Department of Infectious Diseases and Center for Tropical and Emerging Global Diseases, University of Georgia, Athens, GA, United States.
Department of Infectious Diseases and Immunology, University of Florida, Gainesville, FL, United States.
Sci Rep. 2019 Dec 20;9(1):19566. doi: 10.1038/s41598-019-55588-8.
Plasmodium falciparum infection during pregnancy is a major cause of severe maternal illness and neonatal mortality. Mouse models are important for the study of gestational malaria pathogenesis. When infected with Plasmodium chabaudi chabaudi AS in early gestation, several inbred mouse strains abort at midgestation. We report here that outbred Swiss Webster mice infected with P. chabaudi chabaudi AS in early gestation carry their pregnancies to term despite high parasite burden and malarial hemozoin accumulation in the placenta at midgestation, with the latter associated with induction of heme oxygenase 1 expression. Infection yields reduced fetal weight and viability at term and a reduction in pup number at weaning, but does not influence postnatal growth prior to weaning. This novel model allows for the exploration of malaria infection throughout pregnancy, modeling chronic infections observed in pregnant women prior to the birth of underweight infants and enabling the production of progeny exposed to malaria in utero, which is critical for understanding the postnatal repercussions of gestational malaria. The use of outbred mice allows for the exploration of gestational malaria in a genetically diverse model system, better recapitulating the diversity of infection responses observed in human populations.
疟原虫感染妊娠是严重的孕产妇疾病和新生儿死亡的主要原因。鼠模型是研究妊娠疟疾发病机制的重要工具。当感染早期妊娠的伯氏疟原虫时，几种近交系小鼠会在妊娠中期流产。我们在这里报告，即使在妊娠中期胎盘中有高寄生虫负担和疟原血红素积累的情况下，感染早期妊娠的伯氏疟原虫的瑞士 Webster 杂交鼠仍能将妊娠维持到足月，后者与诱导血红素加氧酶 1 表达有关。感染导致足月时胎儿体重和活力降低，断奶时幼鼠数量减少，但不影响断奶前的产后生长。这种新型模型允许在整个妊娠期间探索疟疾感染，模拟在出生体重不足的婴儿之前孕妇中观察到的慢性感染，并能够产生在子宫内暴露于疟疾的后代，这对于理解妊娠疟疾的产后影响至关重要。使用杂交鼠可以在遗传多样化的模型系统中探索妊娠疟疾，更好地重现人类人群中观察到的感染反应的多样性。
