PMID- 35111159 OWN - NLM STAT- MEDLINE DCOM- 20220223 LR - 20220429 IS - 1664-3224 (Electronic) IS - 1664-3224 (Linking) VI - 12 DP - 2021 TI - The Association of HLA-G Gene Polymorphism and Its Soluble Form With Male Infertility. PG - 791399 LID - 10.3389/fimmu.2021.791399 [doi] LID - 791399 AB - Successful reproduction depends on many factors. Male factors contribute to infertility in approximately 50% of couples who fail to conceive. Seminal plasma consists of secretions from different accessory glands containing a mixture of various cytokines, chemokines, and growth factors, which together can induce a local immune response that might impact on a male's as well as a female's fertility. Human leukocyte antigen (HLA)-G expression has been suggested as an immunomodulatory molecule that influences pregnancy outcome. The HLA-G gene encodes either membrane-bound or/and soluble proteins. The aim of this study was the evaluation of HLA-G polymorphisms and their impact on soluble HLA-G (sHLA-G) production. We tested the HLA-G polymorphism in three positions: rs1632947: c.-964G>A; rs1233334: c.-725G>C/T in the promoter region; rs371194629: c. *65_ *66insATTTGTTCATGCCT in the 3' untranslated region. We tested two cohorts of men: 663 who participated in in vitro fertilization (test material was blood or sperm), and 320 fertile controls who possessed children born after natural conception (test material was blood). Since 50% of men visiting assisted reproductive clinics have abnormal semen parameters, we wondered if men with normal sperm parameters differ from those with abnormal parameters in terms of HLA-G polymorphism and secretion of sHLA-G into semen. We found that certain rs1632947-rs1233334-rs371194629 HLA-G haplotypes and diplotypes were associated with male infertility, while others were protective. Normozoospermic men with the A-C-del haplotype and A-C-del/A-C-del diplotype secreted the most sHLA-G into semen (574.1 IU/mL and 1047.0 IU/mL, respectively), while those with the G-C-ins haplotype and G-C-ins/G-C-ins diplotype - the least (80.8 IU/mL and 75.7 IU/mL, respectively). Men with the remaining haplotypes/diplotypes secreted sHLA-G at an intermediate level. However, only in one haplotype, namely G-C-ins, did we observe strong significant differences in the concentration of sHLA-G in the semen of men with teratozoospermia compared to men with normal sperm parameters (p = 0.009). In conclusion, fertile men differ in the profile of HLA-G polymorphism from men participating in IVF. Among all HLA-G haplotypes, the most unfavorable for male fertility is the G-C-ins haplotype, which determines the secretion of the lowest concentration of the soluble HLA-G molecule. This haplotype may reduce sperm parameters. CI - Copyright (c) 2022 Piekarska, Radwan, Tarnowska, Wisniewski, Krasinski, Radwan, Wilczynski, Malinowski and Nowak. FAU - Piekarska, Karolina AU - Piekarska K AD - Department of Clinical Immunology, Laboratory of Immunogenetics and Tissue Immunology, Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland. FAU - Radwan, Pawel AU - Radwan P AD - Department of Reproductive Medicine, Gameta Hospital, Rzgow, Poland. FAU - Tarnowska, Agnieszka AU - Tarnowska A AD - Department of Clinical Immunology, Laboratory of Immunogenetics and Tissue Immunology, Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland. FAU - Wisniewski, Andrzej AU - Wisniewski A AD - Department of Clinical Immunology, Laboratory of Immunogenetics and Tissue Immunology, Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland. FAU - Krasinski, Rafal AU - Krasinski R AD - Department of Reproductive Medicine, Gameta Hospital, Rzgow, Poland. FAU - Radwan, Michal AU - Radwan M AD - Department of Reproductive Medicine, Gameta Hospital, Rzgow, Poland. AD - Faculty of Health Sciences, The State University of Applied Sciences in Plock, Plock, Poland. FAU - Wilczynski, Jacek R AU - Wilczynski JR AD - Department of Surgical and Oncological Gynecology, Medical University of Lodz, Lodz, Poland. FAU - Malinowski, Andrzej AU - Malinowski A AD - Department of Surgical, Endoscopic and Oncologic Gynecology, Polish Mothers' Memorial Hospital-Research Institute, Lodz, Poland. FAU - Nowak, Izabela AU - Nowak I AD - Department of Clinical Immunology, Laboratory of Immunogenetics and Tissue Immunology, Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20220117 PL - Switzerland TA - Front Immunol JT - Frontiers in immunology JID - 101560960 RN - 0 (HLA-G Antigens) SB - IM MH - Adult MH - Aged MH - Female MH - Fertilization in Vitro/methods MH - Gene Frequency/genetics MH - Genotype MH - HLA-G Antigens/*genetics MH - Haplotypes/genetics MH - Humans MH - Infertility, Male/*genetics MH - Male MH - Middle Aged MH - *Polymorphism, Genetic MH - Pregnancy MH - Pregnancy Outcome/genetics MH - Semen/metabolism MH - Young Adult PMC - PMC8801424 OTO - NOTNLM OT - HLA-G polymorphism OT - In vitro fertilization OT - male infertility OT - sHLA-G OT - semen COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2022/02/04 06:00 MHDA- 2022/02/24 06:00 PMCR- 2021/01/01 CRDT- 2022/02/03 05:33 PHST- 2021/10/08 00:00 [received] PHST- 2021/12/28 00:00 [accepted] PHST- 2022/02/03 05:33 [entrez] PHST- 2022/02/04 06:00 [pubmed] PHST- 2022/02/24 06:00 [medline] PHST- 2021/01/01 00:00 [pmc-release] AID - 10.3389/fimmu.2021.791399 [doi] PST - epublish SO - Front Immunol. 2022 Jan 17;12:791399. doi: 10.3389/fimmu.2021.791399. eCollection 2021.