Prenatal Hypoxia Affects Foetal Cardiovascular Regulatory Mechanisms in a Sex- and Circadian-Dependent Manner: A Review

Abstract

Prenatal hypoxia during the prenatal period can interfere with the developmental trajectory and lead to developing hypertension in adulthood. Prenatal hypoxia is often associated with intrauterine growth restriction that interferes with metabolism and can lead to multilevel changes. Therefore, we analysed the effects of prenatal hypoxia predominantly not associated with intrauterine growth restriction using publications up to September 2021. We focused on: (1) The response of cardiovascular regulatory mechanisms, such as the chemoreflex, adenosine, nitric oxide, and angiotensin II on prenatal hypoxia. (2) The role of the placenta in causing and attenuating the effects of hypoxia. (3) Environmental conditions and the mother’s health contribution to the development of prenatal hypoxia. (4) The sex-dependent effects of prenatal hypoxia on cardiovascular regulatory mechanisms and the connection between hypoxia-inducible factors and circadian variability. We identified that the possible relationship between the effects of prenatal hypoxia on the cardiovascular regulatory mechanism may vary depending on circadian variability and phase of the days. In summary, even short-term prenatal hypoxia significantly affects cardiovascular regulatory mechanisms and programs hypertension in adulthood, while prenatal programming effects are not only dependent on the critical period, and sensitivity can change within circadian oscillations.

Indicators of Bioelectrical Activity of the Rat Heart After Prenatal Hypoxia and Pharmacological Correction

“…Angiolin is able, together with vitamin C, to form L-carnitine and normalize the work of mitochondria [21]. In our work, it was found that angiolin normalized the amplitudes of the ventricular R wave and the amplitude of the repolarization T wave under conditions of myocardial ischemia, which is associated with an improvement in the energy supply of the myocardium and a more rational use of macroergs to ensure the contractile function of the heart [12]. Angiolin increases the expression of HSP 70 , which "prolongs" the action of HIF-1a, and also independently maintains the expression of NAD-MDH-mx, thereby maintaining the activity of the compensatory mechanism of ATP productionthe malate-aspartate shuttle mechanism for a long time.…”

“…Our previous studies have obtained data indicating the role of the NO system in the formation of post hypoxic cardiomyopathy. So, in children who underwent intrauterine hypoxia, a deficiency of stable NO metabolites was found in blood against the background of eNOS inhibition [12].…”

“…The rats were kept under standard vivarium conditions at 20-25 С, humidity 50-55%, natural light, diet recommended for this species of laboratory animals, and water ad libitum. Here, we used the chronic hematic nitrite-induced PH model [11,12]. For a fixed term of pregnancy, mature male rats were placed with virgin female rats with a ratio of 2 males per 4 females.…”

Metabolic dysregulation and decreased capillarization in skeletal muscles of male adolescent offspring rats exposed to gestational intermittent hypoxia

“…In recent years, animal models of prenatal hypoxia have been widely used to understand the molecular mechanisms of adverse outcomes in offspring. Prenatal hypoxia affects fetal growth and elicits many disturbances after birth including the development of the central nervous system and cardiovascular regulatory system ( Peyronnet et al, 2000 ; Wang et al, 2021 ; Sutovska et al, 2022 ). Decreased oxygen supply and peripheral blood flow by gestational IH to the fetal organs such as the heart and brain have critical impacts on physiological functions of these organs ( Baschat et al, 1997 ).…”

Artificial Dim Light at Night during Pregnancy Can Affect Hormonal and Metabolic Rhythms in Rat Offspring

“…The circadian system develops “in utero” through exposure to maternal cues [ 20 , 21 ]. The importance of maternal–fetal communication is well known for other environmental factors such as nutrition, stress, and hypoxia, resulting in the development of diseases in adulthood [ 22 ]. The risk of maternal exposure to constant light during the second part of pregnancy has recently been underlined by the possibility that suppressed maternal melatonin can modify the epigenome of the fetal liver [ 23 , 24 ].…”