Dataset Information

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.

SUBMITTER: Guo Y

PROVIDER: S-EPMC9287950 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature

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Publications

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

Guo Ye Y Li Xiaogang X Wang Xi X Li Haolong H Luo Guoju G Si Yongzhen Y Wu Xueyan X Li Yongzhe Y

Orphanet journal of rare diseases 20220715 1

<h4>Background</h4>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.<h4>Methods</h4>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 ...[more]

PMID: 35841106

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Project description:Abstract Background Pituitary stalk interruption syndrome (PSIS) may associate with brain midline defects and also with polydactyly (GLI2 mutations) but rarely with brain cortex anomalies. Clinical Case We report a boy referred at age 19 months because of growth failure. Bilateral postaxial polydactyly, syndactyly of the toes, and a nodule on the tongue were noted at term birth. The neonatal course was complicated by marked but transient hypoglycemia. During infancy, the acquisition of gross motor skills was slightly delayed. Upon referral, body length was 4.1 SD below the level of mid-parental height. Extremely low concentrations of circulating IGF-I (8 mcg/L) and IGFBP-3 (861 mcg/L) were suggestive of growth hormone (GH) deficiency which was corroborated by glucagon test (peak GH 3.3 mcg/L, peak cortisol 14.6 mcg/dL) in an euthyroid and normoprolactinemic state, and in the absence of polydipsia or polyuria. Brain MRI disclosed not only a PSIS triad (with a virtual absence of the pituitary stalk and the anterior pituitary, and with an ectopic position of the posterior pituitary) but also abnormal sulcation and polymicrogyria (pointing to abnormal lamination in the cortex) on both sides in the posterior cingulum. Familial history is positive for holoprosencephaly and polydactyly in two male relatives, who died neonatally. Whole exome sequencing showed a rare maternally inherited variant in ZRSR2 on the X chromosome (c. 1207_1208delAG (p.Arg403Glyfs*24)) (OMIM 300028). ZRSR2 isdepleted from loss-of-function variants in the reference population, and has not been associated with congenital anomalies or with pituitary dysfunction. This ZRSR2 variant escapes nonsense mediated decay and segregates in this family according to an X-linked recessive pattern. X-inactivation studies and gene expression studies are ongoing to correlate the ZRSR2 variant to the patient's phenotype. Conclusion This case describes a toddler with polydactyly and short stature, based on GH deficiency due to PSIS, in combination with polymicrogyria. Studies are ongoing to link the patient's phenotype to a rare variant in ZRSR2. Presentation: Saturday, June 11, 2022 1:30 p.m. - 1:35 p.m., Saturday, June 11, 2022 1:30 p.m. - 1:35 p.m., Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

Project description:If strategies currently in development succeed in eradicating HIV reservoirs in peripheral blood and lymphoid tissues, residual sources of virus may remain in anatomic compartments. Paired blood and semen samples were collected from 12 individuals enrolled in a randomized, double-blind, placebo-controlled therapeutic vaccine clinical trial in people with HIV (PWH) who began antiretroviral therapy (ART) during acute or early infection (ClinicalTrials registration no. NCT01859325). After the week 56 visit (postintervention), all participants interrupted ART. At the first available time points after viral rebound, we sequenced HIV-1 env (C2-V3), gag (p24), and pol (reverse transcriptase) regions amplified from cell-free HIV RNA in blood and seminal plasma using the MiSeq Illumina platform. Comprehensive sequence and phylogenetic analyses were performed to evaluate viral population structure, compartmentalization, and viral diversity in blood and seminal plasma. Compared to that in blood, HIV RNA rebound in semen occurred significantly later (median of 66 versus 42 days post-ART interruption, P < 0.01) and reached lower levels (median 164 versus 16,090 copies/ml, P < 0.01). Three of five participants with available sequencing data presented compartmentalized viral rebound between blood and semen in one HIV coding region. Despite early ART initiation, HIV RNA molecular diversity was higher in semen than in blood in all three coding regions for most participants. Higher HIV RNA molecular diversity in the genital tract (compared to that in blood plasma) and evidence of compartmentalization illustrate the distinct evolutionary dynamics between these two compartments after ART interruption. Future research should evaluate whether the genital compartment might contribute to viral rebound in some PWH interrupting ART.IMPORTANCE To cure HIV, we likely need to target the reservoirs in all anatomic compartments. Here, we used sophisticated statistical and phylogenetic methods to analyze blood and semen samples collected from 12 persons with HIV who began antiretroviral therapy (ART) during very early HIV infection and who interrupted their ART as part of a clinical trial. First, we found that HIV RNA rebound in semen occurred significantly later and reached lower levels than in blood. Second, we found that the virus in semen was genetically different in some participants compared to that in blood. Finally, we found increased HIV RNA molecular diversity in semen compared to that in blood in almost all study participants. These data suggest that the HIV RNA populations emerging from the genital compartment after ART interruption might not be the same as those emerging from blood plasma. Future research should evaluate whether the genital compartment might contribute to viral rebound in some people with HIV (PWH) interrupting ART.

Dataset Information

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

Background

Methods

Results

Conclusions

Publications

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

Similar Datasets

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