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. 2015 Feb 18;10(2):e0117978.
doi: 10.1371/journal.pone.0117978. eCollection 2015.

Differential mRNA expression and glucocorticoid-mediated regulation of TRPM6 and TRPM7 in the heart and kidney throughout murine pregnancy and development

James S M Cuffe  1 , Sarah Steane  1 , Karen M Moritz  1 , Tamara M Paravicini  1
Affiliations

Differential mRNA expression and glucocorticoid-mediated regulation of TRPM6 and TRPM7 in the heart and kidney throughout murine pregnancy and development

James S M Cuffe et al. PLoS One. .

Abstract

The transient receptor potential (TRP) channels TRPM6 and TRPM7 are critically involved in maintaining whole body and cellular Mg2+ homeostasis and ensuring the normal function of organs such as the heart and kidney. However, we do not know how the expression of TRPM6 and TPRM7 in these organs changes throughout fetal development and adult life, and whether this expression can be hormonally regulated. This study determined the ontogeny of TRPM6 and TRPM7 mRNA expression from mid-gestation through to adulthood in the mouse. In a second series of experiments, we examined how maternal administration of the glucocorticoids corticosterone and dexamethasone between embryonic days 12.5-15 affected TRPM6 and TRPM7 channel mRNA expression in the mother and fetus. Whilst renal TRPM7 expression was relatively constant throughout development, renal TRPM6 expression was markedly upregulated after birth. In contrast, cardiac TRPM7 expression was 2-4 fold higher in the fetus than in the adult. Surprisingly, TRPM6 expression was detected in the fetal heart (qPCR and in situ hybridization). Glucocorticoid administration during gestation increased fetal cardiac expression of both channels without affecting renal expression. In contrast, in the dam renal TRPM6 and TRPM7 expression was increased by glucocorticoids with no change in the cardiac channel expression. These data suggest that TRPM6 and TRPM7 channels are important in organogenesis, and that elevated maternal glucocorticoid levels can alter the expression of these channels. This suggests that perturbations in hormonal regulatory systems during pregnancy may adversely impact upon normal fetal development, at least in part by altering expression of TRPM channels.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Expression of TRPM6 and TRPM7 mRNA in the mouse kidney during development.
Expression of TRPM6 (A) and TRPM7 (B) mRNA (relative to 18S rRNA) in the kidneys of mice at embryonic days 14.5 and 17.5 (E14.5 and E17.5), postnatal day 30 (PN30), and adult male, female (Fem) and pregnant female (Fem+) animals. Data is expressed as mean ± SEM relative to the adult male, n = 5 (E14.5), 5 (E17.5), 9 (PN30), 5 (adult male), 5 (adult female), 5 (pregnant female). * P<0.05 vs E14.5 and E17.5; ** P<0.05 vs adult male.
Fig 2
Fig 2. Expression of TRPM6 and TRPM7 mRNA in the mouse heart during development.
Cardiac expression of TRPM6 (A) and TRPM7 (B) mRNA (relative to 18S rRNA) at embryonic days 14.5 and 17.5 (E14.5 and E17.5), postnatal day 30 (PN30), as well as in adult male, female (Fem) and pregnant female (Fem+). Data is expressed as mean ± SEM relative to the adult male, n = 5 (E14.5), 6 (E17.5), 9 (PN30), 6 (adult male), 5 (adult female), 4 (pregnant female). * P<0.05 vs E17.5.
Fig 3
Fig 3. Localization of TRPM6 and TRPM7 mRNA in the fetal heart.
In situ hybridization using antisense probes showing the localization of TRPM6 (A) and TRPM7 (C) in the fetal heart. Negative controls using the corresponding sense probes showed no staining for TRPM6 (B) or TRPM7 (D). RNA hybridization results in blue staining. All sections were counterstained using nuclear fast red. Scale bars represent 200 μM.
Fig 4
Fig 4. Localization of TRPM6 and TRPM7 mRNA in the adult kidney.
In situ hybridization using antisense probes showing the localization of TRPM6 (A) and TRPM7 (C) in the adult kidney. Negative controls using the corresponding sense probes showed no staining for TRPM6 (B) or TRPM7 (D) in the adult kidney. RNA hybridization results in blue staining. All sections were counterstained using nuclear fast red. Scale bars represent 100 μM.
Fig 5
Fig 5. Regulation of TRPM6 and TRPM7 in the fetal heart by glucocorticoids.
Expression of TRPM6 (top panels) and TRPM7 (bottom panels) mRNA (relative to 18S rRNA) in the fetal hearts of mice exposed to either corticosterone (Cort) or dexamethasone (Dex) for 60 hours during gestation. In panels A and C, expression was measured at embryonic day 14.5, immediately after glucocorticoid exposure. In panels B and D, expression was measured at embryonic day 17.5, ∼ 60 hours after the cessation of glucocorticoid treatment. Data is expressed as mean ± SEM relative to the saline control, n = 12 (E14.5 saline), 10 (E14.5 Cort), 12 (E14.5), 10 (E17.5 saline), 11 (E17.5 Cort), 4 (E17.5 Dex). * P<0.05 vs saline control.
Fig 6
Fig 6. Regulation of TRPM6 and TRPM7 in the maternal heart by glucocorticoids.
Expression of TRPM6 mRNA (relative to 18S rRNA) at 14.5 (A) and 17.5 (C) days of gestation, and TRPM7 mRNA at 14.5 (B) and 17.5 (D) days of gestation in the hearts of pregnant mice treated with either corticosterone (Cort) or dexamethasone (Dex) for 60 hours starting at gestational day 12.5. Data is expressed as mean ± SEM relative to the saline control, n = 4 (E14.5 saline), 5 (E14.5 Cort), 5 (E14.5 Dex), 5 (E17.5 saline), 5 (E17.5 Cort), 5 (E17.5 Dex).
Fig 7
Fig 7. Regulation of TRPM6 and TRPM7 in the fetal kidney by glucocorticoids.
Expression of TRPM6 (top panels) and TRPM7 (bottom panels) mRNA (relative to 18S rRNA) in the fetal kidneys of mice exposed to either corticosterone (Cort) or dexamethasone (Dex) for 60 hours during gestation. In panels A and C, expression was measured at embryonic day14.5, immediately after glucocorticoid exposure. In panels B and D, expression was measured at embryonic day 17.5, ∼ 60 hours after the cessation of glucocorticoid treatment. Data is expressed as mean ± SEM relative to the saline control, n = 11 (E14.5 saline), 8 (E14.5 Cort), 6 (E14.5 Dex), 6 (E17.5 saline), 6 (E17.5 Cort), 6 (E17.5 Dex).
Fig 8
Fig 8. Regulation of TRPM6 and TRPM7 in the maternal kidney by glucocorticoids.
Expression of TRPM6 mRNA (relative to 18S rRNA) at 14.5 (A) and 17.5 (C) days of gestation, and TRPM7 mRNA at 14.5 (B) and 17.5 (D) days of gestation in the kidneys of pregnant mice treated with either corticosterone (Cort) or dexamethasone (Dex) for 60 hours starting at gestational day 12.5. Data is expressed as mean ± SEM relative to the saline control, n = 7 (E14.5 saline), 5 (E14.5 Cort), 5 (E14.5 Dex), 5 (E17.5 saline 5), 5 (E17.5 Cort), 5 (E17.5 Dex).
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