What question did this study set out to answer?

The study aims to uncover the mechanisms by which perinatal nicotine exposure affects cardiac health and its transgenerational effects.

March 26, 2026

Perinatal Nicotine Exposure–Induced Cardiac Phenotype Is Mediated by miR ‐1‐ MIAT Interaction and Is Transmitted Transgenerationally

Key Result

Perinatal nicotine exposure increases cardiac extracellular matrix deposition across multiple generations by upregulating MIAT and CTGF while suppressing miR-1.

Key Points

The study aims to uncover the mechanisms by which perinatal nicotine exposure affects cardiac health and its transgenerational effects.
Pregnant rats were exposed to nicotine or placebo until postnatal day 21.
F1 offspring were bred to produce F2 and F3 without further nicotine exposure.
Expression of miR-1, MIAT, and CTGF was assessed using qRT-PCR and immunoblotting.
Luciferase reporter assays and RNA immunoprecipitation analyzed miR-1 and MIAT interactions.
Perinatal nicotine increased CTGF and MIAT expression while decreasing miR-1 in both F1 and F3 heart tissues.
MIAT acted as a sponge for miR-1, inhibiting its function.
Induction of miR-1 reduced CTGF levels, indicating a regulatory pathway affected by nicotine.

Structured PICO

Does perinatal nicotine exposure alter the MIAT/miR-1/CTGF axis and induce a transgenerational cardiac phenotype in rats?

Population

Pregnant Sprague-Dawley dams, their F1-F3 offspring, and cultured neonatal primary rat cardiac fibroblasts

Intervention

Perinatal nicotine exposure (until postnatal day 21)

Comparator

Placebo

Outcome

Expression of MIAT, miR-1, and CTGF in hearts at postnatal day 21surrogate

Perinatal nicotine exposure induces a transgenerational cardiac fibrotic phenotype in rats mediated by the MIAT/miR-1/CTGF axis.

Main Result

Absolute Event Rate: 0% vs 0%

Abstract

Cardiac fibrosis in perinatally nicotine-exposed hearts has been demonstrated, but the underlying mechanisms remain unclear. Moreover, whether this phenotype is transmitted transgenerationally, as has been shown for perinatal nicotine exposure-induced asthma, is not known. MicroRNA (miR)-1, which targets a key extracellular matrix (ECM) protein, connective tissue growth factor (CTGF), and myocardial infarction-associated transcript (MIAT), a long noncoding RNA, are implicated in cardiac injury. We hypothesized that perinatal nicotine exposure alters the MIAT/miR-1/CTGF axis in rat hearts in a transgenerational manner. Pregnant Sprague-Dawley dams received nicotine or a placebo until postnatal day (PND) 21. Some F1 offspring were bred to produce F2, which were then bred to generate F3 progeny, with no further nicotine exposure beyond the F0 generation. Hearts from F1 and F3 pups were analyzed at PND21 for MIAT, miR-1, and CTGF expression by qRT-PCR and immunoblotting. Perinatal nicotine exposure upregulated CTGF and downregulated miR-1 while increasing MIAT expression in F1 and F3 hearts. MIAT was demonstrated to act as a sponge for miR-1 by luciferase reporter assay and RNA immunoprecipitation analysis. Gain-of-function of miR-1 decreased the expression of CTGF, whereas MIAT knockdown resulted in miR-1 induction, with a decrease in CTGF expression in cardiac fibroblasts. Nicotine treatment of cultured neonatal primary rat cardiac fibroblasts increased the expression of MIAT and CTGF while suppressing miR-1 levels. These data provide a novel mechanistic basis for increased cardiac ECM deposition following perinatal nicotine exposure and, for the first time, demonstrate the transgenerational transmission of perinatal nicotine-induced cardiac phenotype.

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