Malott, K. F., & Luderer, U. (2021). Toxicant effects on mammalian oocyte mitochondria†. Biology of reproduction. https://doi.org/10.1093/biolre/ioab002
Malott KF, Luderer U. Toxicant effects on mammalian oocyte mitochondria†. Biology of reproduction. 2021. doi:10.1093/biolre/ioab002
Malott, K. F., and U. Luderer. "Toxicant effects on mammalian oocyte mitochondria†." Biology of reproduction, 2021.
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RRM Academy Synopsis
Toxic exposures can damage oocyte mitochondria in animal studies
A 2021 review of animal studies reports that chemotherapy drugs, metals and pesticides can damage mitochondria in animal egg cells. Mitochondria power the oocyte. The authors note that mitochondrial dysfunction has been linked to lower female fertility.
Key Findings
Primordial germ cells start with a founder population of only 10 mitochondria. A healthy mature oocyte holds roughly 100 000 in the mouse and 300 000–400 000 in the human.
Adult mice exposed to nitrogen mustard for 48 hours had oocytes with more mitochondrial superoxide and smaller mitochondrial volume. Acrolein, a cyclophosphamide derivative, lowered mitochondrial membrane potential in oocytes at high concentrations.
Females given cadmium for 35 days had oocytes with lower ATP content than controls. Arsenite-treated mice produced oocytes with spindle abnormalities in 25% and 62.5% at two doses, against none in controls.
Ovarian mitochondria isolated from methoxychlor-treated adult mice showed decreased ADP-stimulated respiration and increased hydrogen peroxide production.
Neonatal mice given benzo(a)pyrene for seven consecutive days had oocytes at 6 weeks of age with a dose-dependent increase in mitochondrial superoxide production and lipid peroxidation.
Interpretation
The authors review experiments in animals and cultured cells. The studies measured mitochondrial and oxidative changes in oocytes, embryos and ovaries after toxic exposures. The authors note that the glyphosate level used in culture was far above human exposure levels. They contend that much more research is needed, including on effects across generations.
RRM Context
Restorative reproductive medicine looks for the cause of infertility. Damage to egg mitochondria is one way that toxic exposures could be a cause. The authors add that offspring inherit mitochondria from the egg, so a mother's exposures could reach the next generation.
Our editorial summary of this paper, not the article's abstract.
Abstract
Oocyte mitochondria are unique organelles that establish a founder population in primordial germ cells (PGCs). As the oocyte matures in the postnatal mammalian ovary during folliculogenesis it increases exponentially in volume, and the oocyte mitochondria population proliferates to about 100 000 mitochondria per healthy, mature murine oocyte. The health of the mature oocyte and subsequent embryo is highly dependent on the oocyte mitochondria. Mitochondria are especially sensitive to toxic insults, as they are a major source of reactive oxygen species (ROS), they contain their own DNA (mtDNA) that is unprotected by histone proteins, they contain the electron transport chain that uses electron donors, including oxygen, to generate ATP, and they are important sensors for overall cellular stress. Here we review the effects that toxic insults including chemotherapeutics, toxic metals, plasticizers, pesticides, polycyclic aromatic hydrocarbons (PAHs), and ionizing radiation can have on oocyte mitochondria. This is very clearly a burgeoning field, as our understanding of oocyte mitochondria and metabolism is still relatively new, and we contend much more research is needed to understand the detrimental impacts of exposure to toxicants on oocyte mitochondria. Developing this field further can benefit our understanding of assisted reproductive technologies and the developmental origins of health and disease (DOHaD).
