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Sex-Specific Survival, Growth, Immunity and Organ Development in Preterm Pigs as Models for Immature Newborns

Background: 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...

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Autores principales: Bæk, Ole, Cilieborg, Malene Skovsted, Nguyen, Duc Ninh, Bering, Stine Brandt, Thymann, Thomas, Sangild, Per Torp
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7905020/
https://www.ncbi.nlm.nih.gov/pubmed/33643975
http://dx.doi.org/10.3389/fped.2021.626101
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author Bæk, Ole
Cilieborg, Malene Skovsted
Nguyen, Duc Ninh
Bering, Stine Brandt
Thymann, Thomas
Sangild, Per Torp
author_facet Bæk, Ole
Cilieborg, Malene Skovsted
Nguyen, Duc Ninh
Bering, Stine Brandt
Thymann, Thomas
Sangild, Per Torp
author_sort Bæk, Ole
collection PubMed
description Background: 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. Methods: 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 n = 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. Results: Within the first 2 days, males showed higher mortality than females (18 vs. 8%, P < 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 P < 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. Conclusion: 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.
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spelling pubmed-79050202021-02-26 Sex-Specific Survival, Growth, Immunity and Organ Development in Preterm Pigs as Models for Immature Newborns Bæk, Ole Cilieborg, Malene Skovsted Nguyen, Duc Ninh Bering, Stine Brandt Thymann, Thomas Sangild, Per Torp Front Pediatr Pediatrics Background: 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. Methods: 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 n = 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. Results: Within the first 2 days, males showed higher mortality than females (18 vs. 8%, P < 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 P < 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. Conclusion: 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. Frontiers Media S.A. 2021-02-11 /pmc/articles/PMC7905020/ /pubmed/33643975 http://dx.doi.org/10.3389/fped.2021.626101 Text en Copyright © 2021 Bæk, Cilieborg, Nguyen, Bering, Thymann and Sangild. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pediatrics
Bæk, Ole
Cilieborg, Malene Skovsted
Nguyen, Duc Ninh
Bering, Stine Brandt
Thymann, Thomas
Sangild, Per Torp
Sex-Specific Survival, Growth, Immunity and Organ Development in Preterm Pigs as Models for Immature Newborns
title Sex-Specific Survival, Growth, Immunity and Organ Development in Preterm Pigs as Models for Immature Newborns
title_full Sex-Specific Survival, Growth, Immunity and Organ Development in Preterm Pigs as Models for Immature Newborns
title_fullStr Sex-Specific Survival, Growth, Immunity and Organ Development in Preterm Pigs as Models for Immature Newborns
title_full_unstemmed Sex-Specific Survival, Growth, Immunity and Organ Development in Preterm Pigs as Models for Immature Newborns
title_short Sex-Specific Survival, Growth, Immunity and Organ Development in Preterm Pigs as Models for Immature Newborns
title_sort sex-specific survival, growth, immunity and organ development in preterm pigs as models for immature newborns
topic Pediatrics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7905020/
https://www.ncbi.nlm.nih.gov/pubmed/33643975
http://dx.doi.org/10.3389/fped.2021.626101
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