Cadmium increases human fetal germ cell apoptosis.
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.


OBJECTIVE
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.
Angenard
Gaëlle
G
Laboratory of Differentiation and Radiobiology of the Gonads, CEADSV/iRCM/SCSR, Fontenay aux Roses, France. gabriel.livera@cea.fr
Muczynski
Vincent
V
Coffigny
Hervé
H
Pairault
Catherine
C
Duquenne
Clotilde
C
Frydman
René
R
Habert
René
R
Rouiller-Fabre
Virginie
V
Livera
Gabriel
G
D000328:Adult; D000393:Air Pollutants / Q000633:toxicity*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002104:Cadmium / Q000633:toxicity*; D005260:Female; D005333:Fetus / Q000033:anatomy & histology / Q000166:cytology*; D005854:Germ Cells / Q000166:cytology / Q000187:drug effects*; D006066:Gonads / Q000166:cytology / Q000187:drug effects / Q000196:embryology; D006801:Humans; D008297:Male; D018811:Maternal Exposure / Q000009:adverse effects*; D051379:Mice; D009924:Organ Culture Techniques; D011247:Pregnancy; D011261:Pregnancy Trimester, First
D000393:Air Pollutants; D002104:Cadmium