Dysregulation of sphingolipid and cholesterol homeostasis imposes oxidative stress in human spermatozoa
Bibliographic record
Abstract
ABSTRACT Infertility is a significant public health concern, affecting one in six couples globally, with male-factor infertility representing half of all cases. Obesity is an important health problem and is increasingly linked to poor reproductive outcomes as it induces metabolic disturbances and dyslipidemia, both of which impair male fertility. Dyslipidemia, characterized by abnormal lipid profiles, is associated with declining sperm quality and alters cholesterol and sphingolipid abundances in the seminal plasma. Sperm capacitation enables spermatozoa to acquire fertilizing competence by promoting cholesterol efflux from the plasma membrane, modifying lipid composition and membrane fluidity, and enhancing the ability to recognize and fertilize the oocyte. However, the intricate interplay between cholesterol efflux and capacitation-associated modifications in human spermatozoa remains poorly understood. Sphingolipids, including Ceramide (Cer) and sphingosine-1-phosphate (S1P), are critical regulators of cellular functions that play a significant role in male reproductive health. These bioactive lipids and cholesterol promote sperm capacitation, motility, and the acrosome reaction (AR). We hypothesize that dysregulated lipid homeostasis, as seen in cases of dyslipidemia, can impair capacitation by disrupting lipid-signalling pathways and promoting oxidative stress. Our results demonstrate that methyl-β-cyclodextrin (MβCD), which extracts cholesterol from the sperm plasma membrane, enhances a variety of capacitation-associated adaptations, including tyrosine phosphorylation, hyperactive motility, and AR. Moreover, sphingolipid signalling, through the S1PR1/3 receptors, is crucial in mediating these effects. MβCD-cholesterol extraction is also associated with nitric oxide (NO) and superoxide (O 2 •- ) production, key signalling molecules involved in capacitation. However, dysregulated lipid metabolism, characterized by elevated cholesterol sulfate (Chol-SO 4 ), Cer, and Sphingosine (Sph), impairs sperm capacitation through excessive oxidative stress and promotes oxidative damage. The findings suggest that disruptions in lipid metabolism resulting from conditions like obesity can interfere with sperm capacitation and fertilizing potential, providing new insights into male infertility mechanisms.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".