Preserving Fertility: Minimizing Ovarian Lymphatic Drainage Disruption in Gynecological Cancer Surgeries

Abstract

Abstract Background In systematic lymphadenectomy surgeries for gynecological malignancies, the potential disruption of ovarian lymphatic drainage function is a concern, particularly in individuals with a vested interest in fertility preservation. However, the current impact of lymphatic drainage disruption on ovarian function remains unclear and has not received sufficient attention from clinical practitioners. This study aims to elucidate the effects of ovarian lymphatic drainage obstruction on ovarian function in mice. Methods Evans blue dye was injected into the ovaries of mice to visualize ovarian draining lymphatic vessels (dLVs), which were subsequently ligated under the stereomicroscope, aiming to replicate the surgical injury to the ovarian lymphatic drainage during systematic lymphadenectomy. Serum estradiol, progesterone and anti-Müllerian hormone (AMH) levels were detected by ELISA, the number of follicles was counted by H&E staining, pregnancy rate and average litter sizes were evaluated through mating test, and the oocyte quality was assessed via spindle staining, ROS level detection, and Annexin-V staining. Additionally, immune cells and cytokines in the ovary were analyzed. Results Following intraovarian injection of Evans blue dye, the lymphatic vessels near the porta ovarii were blue, subsequently draining into the draining lymphatic nodes (dLNs) in the dorsal region of the upper pole of the kidney. At 30 days post dLV ligation, the ligation group exhibited a significant increase in ovarian weight and ovarian index compared to the control group. Obstruction of ovarian lymphatic drainage led to the decrease of serum progesterone and AMH levels by nearly 50%, the decrease of growing follicles and the increase of atretic follicles. The pregnancy rate decreased from 81.9–29.8% and the average litter size decreased from 5.6 to 3.3 per female in the ligation group. Furthermore, obstruction of ovarian lymphatic drainage elevated oxidative stress levels in oocytes, promoted oocyte apoptosis and meiosis arrest. These outcomes of impaired ovarian function may be attributed to the disturbance of the ovarian immune microenvironment, characterized by an increase of macrophages and the proinflammatory factors IL-6 in mouse ovaries. Conclusions The obstruction of ovarian lymphatic drainage leads to ovarian dysfunction, suggesting the importance of minimizing disruption to the ovarian lymphatic drainage pathway during lymphadenectomy, particularly in cases involving fertility preservation management.