Inter-organ communication is a cornerstone of endocrinology research, yet resolving these interactions at the cellular and molecular level remains challenging. Skeletal muscle constitutes approximately 40–50% of body mass and functions as a major endocrine organ, secreting bioactive molecules termed myokines that act on distant physiological systems. Despite growing interest in muscle–organ crosstalk, how myokines contribute to female reproductive function remains incompletely defined. Recent evidence demonstrates that the myokine myostatin regulates pituitary and associated ovarian function(1). Here, we investigated the relationship between skeletal muscle and female reproductive endocrinology using a novel secretory tagging approach in mice.
We developed an adeno-associated viral (AAV) vector-based tool that labels proteins as they transit the classical secretory pathway in skeletal muscle. Using the proximity-labelling TurboID methodology(2), we validated secretion of tagged proteins into culture media in vitro and into serum in female mice in vivo. Proteomic analysis of serum from mice identified over 160 classically secreted, muscle-derived proteins under basal conditions. Critically, tagged proteins were detected within reproductive tissues, including the ovary and uterus, as well as the pituitary gland, providing direct evidence that muscle-secreted factors reach these distal targets. We further characterised how the muscle secretome is remodelled during nutrient deficiency, a physiological state associated with reproductive dysfunction in female mice(3).
Together, this work establishes an unbiased, organ-resolved framework for studying the secretome in vivo. While our findings centre on muscle–reproductive crosstalk, this AAV-based approach is broadly adaptable for dissecting integrated physiology and endocrine signalling across other tissue axes.