Single nucleotide polymorphisms in surfactant protein A1 are not associated with a lack of responsiveness to antenatal steroid therapy in a pregnant sheep model
Abstract Treatment with antenatal steroids (ANS) is standard practice for reducing the risk of respiratory distress in the preterm infant. Despite clear overall benefits when appropriately administered, many fetuses fail to derive benefit from ANS therapies. In standardized experiments using a pregn...
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| Format: | Article |
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Wiley
2022-10-01
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| Series: | Physiological Reports |
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| Online Access: | https://doi.org/10.14814/phy2.15477 |
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| author | Tsukasa Takahashi Yuki Takahashi Erin L. Fee Haruo Usuda Lucy Furfaro John P. Newnham Alan H. Jobe Matthew W. Kemp |
| author_facet | Tsukasa Takahashi Yuki Takahashi Erin L. Fee Haruo Usuda Lucy Furfaro John P. Newnham Alan H. Jobe Matthew W. Kemp |
| author_sort | Tsukasa Takahashi |
| collection | DOAJ |
| description | Abstract Treatment with antenatal steroids (ANS) is standard practice for reducing the risk of respiratory distress in the preterm infant. Despite clear overall benefits when appropriately administered, many fetuses fail to derive benefit from ANS therapies. In standardized experiments using a pregnant sheep model, we have demonstrated that around 40% of ANS‐exposed lambs did not have functional lung maturation significantly different from that of saline‐treated controls. Surfactant protein A is known to play an important role in lung function. In this genotyping study, we investigated the potential correlation between polymorphisms in SFTPA1, messenger RNA and protein levels, and ventilation outcomes in animals treated with ANS. 45 preterm lambs were delivered 48 h after initial ANS therapy and 44 lambs were delivered 8 days after initial ANS therapy. The lambs were ventilated for 30 min after delivery. SFTPA1 mRNA expression in lung tissue was not correlated with arterial blood PaCO2 values at 30 min of ventilation in lambs delivered 48 h after treatment. SFTPA1 protein in lung tissue was significantly correlated with PaCO2 at 30 min of ventilation in lambs ventilated both 48 h and 8 days after ANS treatment. Six different single nucleotide polymorphisms (SNPs) in the Ovis aries SFTPA1 sequence were detected by Sanger Sequencing. No individual SNPs or SNP haplotypes correlated with alterations in PaCO2 at 30 min of ventilation or SFTPA1 protein levels in the lung. For the subset of animals analyzed in the present study, variable lung maturation responses to ANS therapy were not associated with mutations in SFTPA1. |
| first_indexed | 2024-03-08T23:56:44Z |
| format | Article |
| id | doaj.art-605e84a87d7f4b908a1899bdf64c37aa |
| institution | Directory Open Access Journal |
| issn | 2051-817X |
| language | English |
| last_indexed | 2024-03-08T23:56:44Z |
| publishDate | 2022-10-01 |
| publisher | Wiley |
| record_format | Article |
| series | Physiological Reports |
| spelling | doaj.art-605e84a87d7f4b908a1899bdf64c37aa2023-12-13T02:36:08ZengWileyPhysiological Reports2051-817X2022-10-011019n/an/a10.14814/phy2.15477Single nucleotide polymorphisms in surfactant protein A1 are not associated with a lack of responsiveness to antenatal steroid therapy in a pregnant sheep modelTsukasa Takahashi0Yuki Takahashi1Erin L. Fee2Haruo Usuda3Lucy Furfaro4John P. Newnham5Alan H. Jobe6Matthew W. Kemp7Division of Obstetrics and Gynaecology The University of Western Australia Perth Western Australia AustraliaDivision of Obstetrics and Gynaecology The University of Western Australia Perth Western Australia AustraliaDivision of Obstetrics and Gynaecology The University of Western Australia Perth Western Australia AustraliaDivision of Obstetrics and Gynaecology The University of Western Australia Perth Western Australia AustraliaDivision of Obstetrics and Gynaecology The University of Western Australia Perth Western Australia AustraliaDivision of Obstetrics and Gynaecology The University of Western Australia Perth Western Australia AustraliaDivision of Obstetrics and Gynaecology The University of Western Australia Perth Western Australia AustraliaDivision of Obstetrics and Gynaecology The University of Western Australia Perth Western Australia AustraliaAbstract Treatment with antenatal steroids (ANS) is standard practice for reducing the risk of respiratory distress in the preterm infant. Despite clear overall benefits when appropriately administered, many fetuses fail to derive benefit from ANS therapies. In standardized experiments using a pregnant sheep model, we have demonstrated that around 40% of ANS‐exposed lambs did not have functional lung maturation significantly different from that of saline‐treated controls. Surfactant protein A is known to play an important role in lung function. In this genotyping study, we investigated the potential correlation between polymorphisms in SFTPA1, messenger RNA and protein levels, and ventilation outcomes in animals treated with ANS. 45 preterm lambs were delivered 48 h after initial ANS therapy and 44 lambs were delivered 8 days after initial ANS therapy. The lambs were ventilated for 30 min after delivery. SFTPA1 mRNA expression in lung tissue was not correlated with arterial blood PaCO2 values at 30 min of ventilation in lambs delivered 48 h after treatment. SFTPA1 protein in lung tissue was significantly correlated with PaCO2 at 30 min of ventilation in lambs ventilated both 48 h and 8 days after ANS treatment. Six different single nucleotide polymorphisms (SNPs) in the Ovis aries SFTPA1 sequence were detected by Sanger Sequencing. No individual SNPs or SNP haplotypes correlated with alterations in PaCO2 at 30 min of ventilation or SFTPA1 protein levels in the lung. For the subset of animals analyzed in the present study, variable lung maturation responses to ANS therapy were not associated with mutations in SFTPA1.https://doi.org/10.14814/phy2.15477antenatal corticosteroidslung maturationpreterm birthsheepsingle nucleotide polymorphisms |
| spellingShingle | Tsukasa Takahashi Yuki Takahashi Erin L. Fee Haruo Usuda Lucy Furfaro John P. Newnham Alan H. Jobe Matthew W. Kemp Single nucleotide polymorphisms in surfactant protein A1 are not associated with a lack of responsiveness to antenatal steroid therapy in a pregnant sheep model Physiological Reports antenatal corticosteroids lung maturation preterm birth sheep single nucleotide polymorphisms |
| title | Single nucleotide polymorphisms in surfactant protein A1 are not associated with a lack of responsiveness to antenatal steroid therapy in a pregnant sheep model |
| title_full | Single nucleotide polymorphisms in surfactant protein A1 are not associated with a lack of responsiveness to antenatal steroid therapy in a pregnant sheep model |
| title_fullStr | Single nucleotide polymorphisms in surfactant protein A1 are not associated with a lack of responsiveness to antenatal steroid therapy in a pregnant sheep model |
| title_full_unstemmed | Single nucleotide polymorphisms in surfactant protein A1 are not associated with a lack of responsiveness to antenatal steroid therapy in a pregnant sheep model |
| title_short | Single nucleotide polymorphisms in surfactant protein A1 are not associated with a lack of responsiveness to antenatal steroid therapy in a pregnant sheep model |
| title_sort | single nucleotide polymorphisms in surfactant protein a1 are not associated with a lack of responsiveness to antenatal steroid therapy in a pregnant sheep model |
| topic | antenatal corticosteroids lung maturation preterm birth sheep single nucleotide polymorphisms |
| url | https://doi.org/10.14814/phy2.15477 |
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