Tachykinin-directed gonadotropin-independent follicular growth: Evolutionary conservation and divergence between mouse and Ciona robusta.

Follicular development proceeds through gonadotropin-independent and gonadotropin-dependent phases in vertebrates, yet the molecular mechanisms underlying the gonadotropin-independent stage remain poorly understood. Recent studies have revealed that tachykinins (TKs), a conserved family of neuropeptides, directly regulate early-stage (gonadotropin-independent) follicular growth in both the ascidian Ciona robusta and mouse Mus musculus. In ascidians, Ciona TK, CiTK, specifically promotes vitellogenic follicle growth via its receptor (CiTKR) expressed in test cells, upregulating cathepsin D and other proteases. In mice, three TKs (Substance P (SP); Neurokinin A (NKA); and Neurokinin B (NKB)) and their receptors are co-expressed in granulosa cells of secondary follicles, where these TKs act in autocrine/paracrine manners to induce follicle development and oocyte growth. This process involves direct activation of cathepsin D and the JAK1-STAT3-COX-2-prostaglandin pathway. These studies verify that the TK-cathepsin D pathway is an evolutionarily conserved gonadotropin-independent system across Olfactores (ascidians and vertebrates), since the hypothalamus-pituitary-gonadal (HPG) axis is restricted to vertebrates. Notably, the TK-mediated pathway is active prior to sexual maturity in mice, suggesting that normal early-stage follicle development is essential for reproductive capacity and offspring viability. Collectively, investigation of TK-driven gonadotropin-independent folliculogenesis provides new insights into reproductive and evolutionary biology.