HIV antiretroviral exposure in pregnancy induces detrimental placenta vascular changes that are rescued by progesterone supplementation
Abstract Adverse birth outcomes are common in HIV-positive pregnant women receiving combination antiretroviral therapy (cART), especially when cART is initiated in early pregnancy. The mechanisms remain poorly understood. Using a mouse model we demonstrate that protease inhibitor based-cART exposure...
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Nature Portfolio
2018
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oai:doaj.org-article:37bf226f60dd4bb08d817725f3d259132021-12-02T15:09:00ZHIV antiretroviral exposure in pregnancy induces detrimental placenta vascular changes that are rescued by progesterone supplementation10.1038/s41598-018-24680-w2045-2322https://doaj.org/article/37bf226f60dd4bb08d817725f3d259132018-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-24680-whttps://doaj.org/toc/2045-2322Abstract Adverse birth outcomes are common in HIV-positive pregnant women receiving combination antiretroviral therapy (cART), especially when cART is initiated in early pregnancy. The mechanisms remain poorly understood. Using a mouse model we demonstrate that protease inhibitor based-cART exposure beginning on day 1 of pregnancy was associated with a pro-angiogenic/pro-branching shift in the placenta driven by lower Flt-1 levels and higher Gcm-1 expression. Micro-CT imaging revealed an increase in the number of arterioles in cART-treated placentas, which correlated with fetal growth restriction. Delaying initiation of cART, or supplementing cART-treated mice with progesterone, prevented the pro-angiogenic/pro-branching shift and the associated placenta vascular changes. In agreement with our mouse findings, we observed an increase in the number of terminal-villi capillaries in placentas from HIV-positive cART-exposed women compared to HIV-negative controls. Capillary number was inversely correlated to maternal progesterone levels. Our study provides evidence that cART exposure during pregnancy influences placenta vascular formation that may in turn contribute to fetal growth restriction. Our findings highlight the need for closer investigation of the placenta in HIV-positive pregnancies, particularly for pregnancies exposed to cART from conception, and suggest that progesterone supplementation could be investigated as a possible intervention to improve placenta function in HIV-positive pregnant women.Hakimeh MohammadiEszter PappLindsay CahillMonique RennieNicole BankoLakmini PinnaduwageJanice LeeMark KibschullCaroline DunkJohn G. SledLena SerghidesNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-14 (2018) |
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Medicine R Science Q |
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Medicine R Science Q Hakimeh Mohammadi Eszter Papp Lindsay Cahill Monique Rennie Nicole Banko Lakmini Pinnaduwage Janice Lee Mark Kibschull Caroline Dunk John G. Sled Lena Serghides HIV antiretroviral exposure in pregnancy induces detrimental placenta vascular changes that are rescued by progesterone supplementation |
| description |
Abstract Adverse birth outcomes are common in HIV-positive pregnant women receiving combination antiretroviral therapy (cART), especially when cART is initiated in early pregnancy. The mechanisms remain poorly understood. Using a mouse model we demonstrate that protease inhibitor based-cART exposure beginning on day 1 of pregnancy was associated with a pro-angiogenic/pro-branching shift in the placenta driven by lower Flt-1 levels and higher Gcm-1 expression. Micro-CT imaging revealed an increase in the number of arterioles in cART-treated placentas, which correlated with fetal growth restriction. Delaying initiation of cART, or supplementing cART-treated mice with progesterone, prevented the pro-angiogenic/pro-branching shift and the associated placenta vascular changes. In agreement with our mouse findings, we observed an increase in the number of terminal-villi capillaries in placentas from HIV-positive cART-exposed women compared to HIV-negative controls. Capillary number was inversely correlated to maternal progesterone levels. Our study provides evidence that cART exposure during pregnancy influences placenta vascular formation that may in turn contribute to fetal growth restriction. Our findings highlight the need for closer investigation of the placenta in HIV-positive pregnancies, particularly for pregnancies exposed to cART from conception, and suggest that progesterone supplementation could be investigated as a possible intervention to improve placenta function in HIV-positive pregnant women. |
| format |
article |
| author |
Hakimeh Mohammadi Eszter Papp Lindsay Cahill Monique Rennie Nicole Banko Lakmini Pinnaduwage Janice Lee Mark Kibschull Caroline Dunk John G. Sled Lena Serghides |
| author_facet |
Hakimeh Mohammadi Eszter Papp Lindsay Cahill Monique Rennie Nicole Banko Lakmini Pinnaduwage Janice Lee Mark Kibschull Caroline Dunk John G. Sled Lena Serghides |
| author_sort |
Hakimeh Mohammadi |
| title |
HIV antiretroviral exposure in pregnancy induces detrimental placenta vascular changes that are rescued by progesterone supplementation |
| title_short |
HIV antiretroviral exposure in pregnancy induces detrimental placenta vascular changes that are rescued by progesterone supplementation |
| title_full |
HIV antiretroviral exposure in pregnancy induces detrimental placenta vascular changes that are rescued by progesterone supplementation |
| title_fullStr |
HIV antiretroviral exposure in pregnancy induces detrimental placenta vascular changes that are rescued by progesterone supplementation |
| title_full_unstemmed |
HIV antiretroviral exposure in pregnancy induces detrimental placenta vascular changes that are rescued by progesterone supplementation |
| title_sort |
hiv antiretroviral exposure in pregnancy induces detrimental placenta vascular changes that are rescued by progesterone supplementation |
| publisher |
Nature Portfolio |
| publishDate |
2018 |
| url |
https://doaj.org/article/37bf226f60dd4bb08d817725f3d25913 |
| work_keys_str_mv |
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