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Cadmium increases human fetal germ cell apoptosis
Gaëlle Angenard1, Vincent Muczynski, Hervé Coffigny
1Laboratory of Differentiation and Radiobiology of the Gonads, CEADSV/iRCM/SCSR, Fontenay aux Roses, France. gabriel.livera@cea.fr
Background:
Cadmium (Cd) is a common environmental pollutant and a major constituent of tobacco smoke. Adverse effects of this heavy metal on reproductive function have been identified in adults; however, no studies have examined its effects on human reproductive organs during development.
Objectives:
Using our previously developed organ culture system, we investigated the effects of cadmium chloride on human gonads at the beginning of fetal life, a critical stage in the development of reproductive function.
Methods:
Human fetal gonads were recovered during the first trimester (711 weeks postconception) and cultured with or without Cd. We used different concentrations of Cd and compared results with those obtained with mouse fetal gonads at similar stages.
Results:
Cd, at concentrations as low as 1 microM, significantly decreased the germ cell density in human fetal ovaries. This correlated with an increase in germ cell apoptosis, but there was no effect on proliferation. Similarly, in the human fetal testis, Cd (1 microM) reduced germ cell number without affecting testosterone secretion. In mouse fetal gonads, Cd increased only female germ cell apoptosis.
Conclusions:
This is the first experimental demonstration that Cd, at low concentrations, alters the survival of male and female germ cells in humans. Considering data demonstrating extensive human exposure, we believe that current environmental levels of Cd could be deleterious to early gametogenesis.
Insights
Cadmium (Cd) exposure harms developing human reproductive cells, decreasing germ cell numbers in both male and female fetuses. This early-life exposure to environmental cadmium may negatively impact future fertility.
Area of Science:
- Reproductive Biology
- Developmental Toxicology
- Environmental Health
Background:
- Cadmium (Cd) is an environmental pollutant and tobacco smoke component.
- Adult reproductive function is known to be affected by cadmium.
- Effects of cadmium on developing human reproductive organs are unknown.
Purpose of the Study:
- Investigate the impact of cadmium chloride on human fetal gonads.
- Examine effects during early fetal development, a critical reproductive period.
Main Methods:
- Human fetal gonads (7-11 weeks postconception) were cultured.
- Organ cultures were exposed to varying concentrations of cadmium chloride.
- Results were compared with mouse fetal gonad studies.
Main Results:
- Low cadmium concentrations (1 microM) reduced germ cell density in human fetal ovaries.
- Cadmium increased germ cell apoptosis in human fetal ovaries, without affecting proliferation.
- Cadmium (1 microM) decreased germ cell number in human fetal testes, without impacting testosterone secretion.
- Cadmium exposure increased germ cell apoptosis in mouse fetal ovaries, but not testes.
Conclusions:
- First evidence that low cadmium concentrations affect human male and female germ cell survival during development.
- Current environmental cadmium levels may be harmful to early gametogenesis.
- Highlights potential risks of environmental cadmium exposure to human reproductive health.
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