Ly49 knockdown in mice results in aberrant uterine crypt formation and impaired blastocyst implantation

•The role of the Ly49 family of receptors in implantation is investigated.•Knockdown of Ly49 in mice resulted in aberrant crypt formation.•Knockdown of Ly49 in mice affected blastocyst implantation.•Ly49 expressed by non-lymphoid leukocytes is important for implantation.

Genetic knockdown (KD) of the mouse Ly49 receptor family is reported to result in infertility despite the presence of zona-enclosed blastocysts in the uterus. Ly49 receptors regulate leukocyte functions particularly Natural Killer (NK) cell functions and are analogous to human killer immunoglobulin-like receptors (KIRs). Histological analyses of gd3.5–4.5 B6.Ly49KD uteri identified hatched but retarded blastocysts with pyknotic nuclei, aberrant endometrial crypt formation and impaired uterine lumen closure accompanied by a lack of primary decidualization These data support peri-implantation roles for leukocytes expressing the Ly49 receptor repertoire and may give insight into KIR-based regulation of human infertility.