration of 20 μM, and reduced the fertilization rate of a few oocytes after intracytoplasmic sperm injection, which this adverse reproductive effect may be achieved by blocking the reorganization of cytoskeleton and destroying the meiotic maturation of mouse oocytes (Liang et al, 2017). Based on the human embryonic stem cells (hESCs) and CBA/b6 F1 hybrid mice model, the researchers confirmed that andrographis had notable reproductive toxicity, which is manifested in the increase of ROS level, mitochondrial membrane potential damage, caspase‐3 induction and up‐regulation of the expression of nuclear factor 2 related factor 2 (Nrf2) protein and its target gene (Huang et al, 2019).…”

Novel wine in an old bottle: Preventive and therapeutic potentials of andrographolide in atherosclerotic cardiovascular diseases

“…If some patients have reproductive requirement, they can stop taking AG and prepare to give births after the reproductive indexes were reversed. Furthermore, AG had been demonstrated to destroy the maturation and fertilization potential of female oocytes [ 190 ]. However, further in vivo studies in animals and clinical trials in humans are needed to determine whether AG caused reproductive toxicity in females.…”

“…Additionally, AG could disrupt the formation of actin cap, promote oocyte apoptosis and decrease the fertility of mature oocytes in vitro. Overall, AG adversely affected the fertility of female mice by interfering with the meiosis of oocytes [ 190 ]. Huang et al.…”

Anti-Cancer Agent: The Labdane Diterpenoid-Andrographolide

“…Moreover, andrographolide increased C/EBP homologous protein (CHOP) and caspase-4 by inducing damage at the endoplasmic reticulum level [ 136 ]. Successively, Liang et al [ 137 ] have demonstrated that andrographolide reduced the reproductive capacity of female rodents and caused the apoptosis of most oocytes. In addition, mild adverse events, including rash and taste disturbance, emerged from a clinical study in which andrographolide was orally administered twice daily at a dose of 140 mg [ 138 ].…”