Comparative analysis of ERK and CREB activity in normal and cryptorchid testes of bulls

Abstract

Importance: Cryptorchidism, defined as the failure of one or both testes to descend into the scrotum, is a pathological condition that adversely impacts testicular development and spermatogenic function. In livestock, particularly bulls, such impairment can lead to substantial economic losses due to compromised fertility. A comprehensive understanding of the morphological and molecular alterations associated with cryptorchidism is essential for efforts to develop effective diagnostic and therapeutic strategies. Objective: This study aimed to examine morphological changes and changes in the extracellular signal-regulated kinase (ERK) and cyclic AMP response element-binding protein (CREB) activity in the testes of bulls with cryptorchidism. Methods: Testes from the 18-month-old unilateral cryptorchid bulls, including the descended (normal) and undescended (cryptorchid) testes from each animal, were analyzed through gross examination, histology, immunohistochemistry (Ki-67, phosphorylated p-ERK, p-CREB), and Western blotting. Results: Cryptorchid testes were smaller and exhibited reduced epithelial thickness, although seminiferous tubule area remained unchanged. Expression of Ki-67, p-ERK, and p-CREB was significantly decreased, indicating impaired cell proliferation and signaling. Total ERK and CREB protein levels were unchanged, but phosphorylation levels were notably reduced in cryptorchid samples. Conclusions and Relevance: Our findings demonstrate that cryptorchidism alters testicular morphology and disrupts key signaling pathways, particularly those involved in cell growth and function. Such alterations may contribute to infertility and highlight the importance of early diagnosis and intervention in the context of reproductive management in livestock.