Abnormal Sperm Morphology in Lodpr/lncRNA-HSVIII Knockout Mice with Advancing Age

A mouse testis-specific long noncoding RNA, Lodpr/lncRNA-HSVIII, is expressed in germ cells and Leydig cells; however, its functional role remains uncharacterized. To clarify the physiological role, we generated Lodpr/lncRNA-HSVIII knockout (KO) mice using the CRISPR/Cas9 technology. Although Lodpr/lncRNA-HSVIII KO mice did not exhibit infertility, their phenotypic traits were documented at 2 months and 6 months of age. Histological examination of testes revealed alterations in the stages of seminiferous tubules and an increased vascularization within the interstitial tissue in Lodpr/lncRNA-HSVIII KO specimens at both 2 months and 6 months. Notably, certain phenotypes emerged exclusively at 6 months. In the testes of 6-month-old KO mice, an increase in the number of Sertoli cells was noted within the seminiferous tubules, and clusters of germ cell degeneration, potentially resulting in vacuolation, were observed along with enlarged round spermatids. Additionally, in the mediastinum testis of some KO mice, an elongation of the transition zone and fibroblast proliferation within the interstitial tissue were evident at 6 months. In the cauda epididymis, there was a notable increase in extravascular leukocytes at 6 months. Sperm analysis indicated a significant elevation of abnormal sperm, especially bent tails, only in 6-month-old KO mice, despite no significant differences in overall sperm quantity and motility. Collectively, these findings suggest that Lodpr/lncRNA-HSVIII plays a role in modulating the morphology of sperm, testicular tissue, and the epididymis, with effects becoming more pronounced with age.