{"title":"NOX1 gene expression and hormonal alteration in hypothyroidism-associated female infertility.","authors":"Jineesh Valluvanga Chalil, Anbalagan Gnanavel, Sundaresan Saravana Kumar, Kesavi Durairaj, Jisha Anjali Madhavan Pillai, Jayasudha Edatholath, Priyanka Krishnan, Nitha Nellikuzhimalayil Parameswaran, Viji Krishnan, Dinesh Roy Divakaran","doi":"10.1515/hmbci-2025-0075","DOIUrl":null,"url":null,"abstract":"<p><strong>Objectives: </strong>To evaluate the association of NOX1 gene expression with reproductive hormonal changes in hypothyroid infertile women and assess their diagnostic performance.</p><p><strong>Methods: </strong>A case-control study was conducted among 150 infertile women with hypothyroidism and 150 healthy age-matched fertile controls. Hormonal (FSH, LH, prolactin) and molecular (NOX1 expression) parameters were measured using standardized assays including qRT-PCR. Group comparisons, Spearman's correlation analyses, scatterplot visualizations, and ROC curve evaluations were conducted to determine associations and diagnostic performance.</p><p><strong>Results: </strong>Hypothyroid infertile women exhibited significantly elevated FSH (19.9 ± 7.5 mIU/mL), LH (20.0 ± 7.6 mIU/mL), prolactin (21.9 ± 8.4 ng/mL), and TSH (7.2 ± 1.8 µIU/mL), along with reduced T3 (0.82 ± 0.21 ng/mL) and T4 (5.1 ± 1.2 μg/dL) compared to controls (p<0.01). NOX1 expression was markedly higher in peripheral blood (1.9 ± 0.9 vs. 1.0 ± 0.2; p<0.01). Moderate positive correlations were observed between NOX1 and FSH (r=0.5638), LH (r=0.5787), and prolactin (r=0.5968), all statistically significant (p<0.01). ROC analysis showed good diagnostic accuracy for FSH (AUC 0.801), LH (AUC 0.732), and prolactin (AUC 0.748), while NOX1 demonstrated superior discriminative performance (AUC 0.835) with 100 % specificity and a positive predictive value of 100 %.</p><p><strong>Conclusions: </strong>Hypothyroidism-associated infertility is characterized by combined endocrine imbalance and heightened oxidative stress. The strong discriminative ability and hormonal correlations of NOX1 expression suggest its potential use as a molecular biomarker to support infertility risk detection in thyroid-compromised women, providing a basis for oxidative-stress-targeted therapeutic strategies.</p>","PeriodicalId":13224,"journal":{"name":"Hormone Molecular Biology and Clinical Investigation","volume":" ","pages":"17-25"},"PeriodicalIF":1.9000,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Hormone Molecular Biology and Clinical Investigation","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1515/hmbci-2025-0075","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2026/3/1 0:00:00","PubModel":"eCollection","JCR":"Q4","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Objectives: To evaluate the association of NOX1 gene expression with reproductive hormonal changes in hypothyroid infertile women and assess their diagnostic performance.
Methods: A case-control study was conducted among 150 infertile women with hypothyroidism and 150 healthy age-matched fertile controls. Hormonal (FSH, LH, prolactin) and molecular (NOX1 expression) parameters were measured using standardized assays including qRT-PCR. Group comparisons, Spearman's correlation analyses, scatterplot visualizations, and ROC curve evaluations were conducted to determine associations and diagnostic performance.
Results: Hypothyroid infertile women exhibited significantly elevated FSH (19.9 ± 7.5 mIU/mL), LH (20.0 ± 7.6 mIU/mL), prolactin (21.9 ± 8.4 ng/mL), and TSH (7.2 ± 1.8 µIU/mL), along with reduced T3 (0.82 ± 0.21 ng/mL) and T4 (5.1 ± 1.2 μg/dL) compared to controls (p<0.01). NOX1 expression was markedly higher in peripheral blood (1.9 ± 0.9 vs. 1.0 ± 0.2; p<0.01). Moderate positive correlations were observed between NOX1 and FSH (r=0.5638), LH (r=0.5787), and prolactin (r=0.5968), all statistically significant (p<0.01). ROC analysis showed good diagnostic accuracy for FSH (AUC 0.801), LH (AUC 0.732), and prolactin (AUC 0.748), while NOX1 demonstrated superior discriminative performance (AUC 0.835) with 100 % specificity and a positive predictive value of 100 %.
Conclusions: Hypothyroidism-associated infertility is characterized by combined endocrine imbalance and heightened oxidative stress. The strong discriminative ability and hormonal correlations of NOX1 expression suggest its potential use as a molecular biomarker to support infertility risk detection in thyroid-compromised women, providing a basis for oxidative-stress-targeted therapeutic strategies.
期刊介绍:
Hormone Molecular Biology and Clinical Investigation (HMBCI) is dedicated to the provision of basic data on molecular aspects of hormones in physiology and pathophysiology. The journal covers the treatment of major diseases, such as endocrine cancers (breast, prostate, endometrium, ovary), renal and lymphoid carcinoma, hypertension, cardiovascular systems, osteoporosis, hormone deficiency in menopause and andropause, obesity, diabetes, brain and related diseases, metabolic syndrome, sexual dysfunction, fetal and pregnancy diseases, as well as the treatment of dysfunctions and deficiencies. HMBCI covers new data on the different steps and factors involved in the mechanism of hormone action. It will equally examine the relation of hormones with the immune system and its environment, as well as new developments in hormone measurements. HMBCI is a blind peer reviewed journal and publishes in English: Original articles, Reviews, Mini Reviews, Short Communications, Case Reports, Letters to the Editor and Opinion papers. Ahead-of-print publishing ensures faster processing of fully proof-read, DOI-citable articles.