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Cadmium downregulates ZnT‐4 and induces mammary gland involution in lactating mice
Author(s) -
Tallkvist Jonas,
Huang Liping,
Öhrvik Helena
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.lb247
Subject(s) - involution (esoterism) , cadmium , metallothionein , offspring , medicine , endocrinology , mammary gland , biology , downregulation and upregulation , histopathology , andrology , chemistry , gene , pathology , biochemistry , genetics , pregnancy , cancer , breast cancer , consciousness , organic chemistry , neuroscience
Numerous studies in various species have shown that cadmium (Cd) is retained in the lactating mammary gland (LMG) and is only poorly transferred to milk suggesting that the LMG may act as a barrier to protect the suckling offspring from exposure to Cd. The mechanism for the Cd retention is unknown but may involve interaction with metallothionein (MT) or members of the family of zinc transporters (ZnTs). The aim of the present study was to examine the morphology of the LMG and protein expressions of MT, ZnT‐2, ZnT‐4 or ZnT‐7 in Cd treated mice. A total of 12 primiparous NMRI dams with normalized litter sizes (n=8) were given 17.8 umol Cd/kg/day or vehicle on postnatal days (PND) 8, 9 and 10. Left inguinal mammary glands (4 and 5) were dissected on PND 11 for morphological examination, Zn‐analyses and immunoblotting. Livers were taken from the dams for MT westerns. The histopathology demonstrated increased fat content in the LMG of the Cd treated dams and a less active feature of the alveolar epithelium as compared to the controls, indicating a Cd induced involution. Total Zn‐levels in the LMG were unaffected by Cd. ZnT‐4 protein was significantly downregulated as a result of the Cd treatment whereas MT, ZnT‐2 and ZnT‐7expressions were unaffected. Liver MT was upregulated in the Cd treated dams. Our results indicate that Cd induces involution of the LMG and that ZnT‐4 is involved in this process.