F&S science最新文献

Objective: To investigate the metabolic alterations at the maternal-fetal interface in missed miscarriage (MM) using untargeted metabolomic and lipidomic profiling of paired villous and decidual tissues.

Design: Observational study utilizing multi-omics integration to analyze metabolic and lipidomic profiles.

Subjects: A total of 10 women were recruited in this study, including 5 women with MM and 5 healthy controls. All cases included in the MM group were euploid, excluding chromosomal abnormalities.

Exposure: The exposure in this study was the condition of MM, with tissue samples collected from both villous and decidual tissues.

Main outcome measures: Differentially abundant metabolites and lipids between MM and control groups, focusing on metabolic pathways related to glycerophospholipid metabolism, sphingolipid signaling, and amino acid metabolism.

Results: We identified significant metabolic alterations in both villous and decidual tissues from MM pregnancies compared to healthy controls. Key findings included the downregulation of amino acids and organic acids, such as lactic acid, suggesting impaired energy metabolism. Lipidomic analysis revealed alterations in glycerophospholipids and sphingolipids, indicating disrupted cell signaling and inflammatory pathways in MM.

Conclusion: This multi-omics study highlights specific metabolic and lipidomic disruptions in missed miscarriage, suggesting early metabolic disturbances at the maternal-fetal interface correlate with miscarriage. These findings may guide future therapeutic strategies targeting metabolic pathways to improve pregnancy outcomes in MM.

Objective: To investigate the therapeutic potential of ANA-12 in restoring testicular health by modulating local neurochemical balance in adult rats of passive smoking, secondhand smoking or environmental tobacco smoke/nicotine exposure.

Design: Preclinical rodent models mimicking a real-life human smoking scenario.

Groups: Post-acclimatization, adult male rats of 250-300 g body weight were randomized into passive smoking, oral nicotine, ANA-12 pre-treatment, and healthy unexposed controls.

Exposure: Rats were exposed to passive smoking through a whole-body inhalation chamber and oral nicotine through gavage with/without intraperitoneal administration of ANA-12 at differential dosages prior to passive smoking/nicotine exposure for a period of 4- and 12-week studies.

Main outcome measure(s): Testes histopathology, DNA damage potency, and fertility indices alongside redox homeostasis and expressions of local neurotransmitter dopamine and its receptors D1 and D2, and neurotrophic factor, brain-derived neurotrophic factor (BDNF) and its receptor, tyrosine kinase beta (Trk-β) in testes, comet assay in whole blood, and serum cotinine levels.

Result(s): Compared with the healthy unexposed controls, passive smoking and oral nicotine exposure dose- and time-dependently disrupt developing spermatogonia, spermatocytes, and spermatids of the seminiferous tubules and basement membrane; reduce sperm count with concomitant higher deoxyribonucleic acid (DNA) damage; and upregulate BDNF/Trk-β and dopamine/D1 expressions, as well as oxidative stress with subsequent antioxidant depletion in testes. In contrast, regardless of the duration of exposure, ANA-12 pre-treatment significantly restores germ cells of the seminiferous epithelium, improves spermatogenesis, downregulates aberrant local neurochemical systems, and maintains redox homeostasis in the testicular milieu. These results are in accordance with the whole blood DNA damage and serum cotinine levels, a biomarker of nicotine exposure.

Conclusion(s): The results offer a novel insight into therapeutic interventions for passive or secondhand smoking- or environmental tobacco smoke-induced male reproductive impairment via regulation of BDNF-dopaminergic signaling and antioxidant balance in testes by ANA-12, leading to improved fertility potential and overall testicular health, which could establish the modulation of the brain-testes axis, implicated in nicotine addiction. This study holds translational potential of ANA-12 for the management of smoking- or nicotine-related male infertility of individuals unable or unwilling to quit smoking.

Objective: To investigate the potential role of butyrylcholinesterase enzyme activity and tentative association of BChE gene SNPs polymorphisms (rs3495, rs1803274) with risk of male infertility. Male infertility is a highly prevalent multifactorial condition with complex heterogeneous phenotypic spectrum. A significant global variation has been observed in the prevalence of male infertility contributing to approximately 20-70% of overall infertility. An interplay of genetic, hormonal, environmental and lifestyle factors are involved in the development of male infertility. Butyrylcholinesterase (BChE), an enzyme involved in oxidative stress and sperm function may play a role in infertility, but its genetic and enzymatic profiles in male infertility are unexplored.

Study design: A case control/observational study was conducted enrolling fifty-five fertile and infertile male individuals.

Subjects: Sixty-five fertile and infertile males volunteers were included in the study EXPOSURE: Volunteers were clinically diagnosed for infertility.

Main outcome measures: Plasma BChE activity was estimated spectrophotometrically by Ellman's method. SNP genotyping of BChE gene variants was performed by PCR-RFLP (polymerase chain reaction-restriction fragment length polymorphism) and Tetra ARMS-PCR (tetra-primer Amplification Refractory Mutation System- PCR).

Results: Infertile group exhibited significantly lower BChE activity as compared to the fertile group (p≤0.01). In addition, notable genetic association of BChE variants with risk of male infertility was identified. BChE rs3495 showed significant correlation in dominant model (OR = 21.67, p = 0.0001) and allelic distribution (OR = 3.30, p = 0.0002) while rs1803274 showed robust association in all models (p = <0.0001).

Conclusion: This is the first study linking BChE variants and reduced BChE enzymatic activity with male infertility. These findings suggest BChE as a potential biomarker and therapeutic target for idiopathic infertility.