Seminal plasma metabolomics and lipidomics profiling to identify signatures of pituitary stalk interruption syndrome

Abstract

Background Pituitary stalk interruption syndrome (PSIS) is a rare disease caused by congenital pituitary anatomical defects. The underlying mechanisms remain unclear, and the diagnosis is difficult. Here, integrated metabolomics and lipidomics profiling were conducted to study the pathogenesis of PSIS. Methods Twenty-one patients with PSIS (BD group) and twenty-three healthy controls (HC group) were enrolled. Basal information and seminal plasma samples were collected. Untargeted metabolomics and lipidomics analyses were performed using ultraperformance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS). Results The metabolomics and lipidomics profiles of patients with PSIS changed. The prolactin signaling pathway and biosynthesis of amino acids were the main differentially modified metabolic pathways. The main differentially modified metabolites were triacylglycerols (TGs), phosphatidylethanolamine (PE), sphingomyelin (SM), ceramide (Cer) and phosphatidylcholines (PCs). Pregnenolones and L-saccharopine could achieve a diagnosis of PSIS. Conclusions Pregnenolones and L-saccharopine are potential biomarkers for a PSIS diagnosis.

Lipidomics random forest algorithm of seminal plasma is a promising method for enhancing the diagnosis of necrozoospermia

“…Yolk freezing protection solutions containing PE can reduce damage to spermatozoa membranes and vitality caused by freezing (Pillet et al, 2012 ). Lipidomic studies of seminal plasma in patients with pituitary stalk interruption syndrome observed a downregulation of PE, consistent with our research findings (Guo et al, 2022 ). Li et al demonstrated that PE and TG serve as biomarkers for diagnosing Kallmann syndrome (Li et al, 2021 ).…”

“…SM(d36:2) and SM(d18:1_18:1) are differentially expressed lipids, with their downregulation indicating a correlation between the occurrence of necrozoospermia and decreased levels of SM in seminal plasma. In patients with pituitary stalk interruption syndrome, seminal plasma lipids such as SM(d38:2), SM(d40:2), SM(d36:1), SM(d34:1), SM(d42:1), and SM(d42:3) were also downregulated, aligning with our findings and suggesting abnormal nutritional conditions in the spermatozoa survival microenvironment (Guo et al, 2022 ).…”

Pulsatile gonadotropin-releasing hormone therapy induces spermatogenesis in pituitary stalk interruption syndrome: A case report and review of the literature

“…Enhanced MRI diagnostics using gadopentetate dimeglumine (Gd-DTPA) have proven to be more sensitive in identifying the vascular components of the pituitary stalk, offering new insights into the partial preservation of hypothalamo-hypophyseal portal circulation[ 30 ]. Guo et al [ 31 ] conducted a study comparing the metabolomics and lipidomics of seminal plasma in 21 PSIS patients and 23 healthy controls, identifying altered metabolites such as triacylglycerols, phosphatidylethanolamines, sphingomyelins, ceramides, and phosphatidylcholines in PSIS patients. Through bioinformatics assessments and receiver operating characteristic curve modeling, they identified pregnenolone and L-saccharopine as potential biomarkers for PSIS, emphasizing the need for further validation in future research.…”