Activin A is a functional component of the anti-endometriotic drug Endoferin

Endometriosis is a prevalent gynecological condition affecting up to 25-40% of women with infertility. Endoferin, a protein complex derived from the bovine ovarian follicles, has demonstrated high efficacy in clinical trials for treating endometriosis. It contains bovine serum albumin and a biologically active protein from the TGF-β superfamily. However, the mechanisms underlying its therapeutic effects are not studied well. Heating Endoferin facilitated the processing of pro-activin A to activin A, resulting in the active drug Endoferin and enhancing its differentiation-inducing activity in Xenopus ectoderm. Inhibitory analysis showed that targeted proteolysis activates Endoferin. Protease -mediated processing of pro-activin A is crucial for activating activin A within the preparation. The morphometric analysis of the endometriomas showed a significant size reduction in rats treated with Endoferin (Cohen's d = 1.5). Immunohistochemical analysis showed that Endoferin treatment significantly decreased VEGF expression (Cohen's d = 1.5) compared to control, as well as reducing the levels of Ki-67 expression (Cohen's d = 1.25), and increased apoptosis indices (Cohen's d = 0,87) in rat endometriotic tissue samples. The therapeutic efficacy of Endoferin in the treatment of endometriosis is explained by the ability of activin A to suppress angiogenesis and induce apoptosis in endometrioid lesions. In addition, Endoferin is isolated from follicular fluid, contains other biologically active substances, and exhibits pronounced antiproliferative activity that cannot be explained solely by the effects of activin A. These findings support the use of Endoferin as a promising treatment option for endometriosis without steroid hormones or their analogues.