ArticleReproductive biology and endocrinology : RB&E2022
Delayed puberty, gonadotropin abnormalities and subfertility in male Padi2/Padi4 double knockout mice.
Article in Reproductive biology and endocrinology : RB&E, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 8 citations in OpenAlex.
- Ezrin, radixin, and moesin are novel citrullinated proteins in the decidua during pregnancy†.Biology of reproduction · 2026Article
- Cardiac PAD2 expression and myocardial citrullination decline with age in female mice independent of estrogen.American journal of physiology. Heart and circulatory physiology · 2025Article
- A coming-of-age story: adult neurogenesis or adolescent neurogenesis in rodents?Frontiers in neuroscience · 2024Article
- Co-expression of PADI isoforms during progenitor differentiation enables functional diversity.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023Article
- Protein citrullination: inhibition, identification and insertion.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023Review
- Current insights into the role of citrullination in thrombosis.Current opinion in chemical biology · 2023Review
- Peptidylarginine deiminase 2 citrullinates MZB1 and promotes the secretion of IgM and IgA.Frontiers in immunology · 2023Article
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundPeptidylarginine deiminase enzymes (PADs) convert arginine residues to citrulline in a process called citrullination or deimination. Recently, two PADs, PAD2 and PAD4, have been linked to hormone signaling in vitro and the goal of this study was to test for links between PAD2/PAD4 and hormone signaling in vivo.
methodsPreliminary analysis of Padi2 and Padi4 single knockout (SKO) mice did not find any overt reproductive defects and we predicted that this was likely due to genetic compensation. To test this hypothesis, we created a Padi2/Padi4 double knockout (DKO) mouse model and tested these mice along with wild-type FVB/NJ (WT) and both strains of SKO mice for a range of reproductive defects.
resultsControlled breeding trials found that male DKO mice appeared to take longer to have their first litter than WT controls. This tendency was maintained when these mice were mated to either DKO or WT females. Additionally, unsexed 2-day old DKO pups and male DKO weanlings both weighed significantly less than their WT counterparts, took significantly longer than WT males to reach puberty, and had consistently lower serum testosterone levels. Furthermore, 90-day old adult DKO males had smaller testes than WT males with increased rates of germ cell apoptosis.
conclusionsThe Padi2/Padi4 DKO mouse model provides a new tool for investigating PAD function and outcomes from our studies provide the first in vivo evidence linking PADs with hormone signaling.
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