Lightning Talk + Poster ESA-SRB-NZSE-CaSR 2026 in conjunction with ENSA

Paternal beta-defensin 22 promotes uterine receptivity through modulating the endometrial transcriptome at pre-implantation in mice (144434)

Hon (Dexter) Y Chan 1 , Ricky A Matias 1 , Ha M Tran 1 , John E Schjenken 1 2 3 , Peck Y Chin 1 , David J Sharkey 1 , Lachlan M Moldenhauer 1 , Sarah A Robertson 1
  1. Robinson Research Institute & School of Pharmacy and Biomedical Science, College of Health, Adelaide University, Adelaide, SA 5005, Australia
  2. Centre for Reproductive Science, School of Science, College of Engineering, Science and Environment, University of Newcastle, NSW 2308, Australia
  3. Reproductive and Family Health Research Program, Hunter Medical Research Institute, NSW 2305, Australia

1.Background

In mammalian species, components of seminal plasma and sperm interact with the female reproductive tract after insemination to elicit an immune response that promotes reproductive success. Beta-defensins are antimicrobial and immune-modulatory peptides carried by sperm, with potential to interact with female reproductive tract tissues after mating. In men, the major seminal beta-defensin is DEFB126, and reduced DEFB126 is associated with impaired fertility.

 

2.Methods

CRISPR technology was utilised to generate C57Bl/6 mice with null mutation in Defb22, the murine ortholog of DEFB126 (Defb22-/-), and effects on female tract responses and mating outcomes were examined in wildtype Balb/c females.

 

3.Results

Mating with Defb22-/- males yielded pregnancies with 22% reduction in implantation rate (P<0.05), and 5% reduction in fetal weight in late gestation compared to control Defb22+/+ matings (n=24-30 dams/group, P<0.05). This was not attributable to fertilisation defects as blastocyst numbers and development at pre-implantation on day 3.5 post-coitum (d3.5pc) were not different in Defb22-/- matings compared to control (n=10-12). RNAseq analysis of the d3.5pc uterine endometrium (n=4/group) revealed 369 differentially regulated genes (48 upregulated and 321 downregulated) following mating with Defb22-/- males (FDR<0.1), with enrichment in implantation- and immune-associated pathways consistent with downregulation of receptivity-related genes Atp6v0d2, Wnt7b, Lifr, Bmp2, Igfbp3, Cebpb, Olfm1, Mmp7, and immune response genes Cd55, Csf1, Ptgs2. Upstream Regulator Analysis in Ingenuity Pathway Analysis identified signalling molecules known to be activated after natural mating, including pro-angiogenic factor VEGFA, decidualisation factors BMP2 and CEBPB, and cytokines IL6 and TNF, as predicted to be inhibited in the endometrium following Defb22-/- mating.

 

4.Conclusion

These data demonstrate that DEFB22 is required for optimal fertility in male mice and implicate a mechanism involving a role for seminal fluid DEFB22 in inducing female endometrial receptivity to support robust embryo implantation and fetal development.