Utero-placental calcium and magnesium ion channels: A systematic review of obstetric implications of their alterations.

Dysregulation of calcium and magnesium ion channels is linked to various adverse pregnancy outcomes, but more research is needed to understand the clinical implications fully.

Summary and findings

This systematic review synthesized data on the role of calcium and magnesium ion channels in uterine and placental functions, analyzing forty-nine studies. The review highlighted the dysregulation of these channels and their association with adverse pregnancy outcomes. Specific ion channels such as L-type and T-type voltage-gated Ca²⁺ channels were identified as key mediators.

Abstract

Despite the established roles of calcium (Ca²⁺) and magnesium (Mg²⁺) in placental function and uterine contractility, limited information exists on how dysregulation of major ion channels contributes to poor pregnancy outcomes. We synthesized data on the consequences of Ca²⁺ and Mg²⁺ channelopathies in uterine and placental functions. Using PubMed, Wiley Online, AJOL, and Web of Science databases for article search, a systematic review of forty-nine papers published between 2000 and March 2026 was carried out and reported in accordance with the PRISMA 2020 guideline. Based on the PICO framework, eligible studies involving human, animal, and in vitro designs were chosen and subjected to narrative analysis. L-type and T-type voltage-gated Ca²⁺ channels, together with transient receptor potential channels, emerged as principal mediators of placental Ca²⁺ transport and myometrial contractility. Mechanosensitive Piezo1 channels mediate stretch-activated Ca²⁺ influx, while store-operated Ca²⁺ entry pathways involving STIM1-Orai1 sustain intracellular Ca²⁺ homeostasis. Potassium-Ca²⁺ coupling channels modulated membrane hyperpolarization and anti-labor effects, and intracellular regulators such as PMCA and RYR1 fine-tuned Ca²⁺ homeostasis. The Mg²⁺ transporters are essential for preserving Mg²⁺ homeostasis and regulating Ca²⁺-dependent excitability. Dysregulation of these ion channel systems was consistently linked to abnormal uterine contractility, preterm birth, preeclampsia, fetal growth restriction, and adverse pregnancy outcomes. Both Ca²⁺ and Mg²⁺ ion channelopathies represent both a potential therapeutic target and a mechanistic factor underlying key obstetric complications.

Key findings

• Dysregulation of Ca²⁺ and Mg²⁺ ion channels linked to abnormal uterine contractility, preterm birth, preeclampsia, fetal growth restriction, and adverse pregnancy outcomes.
• Forty-nine papers published between 2000 and March 2026 were reviewed.
• L-type and T-type voltage-gated Ca²⁺ channels identified as principal mediators of placental Ca²⁺ transport.
• Mechanosensitive Piezo1 channels mediate stretch-activated Ca²⁺ influx.
• Store-operated Ca²⁺ entry pathways involving STIM1-Orai1 sustain intracellular Ca²⁺ homeostasis.

Limitations

• Narrative analysis without quantitative data.
• Potential biases in included studies.
• No specific effect sizes reported.
• Not all studies may have controlled for confounding factors.

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