Bæk Ole, Cilieborg Malene Skovsted, Nguyen Duc Ninh, Bering Stine Brandt, Thymann Thomas, Sangild Per Torp
Comparative Pediatrics and Nutrition, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg, Denmark.
Department of Neonatology, Rigshospitalet, Copenhagen, Denmark.
Front Pediatr. 2021 Feb 11;9:626101. doi: 10.3389/fped.2021.626101. eCollection 2021.
After very preterm birth, male infants show higher mortality than females, with higher incidence of lung immaturity, neurological deficits, infections, and growth failure. In modern pig production, piglets dying in the perinatal period (up to 20%) often show signs of immature organs, but sex-specific effects are not clear. Using preterm pigs as model for immature infants and piglets, we hypothesized that neonatal survival and initial growth and immune development depend on sex. Using data from a series of previous intervention trials with similar delivery and rearing procedures, we established three cohorts of preterm pigs (90% gestation), reared for 5, 9, or 19 days before sample collection (total = 1,938 piglets from 109 litters). Partly overlapping endpoints among experiments allowed for multiple comparisons between males and females for data on mortality, body and organ growth, gut, immunity, and brain function. Within the first 2 days, males showed higher mortality than females (18 vs. 8%, < 0.001), but less severe immune response to gram-positive infection. No effect of sex was observed for thermoregulation or plasma cortisol. Later, infection resistance did not differ between sexes, but growth rate was reduced for body (up to -40%) and kidneys (-6%) in males, with higher leucocyte counts (+15%) and lower CD4 T cell fraction (-5%) on day 9 and lower monocyte counts (-18%, day 19, all < 0.05). Gut structure, function and necrotizing enterocolitis (NEC) incidence were similar between groups, but intestinal weight (-3%) and brush-border enzyme activities were reduced at day 5 (lactase, DPP IV, -8%) in males. Remaining values for blood biochemistry, hematology, bone density, regional brain weights, and visual memory (tested in a T maze) were similar. Following preterm birth, male pigs show higher mortality and slower growth than females, despite limited differences in organ growth, gut, immune, and brain functions. Neonatal intensive care procedures may be particularly important for compromised newborns of the male sex. Preterm pigs can serve as good models to study the interactions of sex- and maturation-specific survival and physiological adaptation in mammals.
极早早产出生后，男婴死亡率高于女婴，肺部不成熟、神经功能缺陷、感染及生长发育迟缓的发生率更高。在现代养猪生产中，围产期死亡的仔猪（高达20%）常表现出器官不成熟的迹象，但性别特异性影响尚不清楚。以早产猪作为未成熟婴儿和仔猪的模型，我们推测新生儿存活、初始生长及免疫发育取决于性别。利用一系列先前具有相似分娩和饲养程序的干预试验数据，我们建立了三组早产猪队列（妊娠90%），在样本采集前分别饲养5天、9天或19天（共109窝1938头仔猪）。实验间部分重叠的终点指标使得能够对雄性和雌性在死亡率、身体和器官生长、肠道、免疫及脑功能数据方面进行多次比较。在出生后的头2天内，雄性仔猪死亡率高于雌性（18%对8%，<0.001），但对革兰氏阳性菌感染的免疫反应较轻。在体温调节或血浆皮质醇方面未观察到性别差异。之后，两性的抗感染能力无差异，但雄性仔猪的身体（高达-40%）和肾脏（-6%）生长速率降低，在第9天白细胞计数较高（+15%），CD4 T细胞比例较低（-5%），在第19天单核细胞计数较低（-18%，均<0.05）。各组间肠道结构、功能及坏死性小肠结肠炎（NEC）发生率相似，但雄性仔猪在第5天时肠道重量（-3%）及刷状缘酶活性降低（乳糖酶、二肽基肽酶IV，-8%）。血液生化、血液学、骨密度、脑区重量及视觉记忆（在T迷宫中测试）的其余数值相似。极早早产出生后，雄性仔猪尽管在器官生长、肠道、免疫及脑功能方面差异有限，但死亡率高于雌性，生长也更缓慢。新生儿重症监护程序对受损的雄性新生儿可能尤为重要。早产猪可作为研究哺乳动物性别和成熟特异性存活及生理适应相互作用的良好模型。
