ArticleBiology of reproduction2010
Lack of functional pregnancy-associated plasma protein-A (PAPPA) compromises mouse ovarian steroidogenesis and female fertility.
Article in Biology of reproduction, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
39 citing papers in PubMed, 76 citations in OpenAlex.
- Pre-divergence hybridization and adaptive introgression shaped the genetic architecture of East Asian domestic pigs.Science China. Life sciences · 2026Article
- Bioinformatics analysis and differential tissue expression of the IGFBP4 gene in beef cattle.Protoplasma · 2026Article
- Population-Level Lambing Interval Patterns and Evaluation of Three Previously Reported Candidate SNPs in Hu and Tan Sheep.Animals : an open access journal from MDPI · 2026Article
- Genome-Wide Association Study of Daughter Pregnancy Rate in Crossbred Dairy Cows.International journal of molecular sciences · 2025Article
- PAPPA's role in female reproduction.Reproduction (Cambridge, England) · 2025Review
- Sex-specific DNA methylation associations with circulating urate levels and BCG-induced urate changes.Communications medicine · 2025Article
- Identification of IGFBP2 gene polymorphism and association of genotypes with performance traits in Large White Yorkshire pigs.Tropical animal health and production · 2025Article
- Review
- Characterizing the Role of Endocannabinoid Receptor Cnr1 in Mouse Ovarian Granulosa Cells.Cell biochemistry and function · 2025Article
- Landscape transcriptomic analysis of bovine follicular cells during key phases of ovarian follicular development.Biological research · 2024Article
- Unveiling the Role of IGF-I in Fertility: Effect of Long-Acting Bovine Somatotropin (bST) on Terminal Follicular Development and Fertility during an Annual Reproductive Cycle in Sheep.Animals : an open access journal from MDPI · 2024Article
- Effects of Cyanobacterial Harmful Algal Bloom Toxin Microcystin-LR on Gonadotropin-Dependent Ovarian Follicle Maturation and Ovulation in Mice.Environmental health perspectives · 2023Article
- Potential biomarkers to predict return to fertility after discontinuation of female contraceptives-looking to the future.Frontiers in reproductive health · 2023Review
- Global Transcriptional Profiling of Granulosa Cells from Polycystic Ovary Syndrome Patients: Comparative Analyses of Patients with or without History of Ovarian Hyperstimulation Syndrome Reveals Distinct Biomarkers and Pathways.Journal of clinical medicine · 2022Article
- The expression of IGFBP-5 in the reproductive axis and effect on the onset of puberty in female rats.Reproductive biology and endocrinology : RB&E · 2022Article
- Mice with gene alterations in the GH and IGF family.Pituitary · 2022Review
- Proteolysis in Reproduction: Lessons From Gene-Modified Organism Studies.Frontiers in endocrinology · 2022Review
- Transcription profile of the insulin-like growth factor signaling pathway during human ovarian follicular development.Journal of assisted reproduction and genetics · 2019Article
- ERK1/2-dependent gene expression in the bovine ovulating follicle.Scientific reports · 2018Article
- Insulin-Like Growth Factor Binding Proteins and IGFBP Proteases: A Dynamic System Regulating the Ovarian Folliculogenesis.Frontiers in endocrinology · 2018Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
The insulin-like growth factor (IGF) system plays an important role in regulating ovarian follicular development and steroidogenesis. IGF binding proteins (IGFBP) mostly inhibit IGF actions, and IGFBP proteolysis is a major mechanism for regulating IGF bioavailability. Pregnancy-associated plasma protein-A (PAPPA) is a secreted metalloprotease responsible for cleavage of IGFBP4 in the ovary. The aim of this study was to investigate whether PAPPA plays a role in regulating ovarian functions and female fertility by comparing the reproductive phenotype of wild-type (WT) mice with mice heterozygous or homozygous for a targeted Pappa gene deletion (heterozygous and PAPP-A knockout [KO] mice, respectively). When mated with WT males, PAPP-A KO females demonstrated an overall reduction in average litter size. PAPP-A KO mice had a reduced number of ovulated oocytes, lower serum estradiol levels following equine chorionic gonadotropin administration, lower serum progesterone levels after human chorionic gonadotropin injection, and reduced expression of ovarian steroidogenic enzyme genes, compared to WT controls. In PAPP-A KO mice, inhibitory IGFBP2, IGFBP3, and IGFBP4 ovarian gene expression was reduced postgonadotropin stimulation, suggesting some compensation within the ovarian IGF system. Expression levels of follicle-stimulating hormone receptor, luteinizing hormone receptor, and genes required for cumulus expansion were not affected. Analysis of preovulatory follicular fluid showed complete loss of IGFBP4 proteolytic activity in PAPP-A KO mice, demonstrating no compensation for loss of PAPPA proteolytic activity by other IGFBP proteases in vivo in the mouse ovary. Taken together, these data demonstrate an important role of PAPPA in modulating ovarian function and female fertility by control of the bioavailability of ovarian IGF.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.