Objective To investigate the effects of lead exposure on rat placental apoptosis during different periods of pregnancy. Methods All Wistar rats were randomly divided into four groups with 27 for each group with the sex ratio of 2 : 1 (female : male).The groups with lead exposure consumed water with 0. 025％ lead acetate during the entire, early or late period of pregnancy. Controls were given distilled water without lead.Blood lead levels were determined by atomic absorption spectrophotometry at the end of pregnancy. Placental apoptosis were assessed by both Hoechst staining and terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling (TUNEL) assay. Data were assessed by one-way analysis of variance, and differences between groups were compared by q-test. ResultsBlood lead levels at the end of pregnancy of the groups with lead exposure (entire, early or late pregnancy) and the control group were (1. 74±0. 19) μmol/L,(1.27±0.26) μmol/L, (0.60±0. 11) μmol/L and (0.04±0.01) μmol/L respectively(F= 12. 10,P＜0.01).In the groups with lead exposure, Hoechst staining showed hyperchromatic nuclei in placental trophoblast apoptotic cells and compact fluorescent particles in some nucleus； TUNEL assay showed brown-staining apoptotic cells nuclei with some nuclei particles staining brown. Two assays showed the same results: the apoptotic index of the groups with lead exposure were higher than that of the control group; the apoptosis index of the group with lead exposure during entire pregnancy was higher than that of the group with lead exposure during early and late pregnancy (P ＜ 0. 05).ConclusionsLead exposure during pregnancy could elevate the blood levels of lead and the degree of placental apoptosis.

BACKGROUNDLead exposure during pregnancy contributes to fetal abortion and/or teratogenesis. Endoplasmic reticulum (ER) apoptosis can be induced by various pathological conditions when ER function is disturbed. However, it is unclear whether ER stress and apoptosis play a role in the etiology of lead-exposed disease status. We aimed to investigate whether lead induced placental apoptosis and subsequent toxicity is initiated by ER apoptosis via caspase-12.

METHODSSixty-three female Wistar rats were exposed to lead in drinking water during various gestational periods. Blood lead level was determined by atomic absorption spectrophotometry. Placental cytoplasmic organelles were examined by electronic microscopy. Placental caspase-12 mRNA expression was evaluated by qRT-PCR. TUNEL assay was used to determine the placental apoptosis.

RESULTSLead exposure significant induced ER apoptosis compared to that of the controls (P < 0.05), accompanied with increased caspase-12 mRNA expression. Significant differences of caspase-12 mRNA expression levels were observed among the four groups (F = 13.78, P < 0.05). Apoptotic index (AI) was significantly increased in experimental groups compared to that of the controls (F = 96.15, P < 0.05). In lead-exposed groups, trophoblast cells underwent degeneration and fibrin deposition; Mitochondria were swollen and decreased in number; ER swelling, expansion, and vacuolization were observed.

CONCLUSIONLead exposure contributes to placental apoptosis, as well as increased caspase-12 mRNA expression, which in turn promoted ER stress.

Animals ; Apoptosis ; drug effects ; Endoplasmic Reticulum Stress ; drug effects ; Female ; Lead ; toxicity ; Placenta ; cytology ; ultrastructure ; Pregnancy ; Rats ; Rats, Wistar