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. 2018 May 3;99(5):922–937. doi: 10.1093/biolre/ioy109

Table 1.

Published preterm birth mouse models.

Stimulant
Type of model Targeted mutation Mouse strain Expected gestational length (days)a Breeding method Defined start of pregnancyb Treatment/ experimental manipulation Routec and concentration Day of injection Preterm delivery definition Term delivery definition in paper Pup survival Reference
Infection
N/A CD-1 19–20 ND Vaginal plug; dpc not defined E. coli 2 – 10 × 105 IU/IP 14.5 dpc Within 48 h ND None [31]
N/A C3H/HeN x C3H/HeN C3H/HeN x B6D2F1 BALB/c x B6D2F1 19–20 ND Vaginal plug and spermatozoa in vaginal smear at 0.0 dpc LPS serotype 055:B5 IP - 50 or 100 μg/kg (one injection) Or 50 μg/kg (two injections) 12, 15, or 17 dpc <19 dpc 19–20 dpc None [32]
N/A CD-1 ND ND Vaginal plug at 0.0 dpc LPS serotypes 0111:B4, 055:B5, 0127:B8*, and 0128:B12 IU 20 μg in 25 μl 16 dpc 36 h postinjection 60 ± 15 h postinjection LPS 0111:B4 none 055:B5 80% 0127:B8 95% 0128:B12 100% [33]
TLR-4 mutant CD-1 C3H/HeJ 19–20 Timed pregnant (supplier) ND LPS serotype L2280 (CD-1) L2880 and L4525 for TLR-4 mutant IU 250 μg/mouse (Sigma) 15 dpc At least 1 pup born < 48 h after LPS admin 19–20 dpc None [35]
C5aR−/− 129S4/SvJae ND Vaginal plug at 0 dpc No treatment, LPS serotype 055:B5 or RU486 250 μg LPS intravaginally SC 150 μg RU486 dissolved in DMSO 15 dpc Within 48 h postinjection 20–21 dpc ND [36]
N/A CD-1 19–20 ND Vaginal plug, dpc not defined TLR-2 ligand lipoteichoic acid, peptidoglycan, or TLR-3 ligand polyinosinic:cytidylic acid IU and IP 14.5 or 15.5 dpc At least 1 pup born or in lower vagina <48 h after surgery 19–20 dpc None [37]
N/A C3H/HeNCrj X Crj: B6D2F1 19–20 ND Vaginal plug and spermatozoa in the vaginal smear at 0.0 dpc Lipoteichoic acid IP 12.5–75 mg/kg single dose or repeated doses at 3h intervals 15 dpc 17 dpc <19.0 dpc 19–20 dpc None with doses given on 15 dpc 100% viable with doses given on 17 dpc [38]
N/A C57BL/6 19.5 ± 0.5 ND ND iE-DAP IP 500, 750, or 1000 μg in 200 μl PBS 14.5 dpc Delivery within 24 h postinjection ND ND [39]
N/A CD-1 ND Timed pregnant (supplier) ND Heat-killed GBS IP or IU 109 in 100 μl 14.5 dpc Within 48 h postinjection ND ND [42]
N/A C3H/HeN 19–20 ND Vaginal plug at 0.0 dpc Ureaplasmal outer membrane lipoprotein IU 15 μg 14.0 dpc Within 48 h ND ND [45]
N/A BALB/c (H-2d) 19–20 Overnight Vaginal plug at 0 dpc Chlamydia trachomatis mouse pneumonitis biovar (strain Nigg II) 101 to 107 inclusion-forming units in 20 μl of 0.2 M sucrose–20 mM sodium phosphate (pH 7.2)–5 mM glutamic acid 5 dpc ND 19.3 Maternal cannibalism precluded evaluation [47]
N/A C3H/HeJ 20 Timed-pregnant (supplier) ND E. coli Dr+ IH11128 and Dr14 Urethral catheterization into urinary bladder 7 dpc On or before 18 dpc ND 53.6% [50]
N/A C57Bl/6J 20.45 ND Vaginal plug at 0.0 dpc W83 strain of P. gingivalis 108 CFU 6 weeks before mating 17–18.25 dpc Delivery ND [55]
Faah–/–; Cnr–/– ND ∼19.8 ND Vaginal plug at 1.0 dpc LPS 0111:B4 IP 25 μg 16.0 dpc Before 19 dpc ∼19.8 dpc None [139]
N/A Kunming (derived from Swiss Webster) ND Overnight Vaginal plug at 0.0 dpc LPS serotype 0127 IP 150 μg/kg 15.5 dpc 15.5–17 dpc 18.0–20.0 dpc 47%d [140]
N/A CD-1 19–20 Overnight Vaginal plug at 0.0 dpc LPS serotype 0111 IU 10 μg 16.0 dpc 12.7 ± 7 h ND 14.6 ± 31% viable, but included deliveries 25–37 h after LPS [141]
N/A C57BL/6 19.5 ± 0.5 Overnight Vaginal plug at 0.5 dpc LPS IP 0.5 μg 16.5 dpc Before 18.0 dpc ND 2.3 fetuses per dam, may include term deliveries [142]
N/A C57BL/6 19.5 ± 0.5 ND Vaginal plug at 0.5 dpc LPS serotype 0111:B4 IA 100 ng/sac 16.5 dpc Before 18.0 dpc ND ND [143]
Uterine-specific p53 knockout FVB/129 ND C57BL/6-129 Overnight Vaginal plug at 1.0 dpc LPS IP 10 μg/ml 16.0 dpc Before 19 dpc ND 28% w/o LPS; 0% with LPS [84]
Inflammation
N/A C3H/Hel 20–21 Timed pregnant (supplier) ND Interleukin-1 SC 15–17 dpc Within 24 h 20–22 dpc ND [61]
N/A C57BL/6 19.5 ± 0.5 Overnight Vaginal plug at 0.5 dpc High-mobility group box-1 IA 9 ng 14.5 dpc 17.35 dpc 19.5 ± 0.5 dpc ∼85.4% viability; 60.9 ± 11.7% pup death by 1 week of age [64]
Cesarean
N/A CD-1 20 Overnight Vaginal plug at 1.0 dpc Cesarean NA NA On 18 or 19 dpc 20 dpc 0% (18 dpc) 87.8% (19 dpc) [65]
N/A CD-1 19–20 Timed pregnant (supplier) ND Cesarean NA NA 1 or 2 days before term Delivery 100% [144]
PPROM
N/A C57BL/6 19.5 ± 0.5 Pair mated (5 h) ND Fetal fibronectin Between fetal membranes and uterine lining (100–200 μg/ml) 17.0 dpc <18.5 dpc 19 dpc 20% [70]
Biglycan and Decorin double knockout C3H 19.5 Overnight Vaginal plug at 0.0 dpc NA NA NA Before 18.0 dpc 19.5 dpc 0% [67]
Early progesterone withdrawal
N/A C3H/HeN 19–20 Overnight Vaginal plug at 1.0 dpc Mifepristone (RU486) SC 50–250 μg 12–14 dpc Within 18 h 19–20 dpc 100% [75]
Prostaglandins
N/A C3H/HeN 19–20 Timed Pregnant (supplier) ND Prostaglandin F IP 20 μg 16 dpc Within 24 h <18 dpc ND [82]
15-hydroxy- prostaglandin dehydrogenase hypomorph C57BL/6-129/SvJ ∼19.3 ND Vaginal plug, dpc not defined NA NA NA Shorter gestation than control ∼19.3 dpc Equivalent to term [80]
Uterine quiescence
N/A CD-1 19 Timed pregnant (supplier) ND Tunicamycin IP 0–1 mg/kg 15 dpc 18–32 h postinjection 19 dpc Nonviable neonates at 16 and 17 dpc [89]
Endocannabinoid signaling
CB1 knockout C57BL/6J/129 ∼20.1 Overnight Vaginal plug at 1.0 dpc NA NA NA Before ∼19.5 dpc ∼20.1 dpc Yes [99]
Hyperhomocysteinemia
CBS knockout C57BL/6J 20.0 ± 0.2 Overnight Vaginal plug at 0.5 dpc NA NA NA At 16.6 ± 0.1 dpc 20.0 ± 0.2 dpc Yes [102]
Environmental effects
N/A C57BL/6 19.5 ± 0.5 Overnight Vaginal plug at 0.5 dpc 2,3,7,8-tetrachlo- rodibenzo-p-dioxin (dioxin) Mother was gavaged 10 μg/kg; no exposure as adult In utero at 15.5 dpc, none as adult 24 h before term 20 dpc Pups born preterm appeared viable at birth, died within 24 h Pups born at term survived [105]
N/A BL6C3F1 20.3 ± 0.2 Two days First day of pairing defined as 0.0 dpc Cigarette smoke diluted 90% Inhalation 2–18 dpc At 19.6 ± 0.2 dpc 20.3 ± 0.2 dpc Yes [145]
Other
N/A CD-1 19–20 Overnight Vaginal plug at 0 dpc L-arginine analog NG-nitro-L-arginine methyl ester (L-NAME) SC 0 (vehicle), 40, 70, or 100 mg L-NAME/kg in 10 ml/kg body weight 15.5 dpc and 16 dpc Before 18 dpc 18–19.5 dpc Maternal cannibalism precluded evaluation [107]
N/A CD-1 19–20 Overnight Vaginal plug at 0 dpc Methylene Blue SC 5, 30, 50, 60 or 85 mg/kg in 5 ml/kgb 15.5 dpc and 16 dpc Before 18 dpc 18–19.5 Appeared viable but maternal cannibalism precluded evaluation [108]
N/A ICR (CD-1) 19–20 Overnight Vaginal plug at 0.5 dpc Surfactant protein (SP)-A IA 3 μg in 50 μl per sac 15 dpc ND 19 dpc ND [109]
N/A BALB/C 20.2 ± 0.1 Overnight Vaginal plug at 0 dpc Neuromedin B IP 30, 90, or 150 μg/kg of NMB 18 dpc and 19 dpc at 1400 and 1800 h ND ND ND [110]
N/A C57Bl/6J 19.5 ± 0.5 ND Vaginal plug at 1 dpc Alcohol Intra-gastric 6 g/kg 17 dpc or 18 dpc 18.9 ± 0.1 dpc 19.5 ± 0.2 dpc 20.1 ± 0.1 ND [111]

aAs discussed by author or determined by [16]

bdpc, days postcoital

cIA, intraamniotic; IP, intraperitoneal; IU, intruterine; SC, subcutaneous

dincludes term deliveries

NA, not applicable

ND, not discussed

LPS, Lipopolysaccharide