Abstract
Urinary tract infections (UTI) during pregnancy are frequently associated with hypertensive disorders, increasing the risk of perinatal morbidity. Calcitriol, vitamin D3’s most active metabolite, has been involved in blood pressure regulation and prevention of UTIs, partially through modulating vasoactive peptides and antimicrobial peptides, like cathelicidin. However, nothing is known regarding the interplay between placental calcitriol, cathelicidin, and maternal blood pressure in UTI-complicated pregnancies. Here, we analyzed the correlation between these parameters in pregnant women with UTI and with normal pregnancy (NP). Umbilical venous serum calcitriol and its precursor calcidiol were significantly elevated in UTI. Regardless of newborn’s sex, we found strong negative correlations between calcitriol and maternal systolic and diastolic blood pressure in the UTI cohort (p < 0.002). In NP, this relationship was observed only in female-carrying mothers. UTI-female placentas showed higher expression of cathelicidin and CYP27B1, the calcitriol activating-enzyme, compared to male and NP samples. Accordingly, cord-serum calcitriol from UTI-female neonates negatively correlated with maternal bacteriuria. Cathelicidin gene expression positively correlated with gestational age in UTI and with newborn anthropometric parameters. Our results suggest that vitamin D deficiency might predispose to maternal cardiovascular risk and perinatal infections especially in male-carrying pregnancies, probably due to lower placental CYP27B1 and cathelicidin expression.
Highlights
During pregnancy, maternal cardiovascular and renal physiology undergo profound changes to favor adequate perfusion of the uteroplacental unit
Considering all of the above, we aimed to investigate whether there is an association between the placental production of calcitriol and maternal blood pressure in control pregnancies and those affected with
In the urinary tract infection (UTI) cohort, the newborn anthropometric parameters, Apgar scores, and gestational age at delivery were all significantly reduced as compared to normal pregnancies (NP)
Summary
Maternal cardiovascular and renal physiology undergo profound changes to favor adequate perfusion of the uteroplacental unit These changes include increased cardiac output, stroke volume, blood volume, and heart rate as well as the increment in the circulation of molecules that rise blood pressure and body-fluid volume, such as renin and angiotensin (ANG) II, which are components of the renin-angiotensin system (RAS) [1,2]. Disruption or dysregulation of the mechanisms involved in these processes may result in gestational hypertensive disorders, including preeclampsia, as shown when an excessive secretion of renin from placental origin is released into the maternal circulation [8,9] Calcitriol is another important placental factor that spills into the maternal circulation and modulates feto-maternal physiology [10,11,12]. Calcitriol is the hormonal form and most active metabolite of vitamin
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