Stable Expression of Human Endogenous Retrovirus Families and Epigenetic Repressors in Human Granulosa Cells Across Oocyte Maturation Stages

ABSTRACT

Human endogenous retroviruses (HERVs) comprise a substantial portion of the human genome and are increasingly recognized as regulators of developmental and tissue‐specific transcription. While their expression has been widely studied in early embryos and pluripotent stem cells, little is known about their regulation within the ovarian follicular environment. This study aimed to characterize selected HERV families and their main epigenetic repressors in human granulosa cells associated with oocytes at different maturation stages. Expression of HERV‐H, HERV‐K, and HERV‐W families was analyzed, focusing on pol genes, the HERV‐W env gene, and the envelope‐derived proteins Syncytin‐1 and Syncytin‐2. The epigenetic repressors TRIM28 and SETDB1 were also evaluated. Samples were stratified into mature metaphase II (M2) and immature metaphase I–germinal vesicle (M1–GV) groups. All targets were consistently expressed. Quantitative analyses showed comparable transcriptional levels between M2‐ and M1–GV‐associated samples, with no significant differences. In an exploratory analysis restricted to M2 oocytes, lower HERV‐H expression was nominally associated with successful fertilization (unadjusted p  = 0.0292), requiring independent confirmation. HERV transcription and its silencing machinery are stably maintained in granulosa cells across oocyte maturation stages, suggesting a tightly regulated transcriptional equilibrium within the follicular microenvironment.