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pmid:36130055
Defensins: defenders of human reproductive health.
Yu-Jia Zhai · Ying Feng · Xue Ma · Fang Ma
Human reproduction update · 2023 doi:10.1093/humupd/dmac032
Paper
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Experiment
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Data
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Complete file
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Among male infertility factors, 13-15% of male infertility is related to infection. Defensins are cationic antibacterial and antiviral peptides, classified into α-defensins, β-defensins and θ-defensins. Humans only have α-defensins and β-defensins. Apart from their direct antimicrobial functions, defensins have an immunomodulatory function and are involved in many physiological processes. Studies have shown that defensins are widely distributed in the female reproductive tract (FRT) and male reproductive tract (MRT), playing a dual role of host defence and fertility protection. However, to our knowledge, the distribution, regulation and function of defensins in the reproductive tract and their relation to reproduction have not been reviewed.\nOBJECTIVE AND RATIONALE: This review summarizes the expression, distribution and regulation of defensins in the reproductive tracts to reveal the updated research on the dual role of defensins in host defence and the protection of fertility.\nSEARCH METHODS: A systematic search was conducted in PubMed using the related keywords through April 2022. Related data from original researches and reviews were integrated to comprehensively review the current findings and understanding of defensins in the human reproductive system. Meanwhile, female and male transcriptome data in the GEO database were screened to analyze defensins in the human reproductive tracts.\nOUTCOMES: Two transcriptome databases from the GEO database (GSE7307 and GSE150852) combined with existing researches reveal the expression levels and role of the defensins in the reproductive tracts. In the FRT, a high expression level of α-defensin is found, and the expression levels of defensins in the vulva and vagina are higher than those in other organs. The expression of defensins in the endometrium varies with menstrual cycle stages and with microbial invasion. Defensins also participate in the local immune response to regulate the risk of spontaneous preterm birth. In the MRT, a high expression level of β-defensins is also found. It is mainly highly expressed in the epididymal caput and corpus, indicating that defensins play an important role in sperm maturation. The expression of defensins in the MRT varies with androgen levels, age and the status of microbial invasion. They protect the male reproductive system from bacterial infections by neutralizing lipopolysaccharide and downregulating pro-inflammatory cytokines. In addition, animal and clinical studies have shown that defensins play an important role in sperm maturation, motility and fertilization.\nWIDER IMPLICATIONS: As a broad-spectrum antimicrobial peptide without drug resistance, defensin has great potential for developing new natural antimicrobial treatments for reproductive tract infections. However, increasing evidence has shown that defensins can not only inhibit microbial invasion but can also promote the invasion and adhesion of some microorganisms in certain biological environments, such as human immunodeficiency virus. Therefore, the safety of defensins as reproductive tract anti-infective drugs needs more in-depth research. In addition, the modulatory role of defensins in fertility requires more in-depth research since the current conclusions are based on small-size samples. At present, scientists have made many attempts at the clinical transformation of defensins. However, defensins have problems such as poor stability, low bioavailability and difficulties in their synthesis. Therefore, the production of safe, effective and low-cost drugs remains a challenge.", "claims": [{"id": "claim-data-access", "statement": "The data underlying this article are available in GEO database, and can be accessed with GeneChip array data GSE7307 and high-throughput sequencing data GSE150852.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36130055", "locator": "sections[32] \"Data availability\" paragraph 2", "quote": "The data underlying this article are available in GEO database, and can be accessed with GeneChip array data GSE7307 and high-throughput sequencing data GSE150852."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Two GEO transcriptome databases combined with existing research revealed defensin expression levels and roles in the female and male reproductive tracts.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:36130055", "locator": "sections[0] \"Abstract\" paragraph 4", "quote": "Two transcriptome databases from the GEO database (GSE7307 and GSE150852) combined with existing researches reveal the expression levels and role of the defensins in the reproductive tracts."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Two GEO transcriptome databases combined with existing research revealed defensin expression levels and roles in the female and male reproductive tracts.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:36130055"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE150852"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "complete", "blocked_on": null, "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE150852"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:36130055", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1093/humupd/dmac032", "sha256": 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