Neonatal Maternal Separation Alters Gelatinase Activity in Mouse Ovarian Preantral Follicles

Objective: The early life environment is critical for normal growth and development for future reproductive function. This study aims to investigate the effect of neonatal maternal separation (MS) on gelatinase activity of mouse ovarian follicles. Materials and Methods: In this experimental study, infants from female NMRI mice were randomly allocated into two groups immediately after birth: i. MS isolated from their mothers for 6 hours per day, from postpartum days 2 to 16) and ii. Control (undisturbed during the 16 days). Ovarian tissues were dissected to perform differential counts of the ovarian follicle type by haematoxylin and eosin staining. The isolated follicles were cultured for 12 days. Gelatinase activity and the gene expressions of matrix metalloproteinases, MMP2 and MMP9, and their tissue inhibitors, TIMP1 and TIMP2, were evaluated by zymography and real-time polymerase chain reaction (PCR), respectively. Results: Follicle counts at the different developmental stages were significantly different between the control and MS groups. There was a significant decrease in gelatinase activity in the MS group compared to the control group. The MS group showed significantly decreased gene expression levels of MMP2 and MMP9 compared to the control group. In contrast, the gene expression levels of TIMP1 and TIMP2 significantly increased in the MS group compared to the control group. Conclusion: MS is a stressor agent that compromises ovarian follicle development, at least via disruption of gelatinase activity and its related gene expressions.