Obesity and cryptorchidism across development: an integrated endocrine and metabolic life course framework

Childhood obesity is a major endocrine and metabolic disorder that extends beyond cardiometabolic risk and may affect male reproductive development. Cryptorchidism (undescended testis, UDT) is a common congenital anomaly associated with hypogonadism, subfertility, and testicular cancer. However, endocrine and metabolic links between obesity and impaired testicular descent remain incompletely integrated.

This mini review synthesizes current evidence into an integrated life-course framework explaining how obesogenic exposures, including maternal metabolic disease, postnatal adiposity, and endocrine disrupting chemicals (EDCs), may interfere with testicular descent and gonadal maturation.

We integrate human and experimental evidence across prenatal life, minipuberty, childhood, and puberty, focusing on Leydig cell hormones (INSL3 and testosterone), hypothalamic-pituitary-gonadal (HPG) axis regulation, sex hormone binding globulin (SHBG), aromatase activity, leptin and insulin signaling, and EDC exposure.

Maternal obesity and gestational metabolic disorders may be associated with an inflammatory and hormonal milieu that could plausibly impair Leydig cell function and influence testicular development. Postnatal and adolescent obesity may shift sex steroid balance through increased aromatization, reduced SHBG, and altered central gonadotropin signaling, potentially influencing gonadal maturation and testicular position maintenance. EDCs with anti-androgenic and obesogenic properties may amplify these disturbances across development.

Integrating endocrine and metabolic mechanisms places cryptorchidism within a broader developmental and metabolic context rather than as an isolated anatomic anomaly.