PMID- 33933084
OWN - NLM
STAT- MEDLINE
DCOM- 20210830
LR  - 20210830
IS  - 1746-6148 (Electronic)
IS  - 1746-6148 (Linking)
VI  - 17
IP  - 1
DP  - 2021 May 1
TI  - Fetal hypoxia and apoptosis following maternal porcine reproductive and 
      respiratory syndrome virus (PRRSV) infection.
PG  - 182
LID - 10.1186/s12917-021-02883-0 [doi]
LID - 182
AB  - BACKGROUND: Mechanisms of fetal death following maternal PRRSV2 infection remain 
      uncharacterized, although hypoxia from umbilical cord lesions and/or placental 
      detachment due to apoptosis are hypothesized. We performed two experiments 
      examining hypoxia and apoptosis in PRRSV-infected and non-infected, 
      third-trimester fetuses to elucidate possible associations with fetal death. 
      Fetuses were selected based on four phenotypic infection groups: fetuses from 
      non-challenged control gilts (CTRL); low viral load fetuses (LVL; Exp 1) or 
      uninfected fetuses (UNINF; Exp 2) from inoculated gilts; viable high viral load 
      fetuses (HVL-VIA); and HVL meconium-stained fetuses (HVL-MEC). RESULTS: In 
      experiment 1, paraffin embedded fetal tissues collected 21 days post maternal 
      infection (DPI) were examined for DNA fragmentation associated with apoptosis. 
      Positively stained foci were larger and more numerous (P < 0.05) in heart, liver, 
      and thymus of HVL-VIA and HVL-MEC compared to CTRL and LVL fetuses. In experiment 
      2, group differences in gene expression within the hypoxia (HIF1a, IDO1, VEGFa, 
      LDHA, NOS2, NOX1) and apoptosis (CASP3, CASP7, CASP8, CASP9, RIPK1, RIPK3) 
      pathways were assessed by RT-qPCR in fetal tissues collected at 12 DPI. High 
      viral load fetuses showed differential expression relative to the CTRL and UNINF 
      (P < 0.05 for all). Brain tissue from HVL-VIA and HVL-MEC fetuses presented 
      increased expression of CASP7, CASP8, RIPK3, HIF1a and IDO1. Fetal heart showed 
      increased expression of CASP8, HIF1a, IDO and NOX1 and a decrease in NOS2 
      expression in infected groups. CASP7, CASP9, RIPK1 and RIPK3 were only increased 
      in the heart of HVL-VIA while VEGFa was only increased for HVL-MEC fetuses. 
      Thymus from HVL-MEC had decreased expression of CASP9 and there was increased 
      IDO1 in all infected fetuses. CONCLUSIONS: There is strong evidence of apoptosis 
      occurring in the heart, liver and thymus of highly viral load fetuses at 21 DPI. 
      Furthermore, there was clear upregulation of apoptotic genes in the heart of high 
      viral load infected fetuses and less prominent upregulation in the brain of 
      PRRSV-infected fetuses, whereas thymus appears to be spared at 12 DPI. There was 
      no strong evidence of hypoxia at 12 DPI in brain and thymus but some indication 
      of hypoxia occurring in fetal heart.
FAU - Malgarin, Carolina M
AU  - Malgarin CM
AD  - Western College of Veterinary Medicine, Saskatoon, 52 Campus Dr, Saskatoon, 
      Saskatchewan, S7N 5B4, Canada.
FAU - Moser, Fiona
AU  - Moser F
AD  - Western College of Veterinary Medicine, Saskatoon, 52 Campus Dr, Saskatoon, 
      Saskatchewan, S7N 5B4, Canada.
FAU - Pasternak, J Alex
AU  - Pasternak JA
AD  - Western College of Veterinary Medicine, Saskatoon, 52 Campus Dr, Saskatoon, 
      Saskatchewan, S7N 5B4, Canada.
AD  - Department of Animal Science, Purdue University, West Lafayette, USA.
FAU - Hamonic, Glenn
AU  - Hamonic G
AD  - Western College of Veterinary Medicine, Saskatoon, 52 Campus Dr, Saskatoon, 
      Saskatchewan, S7N 5B4, Canada.
FAU - Detmer, Susan E
AU  - Detmer SE
AD  - Western College of Veterinary Medicine, Saskatoon, 52 Campus Dr, Saskatoon, 
      Saskatchewan, S7N 5B4, Canada.
FAU - MacPhee, Daniel J
AU  - MacPhee DJ
AD  - Western College of Veterinary Medicine, Saskatoon, 52 Campus Dr, Saskatoon, 
      Saskatchewan, S7N 5B4, Canada.
FAU - Harding, John C S
AU  - Harding JCS
AD  - Western College of Veterinary Medicine, Saskatoon, 52 Campus Dr, Saskatoon, 
      Saskatchewan, S7N 5B4, Canada. john.harding@usask.ca.
LA  - eng
PT  - Journal Article
DEP - 20210501
PL  - England
TA  - BMC Vet Res
JT  - BMC veterinary research
JID - 101249759
SB  - IM
MH  - Animals
MH  - *Apoptosis
MH  - Brain/metabolism
MH  - Female
MH  - Fetal Hypoxia/*veterinary
MH  - Fetus/virology
MH  - Gene Expression
MH  - Myocardium/metabolism
MH  - Porcine Reproductive and Respiratory Syndrome/*pathology/virology
MH  - Porcine respiratory and reproductive syndrome virus
MH  - Pregnancy
MH  - Pregnancy Complications, Infectious/*veterinary/virology
MH  - Sus scrofa
MH  - Swine
MH  - Thymus Gland/metabolism
MH  - Viral Load/veterinary
PMC - PMC8088663
OTO - NOTNLM
OT  - Apoptosis
OT  - Fetus
OT  - Gene expression
OT  - Hypoxia
OT  - PRRS
OT  - Swine
OT  - TUNEL
COIS- The authors declare no conflicts of interest with respect to the research, 
      authorship and/or publication of this article.
EDAT- 2021/05/03 06:00
MHDA- 2021/08/31 06:00
PMCR- 2021/05/01
CRDT- 2021/05/02 20:28
PHST- 2020/11/26 00:00 [received]
PHST- 2021/04/14 00:00 [accepted]
PHST- 2021/05/02 20:28 [entrez]
PHST- 2021/05/03 06:00 [pubmed]
PHST- 2021/08/31 06:00 [medline]
PHST- 2021/05/01 00:00 [pmc-release]
AID - 10.1186/s12917-021-02883-0 [pii]
AID - 2883 [pii]
AID - 10.1186/s12917-021-02883-0 [doi]
PST - epublish
SO  - BMC Vet Res. 2021 May 1;17(1):182. doi: 10.1186/s12917-021-02883-0.