Transgenerational Effects of Periconception Heavy Metal Administration on Adipose Weight and Glucose Homeostasis in Mice at Maturity.
Toxicol Sci
; 168(2): 610-619, 2019 04 01.
Article
en En
| MEDLINE
| ID: mdl-30629257
We previously demonstrated that periconception maternal administration (2 mg/kg body weight each) of cadmium chloride (CdCl2) plus methylmercury (II) chloride (CH3HgCl) impaired glucose homeostasis and increased body weights and abdominal adipose tissue weight of male offspring in the F1 generation. However, transgenerational effects of this exposure have not been studied. Therefore, the effects of periconception Cd+Hg administration on indices of chronic diseases at adulthood in F2-F4 generations were examined. Male and female progeny of Cd+Hg periconceptionally treated females, and offspring of vehicle control females were bred with naïve CD1 mice to obtain F2 offspring, with additional crosses as above to the F4 generation (F1-F4 animals were not administered Cd+Hg). Birth weights and litter size were similar in all generations. Indices of impaired glucose homeostasis were observed in matrilineally descended F2 male offspring, including reduced glucose tolerance, along with increased basal phosphorylation of insulin receptor substrate 1 (IRS1) at serine 307 suggesting altered insulin signaling. Reduced glucose tolerance was also seen in F4 males. Increased body weight and/or abdominal adiposity were observed through the F4 generation in males descended matrilineally from the treated female progenitors. Patrilineally derived F2 females displayed reduced glucose tolerance. Females (F2) patrilineally and matrilineally derived displayed significant kidney enlargement. Periconception administration of cadmium and mercury caused persistent transgenerational effects in offspring through the F4 generation in the absence of continued toxicant exposure, with persistent transgenerational effects inherited specifically through the matrilineal germline.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Tamaño de los Órganos
/
Efectos Tardíos de la Exposición Prenatal
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Tejido Adiposo
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Metales Pesados
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Glucosa
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Homeostasis
Límite:
Animals
/
Pregnancy
Idioma:
En
Revista:
Toxicol Sci
Asunto de la revista:
TOXICOLOGIA
Año:
2019
Tipo del documento:
Article
Pais de publicación:
Estados Unidos