Abstract
Hexestrol (HES) is a synthetic non-steroidal estrogen that was widely used illegally to boost the growth rate in livestock production and aquaculture. HES can also be transferred to humans from treated animals and the environment. HES has been shown to have an adverse effect on ovarian function and oogenesis, but the potential mechanism has not been clearly defined. To understand the potential mechanisms regarding how HES affect female ovarian function, we assessed oocyte quality by examining the critical events during oocyte maturation. We found that HES has an adverse effect on oocyte quality, indicated by the decreased capacity of oocyte maturation and early embryo development competency. Specifically, HES-exposed oocytes exhibited aberrant microtubule nucleation and spindle assembly, resulting in meiotic arrest. In addition, HES exposure disrupted mitochondrial distribution and the balance of mitochondrial fission and fusion, leading to aberrant mitochondrial membrane potential and accumulation of reactive oxygen species. Lastly, we found that HES exposure can increase cytosolic Ca2+ levels and induce DNA damage and early apoptosis. In summary, these results demonstrate that mitochondrial dysfunction and perturbation of normal mitochondrial fission and fusion dynamics could be major causes of reduced oocyte quality after HES exposure.
Highlights
Environmental pollution is becoming a major threat to human health
To identify the effect of HES on female reproduction, the body weight and ovary morphology of adult female mice were examined after 30 days of exposure to HES
We observed that the structure of mature follicles was impaired, demonstrating that HES exposure had an adverse effect on ovary function and folliculogenesis
Summary
One emerging group of contaminants, endocrine-disrupting chemicals (EDCs), is exogenous substances or mixtures that cause dysfunction of the endocrine system, inducing multiple adverse health effects in humans through interaction with hormone receptors (Schug et al, 2016). EDCs usually affect hormone–receptor interactions, corpus luteum formation, Hexestrol on Oocyte Maturation sex steroid synthesis, and folliculogenesis, resulting in irreversible reproductive issues such as estrogen deficiency, dysfunctional ovulation, premature ovarian insufficiency, endometriosis, polycystic ovarian syndrome, or infertility (Craig et al, 2011; Hamid et al, 2021). Humans are exposed to environmental HES directly, but it can pass through the food chain to the human body, and it interferes with normal physiological processes, resulting in severe health problems such as cancer, endometriosis, fetal malformation, and metabolic disorders (Saeed et al, 2005; Cavalieri and Rogan, 2006; Chen et al, 2015; Feng et al, 2016)
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