Molecular Impact of Social Isolation on Implantation Gene Expression in Uterine Tissue: A Rabbit Model for Stress-Induced Fertility Disorders

Introduction: Psychosocial stress, particularly social isolation, is increasingly recognized as a potential factor influencing female infertility by disrupting hormonal balance and impairing the implant ability of the endometrium. Women who undergo major life transitions such as migration, displacement, or adaptation to new sociocultural environments show greater vulnerability to chronic stress, which can negatively impact reproductive function and contribute to delayed conception. To investigate the effect of social isolation on reproductive hormones and implantation-related gene expression in female rabbits, serving as a model for human psychosocial stress.Materials and Methods: Eighty healthy female rabbits (۶–۸ months old) were randomly assigned into two groups: the control group (n = ۴۰), which received standard housing and care, and the stress group (n = ۴۰), which was in complete social isolation for ۱۴ days before and ۱۴ days after mating. On day ۷ post-mating, blood collection for hormone level measurement (FSH, LH, estrogen, progesterone, and cortisol) was done using standard protocols of the ELISA technique. On the same day, a hysterectomy was performed on these two groups, and uterine tissues were collected for analysis of gene expression by real-time PCR analysis of three implantation-related genes including LIF, HOXA۱۰, and Integrin β۳. Results: Social isolation significantly reduced FSH, LH, estrogen, and progesterone levels while increasing cortisol (p<۰.۰۵). Gene expression analysis revealed significant downregulation of LIF (p = ۰.۰۰۰۰۱۴), HOXA۱۰ (p = ۰.۰۱۴۵) and Integrin β۳ (p = ۰.۰۰۰۴) in the stress group compared to controls, indicating impaired uterine receptivity for implantation.Conclusions: It is concluded that chronic social isolation leads to hormonal imbalance and suppression of implantation-related gene expression, highlighting potential mechanisms for stress-related infertility and opening the door to clinical interventions targeting stress management to improve reproductive outcomes.

Keywords:

Social isolation , Psychosocial Stress , Fertility , Implantation Genes , Rabbits