# Prenatal Melatonin Modulates Cardiovascular Function and Oxidative Stress in Guinea Pig Neonates Under Normoxic and Hypoxic Gestation

**Authors:** Adolfo A. Paz, Tamara A. Jiménez, Pedro Herrera, Josefa Carreño, Damaris Cornejo, Julieta Ibarra-González, Javiera N. Ponce, Felipe A. Beñaldo, Mario Salamanca, Rodrigo Jeria, Esteban G. Figueroa, Alejandro González-Candia, Emilio A. Herrera

PMC · DOI: 10.3390/antiox15020162 · Antioxidants · 2026-01-25

## TL;DR

Prenatal melatonin helps reduce heart and blood vessel issues in guinea pig babies born to mothers exposed to low oxygen, but it may also cause unexpected changes in normal pregnancies.

## Contribution

This study shows prenatal melatonin can mitigate hypoxia-induced cardiovascular and oxidative stress effects in guinea pig neonates.

## Key findings

- Melatonin reversed hypoxia-induced endothelial dysfunction and oxidative stress in neonates.
- Melatonin increased catalase activity in hypoxic neonates, improving redox balance.
- Melatonin altered cardiac structure in normoxic pregnancies, increasing LV length and decreasing nuclei density.

## Abstract

Introduction: Gestational hypoxia (GH) increases the risk of cardiovascular diseases by inducing oxidative stress and vascular dysfunction. This study investigates whether prenatal melatonin can mitigate these effects in guinea pigs. Methods: Pregnant guinea pigs were exposed to normoxia or hypoxia and treated with melatonin (1 mg/kg/day). Echocardiography, vascular reactivity, and molecular assays were used to assess cardiovascular structure, function, and redox balance in neonates. Results: GH reduced neonatal birth weight and altered left ventricular (LV) development, resulting in increased LV systolic function and aortic blood flow velocity. Melatonin treatment reversed these effects, restoring endothelial-dependent vasodilation and decreasing oxidative stress in the LV and thoracic aorta. Catalase antioxidant enzyme activity was elevated in melatonin-treated hypoxic neonates. Unexpectedly, melatonin treatment altered cardiac structure in normoxic pregnancies, increasing LV length and decreasing LV myocardial nuclei density. Conclusions: Prenatal melatonin partially modulates GH-induced endothelial dysfunction and oxidative stress, offering potential therapeutic value. However, its effects under normoxic conditions deserve caution, emphasizing the need for targeted use only in pregnancies with evident hypoxic and oxidative stress conditions.

## Linked entities

- **Chemicals:** melatonin (PubChem CID 896)

## Full-text entities

- **Genes:** quinone oxidoreductase [NCBI Gene 100135507], SOD [NCBI Gene 100135623], HMOX1 [NCBI Gene 100715748], iNOS [NCBI Gene 100135576], CUL3 [NCBI Gene 100729326], Gpx4 [NCBI Gene 100730119], CAT [NCBI Gene 100135492], GSK-3beta [NCBI Gene 100714392], Dnmbp (dynamin binding protein) [NCBI Gene 71972] {aka 2410003L07Rik, 2410003M15Rik, TUBA}, GPX1 [NCBI Gene 100729115], GGH (gamma-glutamyl hydrolase) [NCBI Gene 8836] {aka GATD10, GH}, KEAP1 [NCBI Gene 100713871], Gpx2 [NCBI Gene 100714682], MT3 [NCBI Gene 100716374], INS (insulin) [NCBI Gene 3630] {aka IDDM, IDDM1, IDDM2, ILPR, IRDN, MODY10}, eNOS [NCBI Gene 100135577], RBX1 [NCBI Gene 100714763], HIF-1alpha [NCBI Gene 100713113], beta-Actin [NCBI Gene 100135470], Nfe2l2 (nuclear factor, erythroid derived 2, like 2) [NCBI Gene 18024] {aka Nrf2}, SOD1 [NCBI Gene 100135622], Gpx3 [NCBI Gene 100732539]
- **Diseases:** endothelial (MESH:D005642), overdose (MESH:D062787), hypertrophic (MESH:D002312), cardiac remodeling (MESH:D020257), cardiomegaly (MESH:D006332), cardiac dysfunction (MESH:D006331), CVDs (MESH:D002318), polydipsia (MESH:D059606), Vascular Dysfunction (MESH:D002561), placental insufficiency (MESH:D010927), OS (MESH:D000079225), deaths (MESH:D003643), hypertension (MESH:D006973), uterine artery occlusion (MESH:D001157), pregnancy complications (MESH:D011248), ventricular hypertrophy (MESH:D024741), GH (MESH:D000860), ventricular dilation (MESH:C566255), LV EDD (MESH:D018487), obesity (MESH:D009765), Hypoxic (MESH:D002534), gestational (MESH:D016640), Endothelial dysfunction (MESH:D014652), pre-eclampsia (MESH:D011225), injury to (MESH:D014947), FGR (MESH:D005317), volume overload (MESH:D019190)
- **Chemicals:** Tween 20 (MESH:D011136), eosin (MESH:D004801), KCl (MESH:D011189), H (MESH:D006859), DAB (MESH:C000469), N-acetylcysteine (MESH:D000111), sodium nitroprusside (MESH:D009599), formaldehyde (MESH:D005557), ROS (MESH:D017382), PO2 (MESH:C093415), SYBR Green (MESH:C098022), peroxynitrite (MESH:D030421), CO2 (MESH:D002245), GSH (MESH:D005978), citrate (MESH:D019343), lipid (MESH:D008055), HO- (MESH:D006695), alpha-tocopherol (MESH:D024502), catecholamine (MESH:D002395), heme (MESH:D006418), 2-mercaptoethanol (MESH:D008623), GSSG (MESH:D019803), H2O2 (MESH:D006861), Fe2+ (-), superoxide (MESH:D013481), hydrogen sulfide (MESH:D006862), H&amp;E (MESH:D006371), Melatonin (MESH:D008550), Bis (MESH:D001729), potassium (MESH:D011188), sodium citrate (MESH:D000077559), bis-acrylamide (MESH:C021221), hematoxylin (MESH:D006416), methacholine (MESH:D016210), glycerol (MESH:D005990), norepinephrine (MESH:D009638), 4-hydroxy-2-nonenal (MESH:C027576), ascorbic acid (MESH:D001205), SDS (MESH:D012967), acetic acid (MESH:D019342), NO (MESH:D009569), Acrylamide (MESH:D020106), EtOH (MESH:D000431), hydroxyl radical (MESH:D017665), water (MESH:D014867), phenol (MESH:D019800), luminal (MESH:D010634), iron (MESH:D007501), 3-NT (MESH:C002744), acetylcholine (MESH:D000109), TRIzol (MESH:C411644), Ponceau S (MESH:C032756), carbon monoxide (MESH:D002248), phenylephrine (MESH:D010656), lipoic acid (MESH:D008063), N (MESH:D009584), bromophenol blue (MESH:D001978), cortisol (MESH:D006854), EDTA (MESH:D004492), Triton X-100 (MESH:D017830)
- **Species:** Gallus gallus (bantam, species) [taxon 9031], Oryctolagus cuniculus (domestic rabbit, species) [taxon 9986], Cavia porcellus (domestic guinea pig, species) [taxon 10141], Rattus norvegicus (brown rat, species) [taxon 10116], Homo sapiens (human, species) [taxon 9606], Ovis aries (domestic sheep, species) [taxon 9940], Mus musculus (house mouse, species) [taxon 10090]
- **Mutations:** G8830A

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## References

102 references — full list in the complete paper: https://tomesphere.com/paper/PMC12937908/full.md

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Source: https://tomesphere.com/paper/PMC12937908