ABCMdb

PMID: 18325992

Hodges CA, Palmert MR, Drumm ML
Infertility in females with cystic fibrosis is multifactorial: evidence from mouse models.
Endocrinology. 2008 Jun;149(6):2790-7. Epub 2008 Mar 6., [PubMed]

Sentences

No. Mutations Sentence Comment

36 ABCC7 p.Ser489* Materials and Methods Mouse strains The CF mouse models (Cftr-/- ) used in these studies contained either the Cftrtm1Unc mutation (referred to as the S489X mutation in this manuscript), which generates a stop codon in the coding region of exon 10 of Cftr (32) (Jackson Laboratory, Bar Harbor, ME; stock no. Login to comment 76 ABCC7 p.Ser489* Results Fertility in Cftr mutant females To determine the effect of the absence of Cftr on female fertility, two independently derived mouse models of CF (S489X and ⌬F508) and wild-type females were mated to wild-type males for 5 months and examined daily for subsequent birth of litters and number of pups. Login to comment 95 ABCC7 p.Ser489* Fertility of wild-type and Cftr mutant females Mouse type Mice, n Females with no litters, n (%) Average litter per month Average no. of pups/litter Wild type 18 0 (0) 0.92 Ϯ 0.13 6.56 Ϯ 2.36 ⌬F508 14 5 (35.7) 0.32 Ϯ 0.26a 3.81 Ϯ 1.43a S489X 10 2 (20) 0.36 Ϯ 0.36a 3.55 Ϯ 1.92a Both mutations 24 7 (29.2) 0.34 Ϯ 0.30a 3.70 Ϯ 1.61a a P Ͻ 0.001 vs. wild type. TABLE 2. Login to comment 96 ABCC7 p.Ser489* ABCC7 p.Ser489* Uterine and ovarian size in wild-type and Cftr mutant females Mouse type Mice, n Average ovarian weight (mg) Average uterine weight (mg) Average mouse weight (g) 6-8 wk Wild type 7 3.1 Ϯ 0.6 61.4 Ϯ 9.8 19.0 Ϯ 1.45 ⌬F508 6 1.4 Ϯ 0.2a 27.4 Ϯ 6.4a 16.4 Ϯ 1.59b S489X 6 1.8 Ϯ 0.6a 26.6 Ϯ 14.3a 15.9 Ϯ 1.46a Both mutations 12 1.6 Ϯ 0.5a 27.0 Ϯ 10.6a 16.1 Ϯ 1.48a 14-16 wk Wild type 11 4.2 Ϯ 1.1 74.8 Ϯ 11.8 21.6 Ϯ 1.92 ⌬F508 6 2.6 Ϯ 0.6a 45.8 Ϯ 20.5b 18.6 Ϯ 0.88a S489X 8 2.8 Ϯ 0.6a 50.6 Ϯ 17.1b 19.4 Ϯ 1.33a Both mutations 14 2.7 Ϯ 0.6a 48.2 Ϯ 18.2b 19.0 Ϯ 1.11a a P Ͻ 0.005 vs. wild type. Login to comment 123 ABCC7 p.Ser489* Wild-type and Cftr mutant females` response to exogenous hormones Mouse type Mice, na Average ovarian weight (mg) Average uterine weight (mg) Average mouse weight (g) Oocytes ovulated, n Wild type 10 7.3 Ϯ 2.3 110 Ϯ 10 21.5 Ϯ 3.08 24.3 Ϯ 9.62 ⌬F508 9 7.5 Ϯ 1.9 110 Ϯ 30 19.8 Ϯ 2.10b 24.2 Ϯ 7.87 S489X 6 6.0 Ϯ 1.7 92 Ϯ 14 19.4 Ϯ 1.85b 18.6 Ϯ 5.64 Both mutations 15 6.9 Ϯ 1.8 100 Ϯ 25 19.6 Ϯ 1.98b 22.2 Ϯ 7.47 a Ovulated oocytes were present in all injected females. Login to comment 125 ABCC7 p.Ser489* Characterization of estrous cycle in wild-type and Cftr mutant females Mouse type Mice, n Mice with no estrus, n (%) Total no. of estrus Avg no. of cycles/mousea Cycle lengtha Wild type 14 0 (0) 58 4.14 Ϯ 0.86 5.11 Ϯ 1.58 ⌬F508 18 4 (22.2) 29 2.07 Ϯ 1.20b 11.79 Ϯ 5.64b S489X 12 5 (41.7) 16 2.29 Ϯ 1.44b 11.19 Ϯ 6.29c Both mutations 30 9 (30.0) 45 2.14 Ϯ 1.28b 11.59 Ϯ 5.71b a Calculated using only females with at least one estrous cycle. Login to comment 156 ABCC7 p.Ser489* Fertilization of oocytes 48 h after hCG in wild-type and mutant females Mouse type (no. of mice) Total cells, n Cells at stage, % Oocyte One cell Two cell Three cell Four cell Wild type (4) 71 8.5 1.4 76.0 5.6 8.5 ⌬F508 (4) 63 98.4 0 1.6 0 0 S489X (4) 65 100 0 0 0 0 Both mutations 128 99.2 0 0.8 0 0 TABLE 6. Login to comment 157 ABCC7 p.Ser489* In vitro fertilization of oocytes from wild-type and Cftr mutant females Mouse type (no. of mice) Fertility rate (%)a Wild type (4) 49 of 72 (68.1) ⌬F508 (4) 52 of 74 (70.3) S489X (4) 46 of 68 (67.6) Both mutations (8) 98 of 142 (69.0) a Fertility rate is expressed as the number two-cell embryos over the total number of oocytes (percent). Login to comment 190 ABCC7 p.Ser489* Number of oviductal sperm and capacitation in wild-type and Cftr mutant females Mouse type (no. of mice) Total no. of sperm (average per oviduct) Capacitation (n ϭ 200 per mouse) (%) Wild type (3) 1536 Ϯ 291 100 ⌬F508 (3) 142 Ϯ 105a 100 S489X (3) 132 Ϯ 133a 100 Both mutations (6) 137 Ϯ 114a 100 a P Ͻ 0.001 vs. wild type. Login to comment