Correlation between Serum Kisspeptin and Spermatogenic Function in Men

Abstract

Kisspeptin along with its receptor GPR54 or KISS1R regulates the secretion of hormones involved in the hypothalamic-pituitary-testicular axis, which is one of the contributing factors of adolescent spermatogenesis. This study aimed to investigate the correlation between serum kisspeptin concentration and spermatogenic function, and its predictive value in azoospermia. We retrospectively analyzed data of 196 males who visited the Reproductive Medicine Center of Qilu Hospital of Shandong University from June-November 2018; 20 were fertile and 176 were infertile. The following semen tests were performed: serum kisspeptin level by enzyme immunoassay; and levels of follicle-stimulating and luteinizing hormones, and testosterone by chemiluminescence assay. Percutaneous testicular sperm aspiration was performed on males with azoospermia. Subjects were divided into 5 groups: azoospermia (group A: 22 men with obstructive azoospermia; group B: 54 men with non-obstructive azoospermia), oligospermia (group C: 56 men), infertility with normal semen concentration (group D: 44 men), and fertility with normal semen concentration (group E: 20 men). Kisspeptin levels in the fertile group were higher than those in the infertile group. Levels of serum hormones, testosterone, and kisspeptin correlated with sperm concentration, with the strongest correlation between kisspeptin and sperm concentration (correlation coefficient=0.692). Levels of kisspeptin in obstructive and non-obstructive azoospermia groups were analyzed using Receiver-Operating-Curve analysis. A serum kisspeptin level ≥80.655 was classified as obstructive azoospermia; otherwise, the classification was nonobstructive azoospermia. Serum kisspeptin levels in the fertility group were significantly higher than that in the infertility group; this suggests kisspeptin may be associated with male fertility. Moreover, kisspeptin had a stronger correlation with sperm concentration than the hormones. A serum kisspeptin level of 80.655 can be used to differentiate obstructive and non-obstructive azoospermia.

Human-specific epigenomic states in spermatogenesis

“…Genetic variants leading to loss of kisspeptin/GPR54 signaling can lead to a hypogonadotropic hypogonadism phenotype in mice, with substantially smaller testes and ovaries than in wild type animals, arrested spermatogenesis mainly at early haploid spermatid stage, failure of folliculogenesis and ovulation, as well as impaired uterine endometrial gland development [50] , [51] . Similar phenotypes have been observed in human, where loss-of-function KISS1 variants led to normosmic idiopathic hypogonadotropic hypogonadism inherited in an autosomal recessive fashion [61] , and decreased circulating kisspeptin level has been associated with impaired spermatogenesis in human in a dose-dependent manner [62] . Intriguingly, kisspeptin has been implicated in regulation of puberty timing [47] , [60] , [63] ; increased kisspeptin/GPR54 signaling in the hypothalamus triggers puberty initiation in rodents and primates [47] , [60] .…”

Correlation of serum kisspeptin and leptin with non-obstructive azoospermia: A cross-sectional study in a subset of Karachi population

“…Other studies have also reported significantly decreased kisspeptin levels in infertile males and NOA. 10,22 This study has revealed the direct effect of kisspeptin on testicular function by affecting steroidogenesis and spermatogenesis. Hence levels of kisspeptin can be used to access spermatogenesis in NOA.…”