Analysis of the potential regulatory mechanisms of female and latent genital tuberculosis affecting ovarian reserve function using untargeted metabolomics.


Journal

Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288

Informations de publication

Date de publication:
25 04 2024
Historique:
received: 22 02 2024
accepted: 19 04 2024
medline: 26 4 2024
pubmed: 26 4 2024
entrez: 25 4 2024
Statut: epublish

Résumé

Female and latent genital tuberculosis (FGTB and LGTB) in young women may lead to infertility by damaging ovarian reserve function, but the regulatory mechanisms remain unclear. In this study, we investigated the effects of FGTB and LGTB on ovarian reserve function and potential regulatory mechanisms by untargeted metabolomics of follicular fluid, aiming to provide insights for the clinical management and treatment approaches for afflicted women. We recruited 19 patients with FGTB, 16 patients with LGTB, and 16 healthy women as a control group. Clinical data analysis revealed that both the FGTB and LGTB groups had significantly lower ovarian reserve marker levels compared to the control group, including lower anti-Müllerian hormone levels (FGTB: 0.82 [0.6, 1.1] μg/L; LGTB: 1.57 [1.3, 1.8] μg/L vs. control: 3.29 [2.9, 3.5] μg/L), reduced antral follicular counts (FGTB: 6 [5.5, 9.5]; LGTB: 10.5 [7, 12.3] vs. control: 17 [14.5, 18]), and fewer retrieved oocytes (FGTB: 3 [2, 5]; LGTB: 8 [4, 8.3] vs. control: 14.5 [11.5, 15.3]). Conversely, these groups exhibited higher ovarian response marker levels, such as longer gonadotropin treatment days (FGTB: 12 [10.5, 12.5]; LGTB: 11 [10.8, 11.3] vs. control: 10 [8.8, 10]) and increased gonadotropin dosage requirements (FGTB: 3300 [3075, 3637.5] U; LGTB: 3037.5 [2700, 3225] U vs. control: 2531.25 [2337.5, 2943.8] U). All comparisons were statistically significant at P < 0.05. The results suggested that FGTB and LGTB have adverse effects on ovarian reserve and response. Untargeted metabolomic analysis identified 92 and 80 differential metabolites in the control vs. FGTB and control vs. LGTB groups, respectively. Pathway enrichment analysis revealed significant alterations in metabolic pathways in the FGTB and LGTB groups compared to the control group (P < 0.05), with specific changes noted in galactose metabolism, biotin metabolism, steroid hormone biosynthesis, and nicotinate and nicotinamide metabolism in the FGTB group, and caffeine metabolism, primary bile acid biosynthesis, steroid hormone biosynthesis, and glycerophospholipid metabolism in the LGTB group. The analysis of metabolic levels has revealed the potential mechanisms by which FGTB and LGTB affect ovarian reserve function, namely through alterations in metabolic pathways. The study emphasizes the importance of comprehending the metabolic alterations associated with FGTB and LGTB, which is of considerable relevance for the clinical management and therapeutic approaches in afflicted women.

Identifiants

pubmed: 38664479
doi: 10.1038/s41598-024-60167-7
pii: 10.1038/s41598-024-60167-7
doi:

Substances chimiques

Anti-Mullerian Hormone 80497-65-0
Biomarkers 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

9519

Subventions

Organisme : Inner Mongolia Autonomous Region Science and Technology Plan Project
ID : 2022YFSH0067
Organisme : Inner Mongolia Autonomous Region Science and Technology Plan Project
ID : 2021GG0389
Organisme : Inner Mongolia Medical University Youth Project
ID : YKD2024QN004
Organisme : Talent Introduction Project of the Inner Mongolia Autonomous Region
ID : EP2100003598

Informations de copyright

© 2024. The Author(s).

Références

Natarajan, A., Beena, P. M., Devnikar, A. V. & Mali, S. A systemic review on tuberculosis. Indian J. Tuberc. 67, 295–311. https://doi.org/10.1016/j.ijtb.2020.02.005 (2020).
doi: 10.1016/j.ijtb.2020.02.005 pubmed: 32825856
Bagcchi, S. WHO’s global tuberculosis report 2022. Lancet Microbe 4, e20. https://doi.org/10.1016/S2666-5247(22)00359-7 (2023).
doi: 10.1016/S2666-5247(22)00359-7 pubmed: 36521512
Grace, G. A., Devaleenal, D. B. & Natrajan, M. Genital tuberculosis in females. Indian J. Med. Res. 145, 425–436. https://doi.org/10.4103/ijmr.IJMR_1550_15 (2017).
doi: 10.4103/ijmr.IJMR_1550_15 pubmed: 28862174 pmcid: 5663156
Parvez, R. et al. Prevalence of female genital tuberculosis, its risk factors and associated clinical features among the women of Andaman Islands, India: A community-based study. Public Health 148, 56–62. https://doi.org/10.1016/j.puhe.2017.03.001 (2017).
doi: 10.1016/j.puhe.2017.03.001 pubmed: 28404534
Sharma, J. B. Current diagnosis and management of female genital tuberculosis. J. Obstet. Gynaecol. India 65, 362–371. https://doi.org/10.1007/s13224-015-0780-z (2015).
doi: 10.1007/s13224-015-0780-z pubmed: 26663993 pmcid: 4666212
Tjahyadi, D. et al. Female genital tuberculosis: Clinical presentation, current diagnosis, and treatment. Infect. Dis. Obstet. Gynecol. 2022, 3548190. https://doi.org/10.1155/2022/3548190 (2022).
doi: 10.1155/2022/3548190 pubmed: 36438172 pmcid: 9699775
Fatima, T. et al. Female genital tuberculosis in Pakistan—A retrospective review of 10-year laboratory data and analysis of 32 cases. Int. J. Mycobacteriol. 10, 66–70. https://doi.org/10.4103/ijmy.ijmy_6_21 (2021).
doi: 10.4103/ijmy.ijmy_6_21 pubmed: 33707374
Chaman-Ara, K., Bahrami, M. A., Moosazadeh, M. & Bahrami, E. Prevalence of infertility in women with genital tuberculosis: A systematic review and meta-analysis. Indones. J. Biomed. Sci. 11, 21–27 (2017).
doi: 10.15562/ijbs.v11i1.133
Das, P., Ahuja, A. & Gupta, S. D. Incidence, etiopathogenesis and pathological aspects of genitourinary tuberculosis in India: A journey revisited. Indian J. Urol. 24, 356–361. https://doi.org/10.4103/0970-1591.42618 (2008).
doi: 10.4103/0970-1591.42618 pubmed: 19468469 pmcid: 2684356
Ishrat, S. & Fatima, P. Genital tuberculosis in the infertile women—An update. Mymensingh Med. J. 24, 215–220 (2015).
pubmed: 25725695
Shaheen, R., Subhan, F. & Tahir, F. Epidemiology of genital tuberculosis in infertile population. J. Pak. Med. Assoc. 56, 306–309 (2006).
pubmed: 16900710
Tzelios, C. et al. Female genital tuberculosis. Open Forum Infect. Dis. 9, 543. https://doi.org/10.1093/ofid/ofac543 (2022).
doi: 10.1093/ofid/ofac543
Richa, S., Anjali, K., Sonal, J. & Akrati, J. Analysis of the effect of female genital tuberculosis on ovarian reserve parameters. J. Hum. Reprod. Sci. 16, 125–131. https://doi.org/10.4103/jhrs.jhrs_36_23 (2023).
doi: 10.4103/jhrs.jhrs_36_23 pubmed: 37547096 pmcid: 10404021
Tripathy, S. N. & Tripathy, S. N. Infertility and pregnancy outcome in female genital tuberculosis. Int. J. Gynaecol. Obstet. 76, 159–163. https://doi.org/10.1016/s0020-7292(01)00525-2 (2002).
doi: 10.1016/s0020-7292(01)00525-2 pubmed: 11818110
Dai, W. et al. In vitro fertilization outcome in women with endometrial tuberculosis and tubal tuberculosis. Gynecol. Endocrinol. 36, 819–823. https://doi.org/10.1080/09513590.2019.1702639 (2020).
doi: 10.1080/09513590.2019.1702639 pubmed: 31847626
Sharma, J. B., Sharma, S., Sharma, E., Dharmendra, S. & Singh, S. Immune disturbances in female genital tuberculosis and latent genital tuberculosis. Am. J. Reprod. Immunol. 89, e13632. https://doi.org/10.1111/aji.13632 (2023).
doi: 10.1111/aji.13632 pubmed: 36494901
Houben, R. M. & Dodd, P. J. The global burden of latent tuberculosis infection: A re-estimation using mathematical modelling. PLoS Med. 13, e1002152. https://doi.org/10.1371/journal.pmed.1002152 (2016).
doi: 10.1371/journal.pmed.1002152 pubmed: 27780211 pmcid: 5079585
Khabibullina, N. F., Kutuzova, D. M., Burmistrova, I. A. & Lyadova, I. V. The biological and clinical aspects of a latent tuberculosis infection. Trop. Med. Infect. Dis. 7, 48. https://doi.org/10.3390/tropicalmed7030048 (2022).
doi: 10.3390/tropicalmed7030048 pubmed: 35324595 pmcid: 8955876
Bhanothu, V., Theophilus, J. P., Reddy, P. K. & Rozati, R. Occurrence of female genital tuberculosis among infertile women: a study from a tertiary maternal health care research centre in South India. Eur. J. Clin. Microbiol. Infect. Dis. 33, 1937–1949. https://doi.org/10.1007/s10096-014-2164-1 (2014).
doi: 10.1007/s10096-014-2164-1 pubmed: 24894340
Bagchi, B., Chatterjee, S. & Gon Chowdhury, R. Role of latent female genital tuberculosis in recurrent early pregnancy loss: A retrospective analysis. Int. J. Reprod. Biomed. 17, 929–934. https://doi.org/10.18502/ijrm.v17i12.5799 (2019).
doi: 10.18502/ijrm.v17i12.5799 pubmed: 32095740 pmcid: 6943800
Jirge, P. R., Chougule, S. M., Keni, A., Kumar, S. & Modi, D. Latent genital tuberculosis adversely affects the ovarian reserve in infertile women. Hum. Reprod. 33, 1262–1269. https://doi.org/10.1093/humrep/dey117 (2018).
doi: 10.1093/humrep/dey117 pubmed: 29897442
Soussis, I., Trew, G., Matalliotakis, I., Margara, R. & Winston, R. M. In vitro fertilization treatment in genital tuberculosis. J. Assist. Reprod. Genet. 15, 378–380. https://doi.org/10.1023/A:1022533016670 (1998).
doi: 10.1023/A:1022533016670 pubmed: 9673882 pmcid: 3455018
Jindal, U. N. An algorithmic approach to female genital tuberculosis causing infertility. Int. J. Tuberc. Lung Dis. 10, 1045–1050 (2006).
pubmed: 16964799
Dahiya, B., Kamra, E., Alam, D., Chauhan, M. & Mehta, P. K. Insight into diagnosis of female genital tuberculosis. Expert. Rev. Mol. Diagn. 22, 625–642. https://doi.org/10.1080/14737159.2022.2016395 (2022).
doi: 10.1080/14737159.2022.2016395 pubmed: 34882522
Charalambous, S. et al. Scaling up evidence-based approaches to tuberculosis screening in prisons. Lancet Public Health 8, e305–e310. https://doi.org/10.1016/S2468-2667(23)00002-6 (2023).
doi: 10.1016/S2468-2667(23)00002-6 pubmed: 36780916
Schito, M. et al. Perspectives on advances in tuberculosis diagnostics, drugs, and vaccines. Clin. Infect. Dis. 61, S102-118. https://doi.org/10.1093/cid/civ609 (2015).
doi: 10.1093/cid/civ609 pmcid: 4583570
Moiseeva, A. V. et al. Genetic determination of the ovarian reserve: A literature review. J. Ovarian Res. 14, 102. https://doi.org/10.1186/s13048-021-00850-9 (2021).
doi: 10.1186/s13048-021-00850-9 pubmed: 34362406 pmcid: 8349022
Steiner, A. Z. et al. Association between biomarkers of ovarian reserve and infertility among older women of reproductive age. JAMA 318, 1367–1376. https://doi.org/10.1001/jama.2017.14588 (2017).
doi: 10.1001/jama.2017.14588 pubmed: 29049585 pmcid: 5744252
Jiang, W. et al. Analysis of relative factors and prediction model for optimal ovarian response with gonadotropin-releasing hormone antagonist protocol. Front. Endocrinol. (Lausanne) 13, 1030201. https://doi.org/10.3389/fendo.2022.1030201 (2022).
doi: 10.3389/fendo.2022.1030201 pubmed: 36457552
Butts, S. F. & Seifer, D. B. Racial and ethnic differences in reproductive potential across the life cycle. Fertil. Steril. 93, 681–690. https://doi.org/10.1016/j.fertnstert.2009.10.047 (2010).
doi: 10.1016/j.fertnstert.2009.10.047 pubmed: 19939362
Liu, L. et al. Machine learning-based modeling of ovarian response and the quantitative evaluation of comprehensive impact features. Diagnostics (Basel) 12, 492. https://doi.org/10.3390/diagnostics12020492 (2022).
doi: 10.3390/diagnostics12020492 pubmed: 35204580
Liu, L. et al. Follicular dynamics of glycerophospholipid and sphingolipid metabolisms in polycystic ovary syndrome patients. J. Steroid. Biochem. Mol. Biol. 185, 142–149. https://doi.org/10.1016/j.jsbmb.2018.08.008 (2019).
doi: 10.1016/j.jsbmb.2018.08.008 pubmed: 30121347
Wallace, M. et al. An investigation into the relationship between the metabolic profile of follicular fluid, oocyte developmental potential, and implantation outcome. Fertil. Steril. 97, 1078–1084. https://doi.org/10.1016/j.fertnstert.2012.01.122 (2012).
doi: 10.1016/j.fertnstert.2012.01.122 pubmed: 22365382
Azman, K. F. & Zakaria, R. D-Galactose-induced accelerated aging model: An overview. Biogerontology 20, 763–782. https://doi.org/10.1007/s10522-019-09837-y (2019).
doi: 10.1007/s10522-019-09837-y pubmed: 31538262
Fateh, M., Ben-Rafael, Z., Benadiva, C. A., Mastroianni, L. Jr. & Flickinger, G. L. Cortisol levels in human follicular fluid. Fertil. Steril. 51, 538–541. https://doi.org/10.1016/s0015-0282(16)60572-1 (1989).
doi: 10.1016/s0015-0282(16)60572-1 pubmed: 2920855
Xiao, H. et al. Cortisol safeguards oogenesis by promoting follicular cell survival. Sci. China Life Sci. 65, 1563–1577. https://doi.org/10.1007/s11427-021-2051-0 (2022).
doi: 10.1007/s11427-021-2051-0 pubmed: 35167018
Morris, F. L. & Wark, J. D. An effective, economic way of monitoring menstrual cycle hormones in at risk female athletes. Med. Sci. Sports Exerc. 33, 9–14. https://doi.org/10.1097/00005768-200101000-00003 (2001).
doi: 10.1097/00005768-200101000-00003 pubmed: 11194117
Thatcher, S. S., Boyle, H. P., Glasier, A. F., Hillier, S. G. & Baird, D. T. A comparison of dosages of norethisterone for synchronization of cycles in a fixed regimen of follicular augmentation and in vitro fertilization. Fertil. Steril. 49, 848–853. https://doi.org/10.1016/s0015-0282(16)59895-1 (1988).
doi: 10.1016/s0015-0282(16)59895-1 pubmed: 3360173
Smith, L. P. et al. The bile acid synthesis pathway is present and functional in the human ovary. PLoS One 4, e7333. https://doi.org/10.1371/journal.pone.0007333 (2009).
doi: 10.1371/journal.pone.0007333 pubmed: 19806215 pmcid: 2752198
Takae, K. et al. Evidence for the involvement of FXR signaling in ovarian granulosa cell function. J. Reprod. Dev. 65, 47–55. https://doi.org/10.1262/jrd.2018-054 (2019).
doi: 10.1262/jrd.2018-054 pubmed: 30449821
Yang, X. et al. Profile of bile acid metabolomics in the follicular fluid of PCOS patients. Metabolites 11, 845. https://doi.org/10.3390/metabo11120845 (2021).
doi: 10.3390/metabo11120845 pubmed: 34940603 pmcid: 8703527
Wen, X. et al. Lipidomic components alterations of human follicular fluid reveal the relevance of improving clinical outcomes in women using progestin-primed ovarian stimulation compared to short-term protocol. Med. Sci. Monit. 24, 3357–3365. https://doi.org/10.12659/MSM.906602 (2018).
doi: 10.12659/MSM.906602 pubmed: 29783268 pmcid: 5989624
Mir, N. & Pal, L. Genital tuberculosis, infertility and assisted reproduction. Curr. Opin. Obstet. Gynecol. 35, 263–269. https://doi.org/10.1097/GCO.0000000000000866 (2023).
doi: 10.1097/GCO.0000000000000866 pubmed: 36912346
de la Barca, J. M. C. et al. Targeted metabolomics reveals reduced levels of polyunsaturated choline plasmalogens and a smaller dimethylarginine/arginine ratio in the follicular fluid of patients with a diminished ovarian reserve. Hum. Reprod. 32, 2269–2278. https://doi.org/10.1093/humrep/dex303 (2017).
doi: 10.1093/humrep/dex303 pubmed: 29040513
Bettencourt, I. A. & Powell, J. D. Targeting metabolism as a novel therapeutic approach to autoimmunity, inflammation, and transplantation. J. Immunol. 198, 999–1005. https://doi.org/10.4049/jimmunol.1601318 (2017).
doi: 10.4049/jimmunol.1601318 pubmed: 28115589
Bozdag, G. & Yildiz, B. O. Interventions for the metabolic dysfunction in polycystic ovary syndrome. Steroids 78, 777–781. https://doi.org/10.1016/j.steroids.2013.04.008 (2013).
doi: 10.1016/j.steroids.2013.04.008 pubmed: 23624033
Maleki-Saghooni, N., Amirian, M., Sadeghi, R. & Latifnejad Roudsari, R. Effectiveness of infertility counseling on pregnancy rate in infertile patients undergoing assisted reproductive technologies: a systematic review and meta-analysis. Int. J. Reprod. Biomed. 15, 391–402 (2017).
pubmed: 29177241 pmcid: 5601930

Auteurs

Zhimin Wang (Z)

Reproductive Medicine Center, Affiliated Hospital of Inner Mongolia Medical University, Hohhot, 010050, People's Republic of China.

Xueyan Zhang (X)

Reproductive Medicine Center, Affiliated Hospital of Inner Mongolia Medical University, Hohhot, 010050, People's Republic of China.

Bai Dai (B)

Reproductive Medicine Center, Affiliated Hospital of Inner Mongolia Medical University, Hohhot, 010050, People's Republic of China.

Debang Li (D)

Reproductive Medicine Center, Affiliated Hospital of Inner Mongolia Medical University, Hohhot, 010050, People's Republic of China.

Xiujuan Chen (X)

Reproductive Medicine Center, Affiliated Hospital of Inner Mongolia Medical University, Hohhot, 010050, People's Republic of China. 1431272841@qq.com.

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female
Humans United States Aged Cross-Sectional Studies Medicare Part C
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH