Purpose: Undercarboxylated-OCN (ucOCN), acting on the receptor GPRC6A, was shown to stimulate of testosterone (T) production in Leydig cells in rodents, in parallel with the hypothalamus/pituitary/gonadal axis mediated by luteinizing hormone (LH). Hence, reduced serum ucOCN and/or inactivating gene variants of GPRC6A, are supposed to affect testis function in humans. The aim of this study is to evaluate the association among serum ucOCN, rs2247911 GPRC6A gene polymorphism and the endocrine/reproductive pattern in a cohort of Syrian infertile males, possibly confirming the role of ucOCN/GPRC6A axis on testis function.
Methods: A total of 172 males, including 62 oligozoospermic,51 azoosperminc patients and 59 age-matched normozoospermic controls, were prospectively recruited at the Orient Hospital for Assisted Reproduction Treatment (Syria) and evaluated for the hormonal pattern, serum OCN, glycemic and lipid profile. Screening for rs2247911 GPRC6A gene polymorphism was also performed.
Results: Serum ucOCN correlated positively with total sperm count, sperm morphology and motility, total T, E2 and HDL-cholesterol, and negatively with LH, FSH, and LDL-cholesterol. Patients bearing the GG genotype of rs2247911 polymophism had higher sperm count (P=0.008), progressive motility(P=0.05), normal morphology(P=0.009), T (P=0.003), HDL-cholesterol (P=0.008) and lower triglycerides levels (P<0.001) compared to patients bearing AG and AA genotypes. Aside of LH levels, rs2274911 gene polymorphism (P=0.024), and to a minor extent ucOCN, were major predictors of serum T at linear stepwise regression analysis.
Conclusions: The novel ucOCN/GPRC6A axis was confirmed to participate in the regulation of the endocrine and reproductive function of the testis through the production of T.
21 May 2022 - 24 May 2022