Attenuation of ductus arteriosus intimal thickening in preterm sheep twins compared with singletons
Preterm twins have a higher morbidity rate of patent ductus arteriosus (PDA) than do singletons. However, the effect of multiple births on maturation of the ductus arteriosus (DA) has not been reported. Because intimal thickening (IT) is required for DA anatomical closure, we examined IT development in the DA of preterm twins and singletons. Sheep DA tissues obtained from preterm fetuses were subjected to elastica van Gieson staining to evaluate IT. The total IT score in each DA was the sum of the IT scores obtained from six evenly divided parts of the DA, which was positively correlated with gestational ages in singletons. Total IT scores were smaller in preterm twins than in singletons, although no difference in gestational age, birth weight, or gender ratio was observed. These data suggest that IT development of the DA is attenuated in sheep preterm twins, which may affect the higher morbidity of PDA.
KeywordsDuctus arteriosus Intimal thickening Preterm infant Multiple births
The authors are grateful to Yuka Sawada for her technical assistance. We thank Megumi Fukui and Takashi Nakamura for technical advice on between-species differences in pregnancy physiology.
The authors’ contributions are as follows: SI, UY, SW, and TM initiated the project. SI, UY, and JS were involved in the design of the experiments. SI, UY, JS, SW, TM, SS, HU, RK, YM, MS, and TH conducted the experiments. SI and UY analyzed the data. JS supported the histological experiments. SI, UY, and YI wrote the manuscript. All authors discussed the results and commented on the paper.
Compliance with ethical standards
Conflict of interest
Satoko Ito, Utako Yokoyama, Junichi Saito, Shinichi Sato, Haruo Usuda, Shimpei Watanabe, Ryuta Kitanishi, Yuichiro Miura, Masatoshi Saito, Takushi Hanita, Tadashi Matsuda, and Yoshihiro Ishikawa declare that they have no conflict of interest.
This study was funded by MEXT/JSPS KAKENHI (SI, 43008732; UY, 16H05358, 15H05761; JS, 16H07107; YI, H1605300, 16K15205), and Yokohama Foundation for Advancement of Medical Science (JS), and the Japan Agency for Medical Research and Development (AMED) (YI, 66890011, 66890023, 17ek0109240h0001, A261TS).
All applicable international, national, and institutional guidelines for the care and use of animals were followed.
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