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Oxytocin induced labor causes region and sex‐specific transient oligodendrocyte cell death in neonatal mouse brain
Author(s) -
Hirayama Takashi,
Hiraoka Yuichi,
Kitamura Eri,
Miyazaki Shinji,
Horie Kengo,
Fukuda Tomokazu,
Hidema Shizu,
Koike Masato,
Itakura Atsuo,
Takeda Satoru,
Nishimori Katsuhiko
Publication year - 2020
Publication title -
journal of obstetrics and gynaecology research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.597
H-Index - 50
eISSN - 1447-0756
pISSN - 1341-8076
DOI - 10.1111/jog.14149
Subject(s) - medicine , oxytocin , offspring , oligodendrocyte , immunostaining , brain damage , endocrinology , neuroscience , biology , pregnancy , central nervous system , immunohistochemistry , genetics , myelin
Aim Previous reports showed associations between oxytocin induced labor and mental disorders in offspring. However, those reports are restricted in epidemiological analyses and its mechanism remains unclear. In this study, we hypothesized that induced labor directly causes brain damage in newborns and results in the development of mental disorders. Therefore we aimed to investigate this hypothesis with animal model. Methods The animal model of induced labor was established by subcutaneous oxytocin administration to term‐pregnant C57BL/6J mice. We investigated the neonatal brain damage with evaluating immediate early gene expression ( c‐Fos, c‐Jun and JunB ) by quantitative polymerase reaction and TdT‐mediated dUTP nick end labeling staining. To investigate the injured brain cell types, we performed double‐immunostaining with TdT‐mediated dUTP nick end labeling staining and each brain component specific protein, such as Oligo2, NeuN, GFAP and Iba1. Results Brain damage during induced labor led to cell death in specific brain regions, which are implicated in mental disorders, in only male offspring at P0. Furthermore, oligodendrocyte precursors were selectively vulnerable compared to the other cell types. This oligodendrocyte‐specific impairment during the perinatal period led to an increased numbers of Olig2‐positive cells at P5. Expression levels of oxytocin and Oxtr in the fetal brain were not affected by the oxytocin administered to mothers during induced labor. Conclusion Oligodendrocyte cell death in specific brain regions, which was unrelated to the oxytocin itself, was caused by induced labor in only male offspring. This may be an underlying mechanism explaining the human epidemiological data suggesting an association between induced labor and mental disorders.