Semaphorin 3A Increases in the Plasma of Women with Diminished Ovarian Reserve Who Respond Better to Controlled Ovarian Stimulation

Abstract

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.

Keywords: Gonadotropin-Releasing Hormone (GnRH); diminished ovarian reserve (DOR); in vitro fertilization (IVF); infertility; semaphorin 3A (SEMA3A).

Figure 1

SEMA3A increases in patients with DOR. SEMA3A levels in HLT and patients with DOR. Significance was calculated using unpaired t-test and expressed as a p value < 0.05. Data below the sensitivity of the kit were excluded.

Figure 2

SEMA3A increases in patients with DOR who responded better to ovarian stimulation. (A) SEMA3A levels in patients with DOR who were responsive or unresponsive to fertilization procedures. βneg: negative-βhCG; βpos: positive-βhCG; CC: cancelled cycle. Significance was calculated using ordinary one-way ANOVA followed by Tukey’s multiple comparisons test and expressed as p value < 0.05. Data below the sensitivity of the ELISA kit were excluded from the analysis. Spearman’s correlation analysis between SEMA3A and E2 (B), the number of follicles before trigger (C), and mature oocytes (MII oocytes) (D) after hormonal stimulation in women with DOR. R = Spearman’s correlation coefficient; the confidence interval (CI) was set at 95%; p values are reported in the graph. * p < 0.05; ** p < 0.01; *** p < 0.001.