Delayed puberty, gonadotropin abnormalities and subfertility in male Padi2/Padi4 double knockout mice

• DOI: 10.1186/s12958-022-01018-w
• Publication Date: 2022-10-12T05:07:47Z
• Authors: 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
• Keywords: Knockout mouse; Gonadotropin

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 hormone signaling vitro the goal of this study was test for links between PAD2/PAD4 vivo.Preliminary analysis Padi2 Padi4 single knockout (SKO) mice did not find any overt reproductive defects we predicted that likely due genetic compensation. To hypothesis, created Padi2/Padi4 double (DKO) mouse model tested these along with wild-type FVB/NJ (WT) both strains SKO range defects.Controlled breeding trials found male DKO appeared take longer their first litter than WT controls. This tendency maintained when were mated either females. Additionally, unsexed 2-day old pups weanlings weighed significantly less counterparts, took males reach puberty, had consistently lower serum testosterone levels. Furthermore, 90-day adult smaller testes increased rates germ cell apoptosis.The provides new tool investigating PAD function outcomes from our studies provide vivo evidence linking PADs signaling.