Gestational Cd Exposure in the CD-1 Mouse Induces Sex-Specific Hepatic Insulin Insensitivity, Obesity, and Metabolic Syndrome in Adult Female Offspring

• DOI: 10.1093/toxsci/kfaa154
• Publication Date: 2020-10-14T19:22:51Z
• Authors: Thomas W Jackson; Garret L Ryherd; Chris M Scheibly; Aubrey L Sasser; T C Guillette; Scott M Belcher
• Keywords: Male; Metabolic Syndrome; 2. Zero hunger; 0303 health sciences; 3. Good health; Mice; 03 medical and health sciences; Sex Factors; Cadmium Chloride; Diabetes Mellitus, Type 2; Liver; Pregnancy; Prenatal Exposure Delayed Effects; Animals; Female; Obesity; Insulin Resistance; Cadmium

Abstract There is compelling evidence that developmental exposure to toxic metals increases risk for obesity and obesity-related morbidity including cardiovascular disease type 2 diabetes. To explore the hypothesis Cd of later in life, male, female CD-1 mice were maternally exposed 500 ppb CdCl2 drinking water during a human gestational equivalent period (gestational day 0-postnatal 10 [GD0-PND10]). Hallmark indicators metabolic disruption, hepatic steatosis, syndrome evaluated prior birth through adulthood. Maternal blood levels similar those observed pregnancy cohorts, was undetected adult offspring. no impacts on dams or pregnancy-related outcomes. Results glucose insulin tolerance testing revealed impaired offspring homeostasis PND42. Exposure-related circulating triglycerides steatosis apparent only females. By PND120, Cd-exposed females 30% heavier with 700% more perigonadal fat than unexposed control dyslipidemia, increased weight gain, nor adiposity male Hepatic transcriptome analysis PND1, PND21, PND42 female-specific oxidative stress mitochondrial dysfunction significant early disruption retinoic acid signaling altered receptor consistent sensitivity The syndrome-like phenotypes resulting from pre- perinatal development gestation indicate acts developmentally as sex-specific delayed obesogen.