Maternal Iron Deficiency Programs Rat Offspring Hypertension in Relation to Renin—Angiotensin System and Oxidative Stress

Abstract

Hypertension is an important public health challenge, affecting up to 30–50% of adults worldwide. Several epidemiological studies indicate that high blood pressure originates in fetal life—the so-called programming effect or developmental origin of hypertension. Iron-deficiency anemia has become one of the most prevalent nutritional problems globally. Previous animal experiments have shown that prenatal iron-deficiency anemia adversely affects offspring hypertension. However, the underlying mechanism remains unclear. We used a maternal low-iron diet Sprague Dawley rat model to study changes in blood pressure, the renal renin-angiotensin system, oxidative stress, inflammation, and sodium transporters in adult male offspring. Our study revealed that 16-week-old male offspring born to mothers with low dietary iron throughout pregnancy and the lactation period had (1) higher blood pressure, (2) increased renal cortex angiotensin II receptor type 1 and angiotensin-converting enzyme abundance, (3) decreased renal cortex angiotensin II receptor type 2 and MAS abundance, and (4) increased renal 8-hydroxy-2′-deoxyguanosine and interleukin-6 abundance. Improving the iron status of pregnant mothers could influence the development of hypertension in their offspring.

Iron Metabolism and Ferroptosis in Physiological and Pathological Pregnancy

“…Apart from supporting maternal hemoglobin synthesis, adequate iron concentration in utero is also essential for fetal development and helps build iron stores in early infancy [ 30 ]. Since iron deficiency has been associated with adverse maternal-fetal outcomes such as increased maternal morbidity, preterm birth, intrauterine growth restriction, and neurocognitive impairment in offspring, iron supplement during pregnancy is universally recommended [ 31 , 32 ].…”