Delayed puberty, gonadotropin abnormalities and subfertility in male Padi2/Padi4 double knockout mice
Abstract Background Peptidylarginine 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/PAD...
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| Format: | Article |
| Language: | English |
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BMC
2022-10-01
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| Series: | Reproductive Biology and Endocrinology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12958-022-01018-w |
| _version_ | 1798029906391597056 |
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| author | Kelly L. Sams Chinatsu Mukai Brooke A. Marks Chitvan Mittal Elena Alina Demeter Sophie Nelissen Jennifer K. Grenier Ann E. Tate Faraz Ahmed Scott A. Coonrod |
| author_facet | Kelly L. Sams Chinatsu Mukai Brooke A. Marks Chitvan Mittal Elena Alina Demeter Sophie Nelissen Jennifer K. Grenier Ann E. Tate Faraz Ahmed Scott A. Coonrod |
| author_sort | Kelly L. Sams |
| collection | DOAJ |
| description | Abstract Background Peptidylarginine 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. Methods Preliminary 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. Results Controlled 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. Conclusions The 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. |
| first_indexed | 2024-04-11T19:32:39Z |
| format | Article |
| id | doaj.art-2bdd95194a7f4186a8fd4b000a5e765e |
| institution | Directory Open Access Journal |
| issn | 1477-7827 |
| language | English |
| last_indexed | 2024-04-11T19:32:39Z |
| publishDate | 2022-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Reproductive Biology and Endocrinology |
| spelling | doaj.art-2bdd95194a7f4186a8fd4b000a5e765e2022-12-22T04:06:57ZengBMCReproductive Biology and Endocrinology1477-78272022-10-0120111410.1186/s12958-022-01018-wDelayed puberty, gonadotropin abnormalities and subfertility in male Padi2/Padi4 double knockout miceKelly L. Sams0Chinatsu Mukai1Brooke A. Marks2Chitvan Mittal3Elena Alina Demeter4Sophie Nelissen5Jennifer K. Grenier6Ann E. Tate7Faraz Ahmed8Scott A. Coonrod9Baker Institute for Animal Health, College of Veterinary Medicine, Cornell UniversityBaker Institute for Animal Health, College of Veterinary Medicine, Cornell UniversityBaker Institute for Animal Health, College of Veterinary Medicine, Cornell UniversityBaker Institute for Animal Health, College of Veterinary Medicine, Cornell UniversityDepartment of Biomedical Sciences, College of Veterinary Medicine, Cornell UniversityDepartment of Biomedical Sciences, College of Veterinary Medicine, Cornell UniversityTranscriptional Regulation and Expression Facility, Department of Biomedical Sciences, Cornell UniversityTranscriptional Regulation and Expression Facility, Department of Biomedical Sciences, Cornell UniversityTranscriptional Regulation and Expression Facility, Department of Biomedical Sciences, Cornell UniversityBaker Institute for Animal Health, College of Veterinary Medicine, Cornell UniversityAbstract Background Peptidylarginine 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. Methods Preliminary 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. Results Controlled 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. Conclusions The 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.https://doi.org/10.1186/s12958-022-01018-wPAD2PAD4CitrullinationHormone signalingEstrogen receptorAndrogen receptor |
| spellingShingle | Kelly L. Sams Chinatsu Mukai Brooke A. Marks Chitvan Mittal Elena Alina Demeter Sophie Nelissen Jennifer K. Grenier Ann E. Tate Faraz Ahmed Scott A. Coonrod Delayed puberty, gonadotropin abnormalities and subfertility in male Padi2/Padi4 double knockout mice Reproductive Biology and Endocrinology PAD2 PAD4 Citrullination Hormone signaling Estrogen receptor Androgen receptor |
| title | Delayed puberty, gonadotropin abnormalities and subfertility in male Padi2/Padi4 double knockout mice |
| title_full | Delayed puberty, gonadotropin abnormalities and subfertility in male Padi2/Padi4 double knockout mice |
| title_fullStr | Delayed puberty, gonadotropin abnormalities and subfertility in male Padi2/Padi4 double knockout mice |
| title_full_unstemmed | Delayed puberty, gonadotropin abnormalities and subfertility in male Padi2/Padi4 double knockout mice |
| title_short | Delayed puberty, gonadotropin abnormalities and subfertility in male Padi2/Padi4 double knockout mice |
| title_sort | delayed puberty gonadotropin abnormalities and subfertility in male padi2 padi4 double knockout mice |
| topic | PAD2 PAD4 Citrullination Hormone signaling Estrogen receptor Androgen receptor |
| url | https://doi.org/10.1186/s12958-022-01018-w |
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