Table 1:

Developmental environmental factors linked to CVD

Environmental factor	Window of exposure	Model	Phenotype	Sex specificity	Reference
Famine	First trimester in utero	Human	Obesity, dyslipidemia (high LDL: HDL cholesterol ratio), cardiovascular disease (angina pectoris, Q waves on the ECG, or history of coronary revascularization)	Effect on obesity was observed in women at 50 years of age	[10,12]
Famine	Third trimester in utero	Human	Reduced risk of obesity	Study was conducted on men at 19 years of age	[11]
Obesogenic diet (high fat and high sugar) and obesity during pregnancy	Gestation and lactation	Mouse	Reduction in cardiac function at 32 weeks of age—hypertrophy and diastolic dysfunction	Only effects on male offspring were reported	[14]
Hyperglycemia	Gestation	Mouse	In embryos, impaired formation of left-right axis in heart and left-right asymmetry in developing organs	Not reported	[15]
High-fat and high-sucrose diet	Gestation and lactation	Mouse	Higher left ventricular weight in males and females, smaller left ventricular relative wall thickness in females, higher left ventricular relative wall thickness in males, cardiac mitochondrial abnormalities in both sexes	Yes	[16]
Protein restriction	Gestation and lactation	Rat	Decreased mitochondrial oxidative phosphorylation, decreased antioxidant capacity, and increased reactive oxygen species	Only male offspring were evaluated	[17]
Adverse childhood experiences (abuse, neglect, violence, and household dysfunction)	First 18 years of life	Human	Impaired endothelial function and reduced circulating levels of SIRT1	Only females were evaluated	[18]
Adverse childhood experiences (abuse, neglect, and household dysfunction)	First 18 years of life	Human	Increased risk of ischemic heart disease (mediated by psychosocial factors)	Sex differences not reported	[19]
Adverse childhood experiences (verbal and physical abuse, substance abuse, and poorly managed household)	First 18 years of life	Human	Increased multisystem health risk (high blood pressure, low heart rate variability, dyslipidemia, waist circumference, and other factors)	Sex differences not reported	[20]
PM2.5 exposure (73.61 μg/m3 for 6 h/day, 7 days/week)	Gestation	Mouse	Left ventricular remodeling and dysfunction, inflammation, fibrosis, altered calcium homeostasis at 3 months of age	Effects only observed in male mice	[21]
Pb exposure (0.2% in maternal drinking water)	Post-natal days 1–21 (birth until weaning)	Rat	Increased total cholesterol, LDL and triglycerides at 4 and 18 months of age; necrosis, immune cell infiltration at 4 and 18 months of age	Only male offspring were evaluated	[22]
Pb exposure	Measured in prenatal maternal toenail samples	Human	Increased risk of elevated systolic blood pressure in young children (average 5.5 years of age)	Effects were stronger among boys	[23]
Cadmium exposure (0, 1, and 50 ppm)	Gestation	Mouse	Increased relative heart weight at birth in both sexes, increased risk of hypertension in females at 6 months of age	Yes	[24]
DEHP (250 mg/kg, 500 mg/kg, and 1 g/kg)	Embryonic day E6.5 to E14.5	Mouse	Increased cardiac malformations (septal defects, ventricular myocardium noncompaction, and cardiac hypoplasia) at E15.5—potentially secondary to maternal toxicity and weight loss	Not reported	[25]
Phthalates and alkylphenolic compounds	Maternal occupational exposure assessed via job exposure matrix	Human	Increased incidence of congenital heart defects, particularly in children who also carried ABCB1 polymorphism	Not reported	[26]
PFAS (PFOA and PFHxS)	Gestation (maternal serum and cord blood)	Human	Increased cardiometabolic risk score (insulin, waist circumference, and blood pressure) in adolescence	No sex differences were detected	[27]
DDT	Gestation (maternal serum samples)	Human	DDT exposure associated with hypertension at 39–47 years of age	Only females were evaluated	[28]
Diethylstilbestrol	Gestation	Human	Increased incidence of coronary artery disease and myocardial infarction	Only females were evaluated	[29]