Newly Identified Ovulation Regulator Shows Potential for Infertility Treatments

Researchers at Cornell University have uncovered a novel cell signaling pathway involved in the ovulation process, opening up new possibilities for addressing infertility, contraception, and ovarian health. The discovery centers around Semaphorin 3E (Sema3E), a protein traditionally known for its role in vascular, nervous, and immune system functions, as well as cancer development. In their study, published in Advanced Science and led by postdoctoral researcher Hanxue Zhang, the team demonstrated that Sema3E plays a crucial role in facilitating ovulation in mice.

Female reproductive tissues, such as the ovary, are unique in undergoing cyclical construction and deconstruction, regulated tightly by reproductive hormones. During ovulation, eggs are released from mature ovarian follicles. Interestingly, the interior of these follicles lacks direct blood supply before ovulation, but the process of egg release involves significant vascular remodeling, with blood vessels rapidly forming afterward—a phase comparable to aggressive tumor vascularization.

The research revealed that manipulating Sema3E disrupted ovulation and impaired the development of new blood vessels in the ovary, which are essential for supporting pregnancy. These findings suggest that targeting the Sema3E pathway could enhance reproductive performance and provide new avenues for contraceptive development or infertility treatments.

Furthermore, because reproductive hormones influence multiple body systems, understanding ovarian signaling pathways like Sema3E might also shed light on broader health issues, such as cardiovascular health and tumor growth. As Ren, a lead researcher, noted, "There's a whole world of possibilities to explore with this discovery." This fundamental research could eventually impact human reproductive health, veterinary practices, and a variety of biological processes influenced by hormones.

For more details, see the full study: Hanxue Zhang et al., "Semaphorin 3E–Plexin-D1 Pathway Downstream of the Luteinizing Hormone Surge Regulates Ovulation, Granulosa Cell Luteinization, and Ovarian Angiogenesis in Mice," Advanced Science (2025).