Semaphorin 3A (
SEMA3A) plays a crucial role in the development, differentiation, and plasticity of specific types of neurons that secrete
Gonadotropin-Releasing Hormone (
GnRH) and regulates the acquisition and maintenance of reproductive competence in humans and mice. Its insufficient expression has been linked to reproductive disorders in humans, which are characterized by reduced or failed sexual competence. Various mutations, polymorphisms, and alternatively spliced variants of
SEMA3A have been associated with
infertility. One of the common causes of
infertility in women of reproductive age is diminished ovarian reserve (DOR), characterized by a reduced ovarian follicular pool. Despite its clinical significance, there are no universally accepted diagnostic criteria or therapeutic interventions for DOR. In this study, we analyzed the
SEMA3A plasma levels in 77 women and investigated their potential role in influencing fertility in patients with DOR. The results revealed that the
SEMA3A levels were significantly higher in patients with DOR than in healthy volunteers. Furthermore, the
SEMA3A levels were increased in patients who underwent fertility treatment and had positive Beta-
Human Chorionic Gonadotropin (βHCG) values (β+) after controlled ovarian stimulation (COS) compared to those who had negative βHCG values (β-). These findings may serve as the basis for future investigations into the diagnosis of
infertility and emphasize new possibilities for the SEMA3A-related treatment of sexual hormonal dysfunction that leads to
infertility.