Secondary antibody therapy outperforms corticosteroids in an ameliorating lipopolysaccharide-induced rat model of premature ovarian failure

Premature ovarian failure (POF) is a significant cause of infertility and is often linked to autoimmune aetiologies. Lipopolysaccharide (LPS)-induced inflammation is a well-established model of autoimmune POF in rodents. Immunomodulatory treatments involving corticosteroids, frankincense, and targeted secondary antibodies have been hypothesised to mitigate the autoimmune response, reduce anti-ovarian antibody (AOA) levels, and restore ovarian function in an LPS-induced POF rat model. A POF model was established in female albino rats via the intraperitoneal injection of LPS. The rats were then divided into groups that received no treatment (LPS control), dexamethasone (DEX-treated LPS-treated rats), methylprednisolone (MP-treated LPS-treated rats), frankincense (Frankincense-treated LPS-treated rats), or secondary anti-ovarian antibodies (secondary Ab-treated LPS-treated rats) for 3 to 4 weeks. The serum levels of AOA, 17β-oestradiol, follicle-stimulating hormone (FSH), and luteinising hormone (LH) were assayed via commercial enzyme-linked immunosorbent assay (ELISA) kits. Ovarian tissues were examined histopathologically to assess structural damage and recovery. LPS induction successfully created a POF phenotype, as evidenced by significantly elevated AOA levels (P < 0.001), reduced 17β-oestradiol (P < 0.001), elevated FSH/LH (P < 0.001 and P < 0.05, respectively), and severe histopathological damage, including follicular atresia. All the treatments restored 17β-oestradiol levels. Secondary antibody therapy was most effective, normalising all hormonal parameters, significantly reducing AOA levels, and demonstrating complete histological recovery with healthy follicles and corpora lutea. MP potently suppressed AOA but paradoxically elevated FSH, without improving ovarian histology. DEX and frankincense showed intermediate efficacy, improving some hormonal and serological markers but failing to achieve full histological restoration. These findings demonstrate that targeted immunotherapy using secondary antibodies is superior to broad immunosuppression or anti-inflammatory treatment for restoring ovarian function in patients with autoimmune POF. While corticosteroids effectively reduce AOA titres, they may not reverse ovarian damage and can disrupt the hormonal balance. This underscores the need for precise, biomarker-guided therapies over nonspecific immunosuppression in patients with autoimmune ovarian insufficiency.