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Can coronavirus disease 2019 affect male fertility or cause spontaneous abortion? A two-sample Mendelian randomization analysis

  • Yufeng Liang , Xueshan Ma , Chunli Liu , Xiuqing He , Tao Liu and Xiaoming Niu EMAIL logo
Published/Copyright: October 30, 2025
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Open Life Sciences
From the journal Open Life Sciences Volume 20 Issue 1

Abstract

To investigate the causal relationship between two adverse reproductive outcomes (male infertility and spontaneous abortion) and COVID-19 infection using Mendelian randomization (MR) analysis. A two-sample MR study was conducted to examine potential causal links between COVID-19 infection severity and reproductive outcomes, using large-scale genome-wide association study (GWAS) summary statistics from European-ancestry populations. GWAS summary statistics were analyzed for COVID-19 phenotypes (infection: n = 1,683,769; hospitalized: n = 1,557,411; very severe respiratory-confirmed: n = 1,388,342; critical illness: n = 10,056) and reproductive outcomes (spontaneous abortion: n = 98,453; male infertility: n = 73,479). Causal estimates were calculated using inverse variance weighted (IVW), weighted median, MR-Egger regression, and weighted mode methods. IVW analysis revealed no significant association between genetic susceptibility to COVID-19 infection and male infertility (odds ratio [OR] = 0.7668; 95% confidence interval [CI]: 0.3798–1.5484; p = 0.4590) or spontaneous abortion (OR = 0.9936; 95% CI: 0.8066–1.2241; p = 0.8518). Similar null associations between COVID-19 severity phenotypes (hospitalized, very severe respiratory-confirmed, and critical illness) and male infertility or spontaneous abortion were observed. Sensitivity analyses using alternative methods confirmed the absence of pleiotropy and heterogeneity. This two-sample MR analysis provides robust evidence against a causal relationship between COVID-19 and increased risks of male infertility or spontaneous abortion.

Graphical abstract

Mendelian randomization (MR) analysis reveals no causal effect of COVID-19 infection on male infertility or spontaneous abortion.

Keywords: COVID-19; Mendelian randomization; spontaneous abortion; male infertility; causal relationship

1 Introduction

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) was first identified in December 2019 during an outbreak of fatal pneumonia in Wuhan, China [1]. Subsequently, the World Health Organization officially named the disease caused by this novel coronavirus “coronavirus disease-2019 (COVID-19).” The ongoing COVID-19 pandemic has affected millions globally and continues to represent a significant public health challenge [2]. After recovery from the acute infection, up to 30% of COVID-19 survivors may develop post-COVID-19 syndrome [3], which is characterized by persistent symptoms and long-term sequelae.

The global impact of COVID-19 goes beyond respiratory complications, potentially affecting multiple organ systems. Although pulmonary involvement remains the predominant manifestation, an increasing body of evidence indicates that COVID-19 may trigger various systemic abnormalities, including potential testicular dysfunction [4]. Given the multi-organ impact of COVID-19, concerns have been raised about its potential effects on reproductive health. Recent studies have detected SARS-CoV-2 in semen samples, raising concerns about possible paternal transmission [5]. Several comprehensive reviews have explored the potential testicular damage associated with COVID-19 infection and its possible implications for male fertility [6]. A 2024 systematic review of 135 studies highlighted that SARS-CoV-2 infection transiently reduces sperm motility and morphology, though these parameters often recover within spermatogenic cycles, suggesting acute inflammatory effects rather than permanent damage [7]. Conversely, another 2024 systematic analysis reported hormonal alterations and impaired semen quality in convalescent men, yet found no viral RNA in semen, underscoring unresolved pathophysiological mechanisms [8]. Some researchers have proposed that mature spermatozoa may interact with the virus and potentially serve as viral vectors [9]. The primary cause of male infertility is compromised sperm quality, and COVID-19 may additionally disrupt the hypothalamic–pituitary–gonadal axis, which could further contribute to fertility impairment [6]. These globally heterogeneous findings highlight the urgency of clarifying causal relationships to inform public health policies and alleviate undue reproductive anxiety worldwide.

Similarly, as the global prevalence of COVID-19 continues to rise, data on its impact on pregnancy outcomes remain limited. Early meta-analyses suggested elevated risks of adverse pregnancy outcomes, including preterm birth, preeclampsia, cesarean delivery, and neonatal mortality [10]. However, large-scale cohort studies reported conflicting evidence on spontaneous abortion [11,12]. A systematic review of 42 studies (n = 438,548) found no significant increase in spontaneous abortion risk [11], whereas a retrospective cohort study (n = 193) documented nine cases of spontaneous abortion without establishing a causal link [12]. The paucity of robust data regarding COVID-19-associated spontaneous abortions during the first trimester hinders our understanding of early pregnancy complications. Notably, a case-control study (n = 225) confirmed COVID-19 does not predict early pregnancy loss [13], yet this inconsistency persists. This information gap has fueled public anxiety and the potential spread of media misinformation, which may influence pregnant women to consider elective termination without valid medical reasons [14]. Therefore, it is of paramount importance to determine the potential role of COVID-19 infection in spontaneous abortion.

Observational studies investigating the association between COVID-19 and reproductive outcomes are inherently constrained by potential confounding factors and reverse causality. Randomized controlled trials are unethical in this context. Mendelian randomization (MR) overcomes these limitations by using genetic variants as instrumental variables [15,16]. This approach leverages the random assortment of alleles to mimic a randomized trial, providing more robust causal inferences [15,16]. In this study, we employed a two-sample MR design to investigate the potential causal effects of COVID-19 on male infertility and spontaneous abortion. By utilizing genetic variants associated with COVID-19 as instrumental variables, we aimed to provide robust evidence regarding the potential impact of COVID-19 on reproductive outcomes. We hypothesized that there was no significant causal association between COVID-19 infection and an increased risk of male infertility or spontaneous abortion. Key findings and clinical implications were shown in graphical abstract.

2 Methods

2.1 Data sources

This study utilized publicly available summary-level data from large-scale genome-wide association studies (GWAS) consortia. The authors did not carry out any direct patient recruitment or selection procedures. Genetic association summary statistics for four COVID-19 severity phenotypes were retrieved from the Integrative Epidemiology Unit Open GWAS project (https://gwas.mrcieu.ac.uk/). For this MR study, the exposure datasets were defined by COVID-19 (ebi-a-GCST011073), COVID-19 hospitalized (ebi-a-GCST011083), COVID-19 very severe respiratory confirmed (ebi-a-GCST011075), and COVID-19 critical illness (ebi-a-GCST90013414). The outcome GWAS summary statistics for male infertility (finn-b-N14_MALEINFERT) and spontaneous abortion (finn-b-O15_ABORT_SPONTAN) were obtained from the FinnGen consortium Release R10 (https://www.finngen.fi/en). All exposure and outcome cases were of European descent. Detailed characteristics of the exposures and outcomes of GAWS are shown in Table 1.

Table 1

Characteristics of the GWASs used for the MR analyses

GWAS ID Phenotype Sample size Cases (n) Controls (n) SNPs (n) Population
ebi-a-GCST011073 COVID-19 1,683,748 38,984 1,644,784 8,660,177 European
ebi-a-GCST011083 COVID-19 (hospitalized) 1,557,411 8,316 1,549,095 8,110,403 European
ebi-a-GCST011075 COVID-19 (very severe respiratory-confirmed) 1,388,342 5,101 1,383,241 9,739,225 European
ebi-a-GCST90013414 COVID-19 (critical illness) 10,056 1,676 8,380 4,264,568 European
finn-b-O15_ABORT_SPONTAN Spontaneous abortion 98,453 9,113 89,340 16,379,138 European
finn-b-N14_MALEINFERT Male infertility 73,479 680 72,799 16,377,329 European

GWAS, genome-wide association study; SNP, single-nucleotide polymorphism.

2.2 Genetic instrument selection for COVID-19 phenotypes

An overview of the study design was presented in Figure 1. COVID-19 showed a strong association with seven single-nucleotide polymorphisms (SNPs; p < 5 × 10−8, linkage disequilibrium r 2 < 0.01). Both COVID-19 hospitalization and COVID-19 with very severe respiratory confirmation were associated with eight SNPs, whereas COVID-19 critical illness was related to five SNPs (p < 5 × 10−8, linkage disequilibrium r 2 < 0.01). Detailed information about the SNPs was provided in Table 2. All SNPs exhibited F-statistics >10, indicating strong instrument validity.

Figure 1 The core instrumental variable assumptions of MR study. SNP, single-nucleotide polymorphisms.
Figure 1

The core instrumental variable assumptions of MR study. SNP, single-nucleotide polymorphisms.

Table 2

Details of the genetic instrumental variables (SNPs) associated with each COVID-19 severity phenotype

SNP Effect allele Other allele β MAF SE p-value R 2 F
COVID-19
rs10936744 T C −0.0626 0.3588 0.0100 3.51 × 10−10 0.0018 3034.522
rs12482060 G C 0.06195 0.3375 0.0105 3.96 × 10−09 0.0017 2884.842
rs17078348 G A 0.09208 0.0997 0.0161 1.20 × 10−08 0.0015 2559.18
rs2271616 T G 0.15634 0.1181 0.0150 3.61 × 10−25 0.0051 8529.123
rs4971066 G T −0.0767 0.1777 0.0134 1.02 × 10−08 0.0017 2894.5
rs643434 A G 0.1013 0.371 0.0101 1.29 × 10−23 0.0049 8025.465
rs757405 A T 0.06892 0.7092 0.0107 1.64 × 10−10 0.0020 3292.98
COVID-19 (hospitalized)
rs10860891 A C −0.1828 0.8547 0.0331 3.43 × 10−08 0.0083 13034.19
rs111837807 C T 0.2155 0.1004 0.0343 3.22 × 10−10 0.0084 13175.56
rs13050728 C T −0.1861 0.6382 0.0239 6.72 × 10−15 0.0160 25313.54
rs1859330 A G 0.1561 0.6979 0.0226 4.91 × 10−12 0.0103 16168.43
rs2109069 A G 0.1873 0.322 0.0236 1.96 × 10−15 0.0153 24226.89
rs35081325 T A 0.5462 0.0859 0.0354 7.93 × 10−54 0.0468 76527.59
rs41264915 G A −0.2049 0.0817 0.0358 1.02 × 10−08 0.0063 9870.101
COVID-19 (very severe respiratory-confirmed)
rs10860891 A C −0.2395 0.8855 0.0397 1.64 × 10−09 0.0116 16338.49
rs111837807 C T 0.2945 0.0996 0.0428 5.66 × 10−12 0.0156 21938.16
rs13050728 C T −0.2001 0.6627 0.0286 2.44 × 10−12 0.0179 25304.5
rs2109069 A G 0.2566 0.3287 0.0281 6.12 × 10−20 0.0291 41549.14
rs2237698 T C 0.2366 0.0897 0.0397 2.41 × 10−09 0.0091 12809.17
rs2384074 T C 0.1982 0.6756 0.0282 2.10 × 10−12 0.0172 24324.66
rs35081325 T A 0.6262 0.0753 0.0445 5.75 × 10−45 0.0546 80192.84
rs77534576 T C 0.45975 0.0347 0.1255 8.52 × 10−10 0.0142 19941.36
COVID-19 (critical illness)
rs10735079 A G 0.2578 0.3514 0.0457 1.65 × 10−08 0.0303 314.1043
rs143334143 A G 0.6151 0.0823 0.0716 8.82 × 10−18 0.0572 609.4227
rs2109069 A G 0.3056 0.2993 0.0440 3.98 × 10−12 0.0392 409.8913
rs2236757 G A −0.2511 0.2911 0.0461 5.00 × 10−08 0.0260 268.6214
rs73064425 T C 0.7628 0.0695 0.0670 4.77 × 10−30 0.0753 818.2214

SNP, single-nucleotide polymorphisms; β, effect size; MAF, minor allele frequency; SE, standard error of β; R 2, the proportion of the variability of the exposure explained by instrumental variables.

2.3 Outcome data acquisition and harmonization

For each COVID-19-associated SNP, effect sizes and standard errors were extracted. Incompatible alleles and palindromic SNPs were excluded to ensure strand alignment.

2.4 Confounding SNP exclusion

To control for potential confounding factors, the PhenoScanner database (http://www.phenoscanner.medschl.cam.ac.uk) was employed to identify secondary phenotypes associated with COVID-19-related SNPs. SNPs were excluded if they were significantly associated with known confounders of reproductive outcomes, such as thrombophilia, autoimmune diseases, and endocrine disorders [17,18,19,20]. Specifically, rs643434, associated with thrombosis (p = 7 × 10−63) and deep vein thrombosis (p = 1 × 10−173), and rs111837807, linked to type 1 diabetes (p = 2 × 10⁻11), type 2 diabetes (p = 7 × 10⁻20), and hypothyroidism (p = 1 × 10⁻10), met these criteria and were excluded prior to conducting the MR analysis. The remaining SNPs showed no significant association with confounders of male infertility or spontaneous abortion.

2.5 Statistical analysis

The primary causal estimates for the relationship between COVID-19 and male infertility or spontaneous abortion were derived using the inverse variance weighted (IVW) method, which operates under the assumption of no horizontal pleiotropy. The main findings were based on an inverse variance-weighted meta-analysis of the Wald ratios for individual SNPs, predicated on the assumption that no unmeasured confounders or alternative pathways influenced the outcomes through the genetic instruments [21]. To complement the IVW estimates, MR-Egger regression, weighted median, and weighted mode methods were employed. These methods served as robustness checks to validate the primary findings.

Sensitivity analyses were carried out to evaluate potential pleiotropy and heterogeneity, as their presence could significantly bias the MR estimates if not properly accounted for. Horizontal pleiotropy was assessed using Cochran’s Q statistic derived from the IVW method, which tests for heterogeneity among the genetic instruments. Directional pleiotropy was evaluated through the intercept term in MR-Egger regression, with a p-value of <0.05 indicating its presence [22]. Furthermore, the MR-Pleiotropy Residual Sum and Outlier (MR-PRESSO) method was applied to detect and rectify horizontal pleiotropy by identifying and eliminating outliers [23]. The MR-PRESSO procedure comprised three sequential steps: identification of horizontal pleiotropy, removal of outlier SNPs to correct for pleiotropic effects, and comparison of causal estimates before and after outlier removal to determine statistically significant differences. MR-Egger regression provides more precise and less biased estimates compared to IVW method when the proportion of genetic variants exhibiting horizontal pleiotropy was below 10% [24]. A leave-one-out analysis was performed to evaluate whether the MR estimates were disproportionately influenced by any single SNP. The MR study methodology was shown in Figure 2. All analyses were performed using MRPRESSO (version 0.6.4) and the TwoSampleMR (version 0.6.4) package in R (version 4.3.1).

Figure 2 MR study methodology to reveal the causative influence of coronavirus disease-2019 (COVID-19) on spontaneous abortion and male infertility. IVW, inverse variance weighted; MR, Mendelian randomization; MR-PRESSO, MR Pleiotropy RESidual Sum and Outlier; SNP, single-nucleotide polymorphisms.
Figure 2

MR study methodology to reveal the causative influence of coronavirus disease-2019 (COVID-19) on spontaneous abortion and male infertility. IVW, inverse variance weighted; MR, Mendelian randomization; MR-PRESSO, MR Pleiotropy RESidual Sum and Outlier; SNP, single-nucleotide polymorphisms.

  1. Ethical approval: As this study involved the reanalysis of previously obtained and published data, no additional ethical approval was required.

3 Results

3.1 Impact of COVID-19 on spontaneous abortion

After excluding SNPs associated with thrombus formation (rs643434), hypothyroidism/diabetes (rs111837807), palindromic SNPs with intermediate allele frequencies, and incompatible alleles, the final counts of SNPs retained for each COVID-19 phenotype in the MR analyses were as follows: (1) for COVID-19 infection, six SNPs were retained; (2) for COVID-19 hospitalized, six SNPs were retained; (3) for COVID-19 very severe respiratory-confirmed, seven SNPs were retained; and (4) for COVID-19 critical illness, five SNPs were retained. We observed no significant association between COVID-19 infection and spontaneous abortion risk (IVW: odds ratio [OR] = 0.9936, 95% confidence interval [CI]: 0.8066–1.2241, p = 0.8518; Table 3). Consistent null associations were found across all COVID-19 severity phenotypes: hospitalized: OR = 1.0031, 95% CI = 0.9343–1.0770, p = 0.9314; very severe respiratory-confirmed: OR = 1.0012, 95% CI = 0.9478–1.0576, p = 0.9656; critical illness: OR = 1.0009, 95% CI = 0.9557–1.0481, p = 0.9703 (Table 3).

Table 3

MR estimates of the causal effect of COVID-19 phenotypes on the risk of spontaneous abortion

Outcome Method OR 95% CI p-value
COVID-19 IVW 0.9936 0.8066–1.2241 0.8518
MR Egger 1.6410 0.7899–3.4092 0.2087
Weighted median 1.1349 0.8721–1.4767 0.5074
Weighted mode 1.1799 0.8013–1.7375 0.4351
COVID-19 (hospitalized) IVW 1.0031 0.9343–1.0770 0.9314
MR Egger 1.0671 0.9081–1.2539 0.4744
Weighted median 1.0176 0.9358–1.1065 0.6832
Weighted mode 1.0258 0.9315–1.1297 0.6266
COVID-19 (very severe respiratory confirmed) IVW 1.0012 0.9478–1.0576 0.9656
MR Egger 1.0511 0.9194–1.2015 0.4985
Weighted median 1.0082 0.9437–1.0771 0.8090
Weighted mode 1.0230 0.9429–1.1100 0.6039
COVID-19 (critical illness) IVW 1.0009 0.9557–1.0481 0.9703
MR Egger 1.0219 0.9179–1.1377 0.7185
Weighted median 1.0188 0.9619–1.0791 0.5254
Weighted mode 1.0217 0.9534–1.0949 0.5758

IVW, inverse variance weighted; OR: odds ratio; CI: confidence interval.

Sensitivity analyses using MR-Egger regression, weighted median, and weighted mode approaches yielded consistent results (all p > 0.05; Table 3 and Figure 3). No significant heterogeneity (Cochran’s Q p > 0.05) or directional pleiotropy (MR-Egger intercept p > 0.05) was detected (Table 4). The leave-one-out analysis confirmed that no single SNP had a disproportionate influence on the estimates (Figure S1).

Figure 3 MR analysis of COVID-19 on spontaneous abortion. SNP, single-nucleotide polymorphisms; IVW, inverse variance weighted; MR, Mendelian randomization; OR: odds ratio; CI: confidence interval.
Figure 3

MR analysis of COVID-19 on spontaneous abortion. SNP, single-nucleotide polymorphisms; IVW, inverse variance weighted; MR, Mendelian randomization; OR: odds ratio; CI: confidence interval.

Table 4

Sensitivity analyses for the MR of COVID-19 phenotypes on spontaneous abortion, including Cochran’s Q test for heterogeneity and the MR-Egger intercept test for pleiotropy

Exposure Q/intercept p-value
COVID-19
Cochran Q test Q
MR Egger 2.3225 0.6767
IVW 4.2910 0.5083
Pleiotropy-test Intercept
−0.04036 0.2333
COVID-19 (hospitalized)
Cochran Q test Q
MR Egger 1.5374 0.8200
IVW 2.2370 0.8155
Pleiotropy-test Intercept
−0.0162 0.4500
COVID-19 (very severe respiratory -confirmed)
Cochran Q test Q
MR Egger 1.3158 0.9333
IVW 1.9245 0.9265
Pleiotropy-test Intercept
−0.0156 0.4706
COVID-19 (critical illness)
Cochran Q test Q
MR Egger 2.1641 0.5390
IVW 2.3413 0.6733
Pleiotropy-test Intercept
−0.0089 0.7021

3.2 Impact of COVID-19 on male infertility

Genetic predisposition to COVID-19 infection was not found to be associated with the male infertility risk (IVW: OR = 0.7668, 95% CI = 0.3798–1.5484, p = 0.4590; Table 3). Similar null associations were also observed for COVID-19 severity phenotypes: for hospitalized COVID-19 patients: OR = 0.9085, 95% CI = 0.7100–1.1625, p = 0.4454; for cases of very severe respiratory-confirmed: OR = 0.9312, 95% CI = 0.7696–1.1267, p = 0.4633; and for patients with critical illness: OR = 0.94700, 95% CI = 0.8064–1.1121, p = 0.5063 (Table 5).

Table 5

MR estimates of the causal effect of COVID-19 phenotypes on the risk of male infertility

Outcome Method OR 95% CI p-value
COVID-19 IVW 0.7668 0.3798–1.5484 0.4590
MR Egger 0.0722 0.0078–0.6701 0.0687
Weighted median 0.8117 0.3487–1.8893 0.6284
Weighted mode 0.9141 0.3392–2.4635 0.8650
COVID-19 (hospitalized) IVW 0.9085 0.7100–1.1625 0.4454
MR Egger 0.9487 0.5423–1.6596 0.8624
Weighted median 0.9163 0.6854–1.2249 0.5549
Weighted mode 0.9311 0.6674–1.2991 0.6919
COVID-19 (very severe respiratory-confirmed) IVW 0.9312 0.7696–1.1267 0.4633
MR Egger 0.9860 0.6202–1.5675 0.9548
Weighted median 0.9442 0.7488–1.1905 0.6273
Weighted mode 0.9569 0.7200–1.2712 0.7716
COVID-19 (critical illness) IVW 0.94700 0.8064–1.1121 0.5063
MR Egger 0.9378 0.6457–1.3620 0.7580
Weighted median 0.9560 0.7890–1.1585 0.6462
Weighted mode 0.9702 0.7571–1.2432 0.8225

IVW, inverse variance weighted; MR, Mendelian randomization; OR: odds ratio; CI: confidence interval.

Sensitivity analyses and pleiotropy assessments (Cochran’s Q p > 0.05; MR-Egger intercept p > 0.05) further supported the robustness of these findings (Table 6 and Figure 4). Leave-one-out analysis revealed no influential SNPs (Figure S2).

Table 6

Sensitivity analyses for the MR of COVID-19 phenotypes on male infertility, including Cochran’s Q test for heterogeneity and the MR-Egger intercept test for pleiotropy

Exposure Q/intercept p-value
COVID-19
Cochran Q test Q
MR Egger 3.5089 0.6220
IVW 8.1699 0.2259
Pleiotropy test Intercept
0.2028 0.0833
COVID-19 (hospitalized)
Cochran Q test Q
MR Egger 1.3465 0.8534
IVW 1.3751 0.9270
Pleiotropy test Intercept
−0.0114 0.8740
COVID-19 (very severe respiratory confirmed)
Cochran Q test Q
MR Egger 1.3795 0.9266
IVW 1.4498 0.9628
Pleiotropy test Intercept
−0.0184 0.8013
COVID-19 (critical illness)
Cochran Q test Q
MR Egger 0.9590 0.8112
IVW 0.9622 0.9155
Figure 4 MR analysis of COVID-19 on male infertility. SNP, single-nucleotide polymorphisms; IVW, inverse variance weighted; MR, Mendelian randomization; OR: odds ratio; CI: confidence interval.
Figure 4

MR analysis of COVID-19 on male infertility. SNP, single-nucleotide polymorphisms; IVW, inverse variance weighted; MR, Mendelian randomization; OR: odds ratio; CI: confidence interval.

4 Discussion

COVID-19 can induce dysfunction across various organ systems. While the respiratory system is predominantly affected, extrapulmonary manifestations involving organs like the testes and placenta have been documented [25]. However, the causal relationship between COVID-19 and reproductive complications (e.g., spontaneous abortion and male infertility) remains ambiguous due to the potential confounding factors and the inherent limitations of observational studies. Our two-sample MR analysis investigated this potential causality and found no significant genetic evidence linking COVID-19 susceptibility or severity to increased risks of male infertility or spontaneous abortion.

Currently, the majority of studies examining the association between COVID-19 and male infertility focus on the impact of COVID-19 on sperm quality. Li et al. detected the presence of SARS-CoV-2 in 6 out of 38 semen samples, with 4 patients in the acute phase and 2 in the convalescent phase [5]. Holtmann et al. found that sperm concentration and motility were significantly lower in recovered patients who had experienced fever compared to those who had not [26]. This implies that fever and disease severity may influence semen quality and potentially establish a link between COVID-19 and altered sperm parameters [26]. A prospective study indicated that COVID-19 infection was associated with male seminal inflammation and impaired seminal quality in the early stages of the disease, but these changes were partially restored after 1–2 sperm generation cycles [27]. Although relevant studies have established a correlation between COVID-19 infection and decreased sperm quality, the long-term implications for male infertility remain unclear. A recent clinical study by Sarier et al. directly compared the spermiogram parameters of infertile men before and during the first year of the COVID-19 pandemic [28]. They observed no significant differences in semen volume, the rates of normospermia, or the distribution of various pathological spermiogram findings, such as oligoasthenoteratozoospermia and asthenoteratozoospermia, between the pre-pandemic and pandemic periods [28]. This clinical observation and our MR results consistently show no causal link between genetic susceptibility to COVID-19 and male infertility risk. Despite the pandemic, there was no significant population-level decline in semen parameters or rise in male infertility. This is likely due to: (1) subclinical, short-term changes in semen parameters that do not lead to infertility and (2) sperm quality normalizing within one spermatogenic cycle (∼74 days) post-infection [29], rendering transient effects negligible for long-term fertility in genetically predisposed men. Notably, the GWAS sample size for male infertility was relatively small (680 cases), limiting statistical power and potentially missing small effects, though no significant associations, heterogeneity, or pleiotropy were found. In contrast, the spontaneous abortion analysis included a much larger number of cases (9,113), providing stronger evidence to support the null findings.

Evidence on the causal relationship between COVID-19 and spontaneous abortion remains limited. Although one retrospective study noted a higher miscarriage incidence (10.2%) among infected women, regression analysis showed COVID-19 was not a reliable predictor of pregnancy loss [13]. Most studies of viral impact in pregnancy focus on later trimesters, and early guidance recommended postponing assisted reproduction due to theoretical risks [30,31,32,33]. However, our MR analysis found no significant causal link between COVID-19 and spontaneous abortion. This is supported by an independent two-sample MR study using UK Biobank data, which also found no causal effect of hospitalized COVID-19 on miscarriage [34]. Further reinforcing these findings, a large case–control study found no association between COVID-19 vaccination during pregnancy and spontaneous abortion risk, regardless of dose timing or manufacturer [35]. Collectively, these complementary lines of evidence provide consistent reassurance, indicating that neither contracting COVID-19 nor receiving the recommended COVID-19 vaccine poses an increased risk of spontaneous abortion. The null findings align with several biological realities. First, SARS-CoV-2 primarily employs angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) as cellular entry receptors through its surface spike protein [36]. However, the ACE2 and TMPRSS2 expression in the human placenta, particularly during the first trimester, is minimal or restricted to specific non-critical cell types. Moreover, their expression is notably absent or negligible in syncytiotrophoblasts, which mediate maternal-fetal exchange and barrier functions [37]. This spatially constrained and developmentally limited receptor expression drastically reduces the likelihood of placental SARS-CoV-2 infection and subsequent vertical transmission during early gestation. Second, first-trimester pregnancy loss is predominantly driven by embryonic chromosomal abnormalities (aneuploidy) [38,39]. While maternal infection can be a contributing factor in some cases, our genetic findings do not support SARS-CoV-2 as a major causative agent. Furthermore, an important avenue for future research will be to investigate the potential joint impact of dual parental COVID-19 infection (both maternal and paternal) around the time of conception on early pregnancy outcomes, which was beyond the scope of this study. This comprehensive understanding is crucial for alleviating public anxiety, particularly among pregnant women who are concerned about early pregnancy loss. It also serves as a solid foundation for supporting evidence-based public health recommendations regarding both infection prevention and management during the ongoing pandemic.

This study has several limitations that warrant consideration. First, residual bias from weak instruments or undetected horizontal pleiotropy, inherent to MR, cannot be fully ruled out despite robust sensitivity analyses. Second, our findings are based on European-ancestry GWAS data, limiting their generalizability to other populations. Third, our analysis did not differentiate between SARS-CoV-2 variants, which may have differing pathogenic effects. Fourth, the statistical power for the male infertility analysis was limited by a relatively small case number (n = 680), potentially obscuring subtle causal effects. Future studies incorporating diverse populations, larger male infertility cohorts, and variant-specific data are warranted to further elucidate the long-term reproductive implications of SARS-CoV-2 infection.

In conclusion, our MR study provides robust genetic evidence against a causal relationship between COVID-19 and an increased risk of male infertility or spontaneous abortion. These findings have key clinical implications. Clinicians can reassure convalescent men that any infection-related semen alterations are likely transient and reassure pregnant women that a first-trimester COVID-19 infection is not a direct indication for termination. Clinical management should be guided by standard obstetric and urological indications not solely by COVID-19 infection status.

# Yufeng Liang and Xueshan Ma are both first authors.

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  1. Funding information: This work was supported by grants from Shandong Provincial Natural Science Foundation (Nos. ZR2020QC102); Technology Development Plan of Tai’an City (Nos. 2019NS237, 2022NS275, and 2020NS221); Medical and Health Science and Technology Development Plan in Shandong Province (No. 2019WS209); and Taian Science and Technology Innovation Development Project (Policy Guidance Category) No.: 2023NS256.

  2. Author contributions: Conception and methodology, Yufeng Liang and Xueshan Ma; investigation and formal analysis, Chunli Liu and Xiuqing He; writing – original draft, Yufeng Liang and Xueshan Ma; writing – review and editing, Tao Liu and Xiaoming Niu. All authors read and approved the final manuscript.

  3. Conflict of interest: Authors state no conflict of interest.

  4. Data availability statement: The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Received: 2025-03-13
Revised: 2025-08-20
Accepted: 2025-09-08
Published Online: 2025-10-30

© 2025 the author(s), published by De Gruyter

This work is licensed under the Creative Commons Attribution 4.0 International License.

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https://doi.org/10.1515/biol-2025-1188
Keywords for this article
COVID-19; Mendelian randomization; spontaneous abortion; male infertility; causal relationship
Creative Commons
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Articles in the same Issue

  1. Heat stroke associated with novel leukaemia inhibitory factor receptor gene variant in a Chinese infant
  2. PSME2 exacerbates ulcerative colitis by disrupting intestinal barrier function and promoting autophagy-dependent inflammation
  3. Can coronavirus disease 2019 affect male fertility or cause spontaneous abortion? A two-sample Mendelian randomization analysis
  4. Biomedical Sciences
  5. Mechanism of triptolide regulating proliferation and apoptosis of hepatoma cells by inhibiting JAK/STAT pathway
  6. Maslinic acid improves mitochondrial function and inhibits oxidative stress and autophagy in human gastric smooth muscle cells
  7. Comparative analysis of inflammatory biomarkers for the diagnosis of neonatal sepsis: IL-6, IL-8, SAA, CRP, and PCT
  8. Post-pandemic insights on COVID-19 and premature ovarian insufficiency
  9. Proteome differences of dental stem cells between permanent and deciduous teeth by data-independent acquisition proteomics
  10. Optimizing a modified cetyltrimethylammonium bromide protocol for fungal DNA extraction: Insights from multilocus gene amplification
  11. Preliminary analysis of the role of small hepatitis B surface proteins mutations in the pathogenesis of occult hepatitis B infection via the endoplasmic reticulum stress-induced UPR-ERAD pathway
  12. Efficacy of alginate-coated gold nanoparticles against antibiotics-resistant Staphylococcus and Streptococcus pathogens of acne origins
  13. Battling COVID-19 leveraging nanobiotechnology: Gold and silver nanoparticle–B-escin conjugates as SARS-CoV-2 inhibitors
  14. Neurodegenerative diseases and neuroinflammation-induced apoptosis
  15. Impact of fracture fixation surgery on cognitive function and the gut microbiota in mice with a history of stroke
  16. COLEC10: A potential tumor suppressor and prognostic biomarker in hepatocellular carcinoma through modulation of EMT and PI3K-AKT pathways
  17. High-temperature requirement serine protease A2 inhibitor UCF-101 ameliorates damaged neurons in traumatic brain-injured rats by the AMPK/NF-κB pathway
  18. SIK1 inhibits IL-1β-stimulated cartilage apoptosis and inflammation in vitro through the CRTC2/CREB1 signaling
  19. Rutin–chitooligosaccharide complex: Comprehensive evaluation of its anti-inflammatory and analgesic properties in vitro and in vivo
  20. Knockdown of Aurora kinase B alleviates high glucose-triggered trophoblast cells damage and inflammation during gestational diabetes
  21. Calcium-sensing receptors promoted Homer1 expression and osteogenic differentiation in bone marrow mesenchymal stem cells
  22. ABI3BP can inhibit the proliferation, invasion, and epithelial–mesenchymal transition of non-small-cell lung cancer cells
  23. Changes in blood glucose and metabolism in hyperuricemia mice
  24. Rapid detection of the GJB2 c.235delC mutation based on CRISPR-Cas13a combined with lateral flow dipstick
  25. IL-11 promotes Ang II-induced autophagy inhibition and mitochondrial dysfunction in atrial fibroblasts
  26. Short-chain fatty acid attenuates intestinal inflammation by regulation of gut microbial composition in antibiotic-associated diarrhea
  27. Application of metagenomic next-generation sequencing in the diagnosis of pathogens in patients with diabetes complicated by community-acquired pneumonia
  28. NAT10 promotes radiotherapy resistance in non-small cell lung cancer by regulating KPNB1-mediated PD-L1 nuclear translocation
  29. Phytol-mixed micelles alleviate dexamethasone-induced osteoporosis in zebrafish: Activation of the MMP3–OPN–MAPK pathway-mediating bone remodeling
  30. Association between TGF-β1 and β-catenin expression in the vaginal wall of patients with pelvic organ prolapse
  31. Primary pleomorphic liposarcoma involving bilateral ovaries: Case report and literature review
  32. Effects of de novo donor-specific Class I and II antibodies on graft outcomes after liver transplantation: A pilot cohort study
  33. Sleep architecture in Alzheimer’s disease continuum: The deep sleep question
  34. Ephedra fragilis plant extract: A groundbreaking corrosion inhibitor for mild steel in acidic environments – electrochemical, EDX, DFT, and Monte Carlo studies
  35. Langerhans cell histiocytosis in an adult patient with upper jaw and pulmonary involvement: A case report
  36. Inhibition of mast cell activation by Jaranol-targeted Pirin ameliorates allergic responses in mouse allergic rhinitis
  37. Aeromonas veronii-induced septic arthritis of the hip in a child with acute lymphoblastic leukemia
  38. Clusterin activates the heat shock response via the PI3K/Akt pathway to protect cardiomyocytes from high-temperature-induced apoptosis
  39. Research progress on fecal microbiota transplantation in tumor prevention and treatment
  40. Low-pressure exposure influences the development of HAPE
  41. Stigmasterol alleviates endplate chondrocyte degeneration through inducing mitophagy by enhancing PINK1 mRNA acetylation via the ESR1/NAT10 axis
  42. AKAP12, mediated by transcription factor 21, inhibits cell proliferation, metastasis, and glycolysis in lung squamous cell carcinoma
  43. Association between PAX9 or MSX1 gene polymorphism and tooth agenesis risk: A meta-analysis
  44. A case of bloodstream infection caused by Neisseria gonorrhoeae
  45. Case of nasopharyngeal tuberculosis complicated with cervical lymph node and pulmonary tuberculosis
  46. p-Cymene inhibits pro-fibrotic and inflammatory mediators to prevent hepatic dysfunction
  47. GFPT2 promotes paclitaxel resistance in epithelial ovarian cancer cells via activating NF-κB signaling pathway
  48. Transfer RNA-derived fragment tRF-36 modulates varicose vein progression via human vascular smooth muscle cell Notch signaling
  49. RTA-408 attenuates the hepatic ischemia reperfusion injury in mice possibly by activating the Nrf2/HO-1 signaling pathway
  50. Decreased serum TIMP4 levels in patients with rheumatoid arthritis
  51. Sirt1 protects lupus nephritis by inhibiting the NLRP3 signaling pathway in human glomerular mesangial cells
  52. Sodium butyrate aids brain injury repair in neonatal rats
  53. Interaction of MTHFR polymorphism with PAX1 methylation in cervical cancer
  54. Convallatoxin inhibits proliferation and angiogenesis of glioma cells via regulating JAK/STAT3 pathway
  55. The effect of the PKR inhibitor, 2-aminopurine, on the replication of influenza A virus, and segment 8 mRNA splicing
  56. Effects of Ire1 gene on virulence and pathogenicity of Candida albicans
  57. Small cell lung cancer with small intestinal metastasis: Case report and literature review
  58. GRB14: A prognostic biomarker driving tumor progression in gastric cancer through the PI3K/AKT signaling pathway by interacting with COBLL1
  59. 15-Lipoxygenase-2 deficiency induces foam cell formation that can be restored by salidroside through the inhibition of arachidonic acid effects
  60. FTO alleviated the diabetic nephropathy progression by regulating the N6-methyladenosine levels of DACT1
  61. Clinical relevance of inflammatory markers in the evaluation of severity of ulcerative colitis: A retrospective study
  62. Zinc valproic acid complex promotes osteoblast differentiation and exhibits anti-osteoporotic potential
  63. Primary pulmonary synovial sarcoma in the bronchial cavity: A case report
  64. Metagenomic next-generation sequencing of alveolar lavage fluid improves the detection of pulmonary infection
  65. Uterine tumor resembling ovarian sex cord tumor with extensive rhabdoid differentiation: A case report
  66. Genomic analysis of a novel ST11(PR34365) Clostridioides difficile strain isolated from the human fecal of a CDI patient in Guizhou, China
  67. Effects of tiered cardiac rehabilitation on CRP, TNF-α, and physical endurance in older adults with coronary heart disease
  68. Changes in T-lymphocyte subpopulations in patients with colorectal cancer before and after acupoint catgut embedding acupuncture observation
  69. Modulating the tumor microenvironment: The role of traditional Chinese medicine in improving lung cancer treatment
  70. Alterations of metabolites related to microbiota–gut–brain axis in plasma of colon cancer, esophageal cancer, stomach cancer, and lung cancer patients
  71. Research on individualized drug sensitivity detection technology based on bio-3D printing technology for precision treatment of gastrointestinal stromal tumors
  72. CEBPB promotes ulcerative colitis-associated colorectal cancer by stimulating tumor growth and activating the NF-κB/STAT3 signaling pathway
  73. Oncolytic bacteria: A revolutionary approach to cancer therapy
  74. A de novo meningioma with rapid growth: A possible malignancy imposter?
  75. Diagnosis of secondary tuberculosis infection in an asymptomatic elderly with cancer using next-generation sequencing: Case report
  76. Hesperidin and its zinc(ii) complex enhance osteoblast differentiation and bone formation: In vitro and in vivo evaluations
  77. Research progress on the regulation of autophagy in cardiovascular diseases by chemokines
  78. Anti-arthritic, immunomodulatory, and inflammatory regulation by the benzimidazole derivative BMZ-AD: Insights from an FCA-induced rat model
  79. Immunoassay for pyruvate kinase M1/2 as an Alzheimer’s biomarker in CSF
  80. The role of HDAC11 in age-related hearing loss: Mechanisms and therapeutic implications
  81. Evaluation and application analysis of animal models of PIPNP based on data mining
  82. Therapeutic approaches for liver fibrosis/cirrhosis by targeting pyroptosis
  83. Fabrication of zinc oxide nanoparticles using Ruellia tuberosa leaf extract induces apoptosis through P53 and STAT3 signalling pathways in prostate cancer cells
  84. Haplo-hematopoietic stem cell transplantation and immunoradiotherapy for severe aplastic anemia complicated with nasopharyngeal carcinoma: A case report
  85. Modulation of the KEAP1-NRF2 pathway by Erianin: A novel approach to reduce psoriasiform inflammation and inflammatory signaling
  86. The expression of epidermal growth factor receptor 2 and its relationship with tumor-infiltrating lymphocytes and clinical pathological features in breast cancer patients
  87. Innovations in MALDI-TOF Mass Spectrometry: Bridging modern diagnostics and historical insights
  88. BAP1 complexes with YY1 and RBBP7 and its downstream targets in ccRCC cells
  89. Hypereosinophilic syndrome with elevated IgG4 and T-cell clonality: A report of two cases
  90. Electroacupuncture alleviates sciatic nerve injury in sciatica rats by regulating BDNF and NGF levels, myelin sheath degradation, and autophagy
  91. Polydatin prevents cholesterol gallstone formation by regulating cholesterol metabolism via PPAR-γ signaling
  92. RNF144A and RNF144B: Important molecules for health
  93. Analysis of the detection rate and related factors of thyroid nodules in the healthy population
  94. Artesunate inhibits hepatocellular carcinoma cell migration and invasion through OGA-mediated O-GlcNAcylation of ZEB1
  95. Endovascular management of post-pancreatectomy hemorrhage caused by a hepatic artery pseudoaneurysm: Case report and review of the literature
  96. Efficacy and safety of anti-PD-1/PD-L1 antibodies in patients with relapsed refractory diffuse large B-cell lymphoma: A meta-analysis
  97. SATB2 promotes humeral fracture healing in rats by activating the PI3K/AKT pathway
  98. Overexpression of the ferroptosis-related gene, NFS1, corresponds to gastric cancer growth and tumor immune infiltration
  99. Understanding risk factors and prognosis in diabetic foot ulcers
  100. Atractylenolide I alleviates the experimental allergic response in mice by suppressing TLR4/NF-kB/NLRP3 signalling
  101. FBXO31 inhibits the stemness characteristics of CD147 (+) melanoma stem cells
  102. Immune molecule diagnostics in colorectal cancer: CCL2 and CXCL11
  103. Inhibiting CXCR6 promotes senescence of activated hepatic stellate cells with limited proinflammatory SASP to attenuate hepatic fibrosis
  104. Cadmium toxicity, health risk and its remediation using low-cost biochar adsorbents
  105. Pulmonary cryptococcosis with headache as the first presentation: A case report
  106. Solitary pulmonary metastasis with cystic airspaces in colon cancer: A rare case report
  107. RUNX1 promotes denervation-induced muscle atrophy by activating the JUNB/NF-κB pathway and driving M1 macrophage polarization
  108. Morphometric analysis and immunobiological investigation of Indigofera oblongifolia on the infected lung with Plasmodium chabaudi
  109. The NuA4/TIP60 histone-modifying complex and Hr78 modulate the Lobe2 mutant eye phenotype
  110. Experimental study on salmon demineralized bone matrix loaded with recombinant human bone morphogenetic protein-2: In vitro and in vivo study
  111. A case of IgA nephropathy treated with a combination of telitacicept and half-dose glucocorticoids
  112. Analgesic and toxicological evaluation of cannabidiol-rich Moroccan Cannabis sativa L. (Khardala variety) extract: Evidence from an in vivo and in silico study
  113. Wound healing and signaling pathways
  114. Combination of immunotherapy and whole-brain radiotherapy on prognosis of patients with multiple brain metastases: A retrospective cohort study
  115. To explore the relationship between endometrial hyperemia and polycystic ovary syndrome
  116. Research progress on the impact of curcumin on immune responses in breast cancer
  117. Biogenic Cu/Ni nanotherapeutics from Descurainia sophia (L.) Webb ex Prantl seeds for the treatment of lung cancer
  118. Dapagliflozin attenuates atrial fibrosis via the HMGB1/RAGE pathway in atrial fibrillation rats
  119. Glycitein alleviates inflammation and apoptosis in keratinocytes via ROS-associated PI3K–Akt signalling pathway
  120. ADH5 inhibits proliferation but promotes EMT in non-small cell lung cancer cell through activating Smad2/Smad3
  121. Apoptotic efficacies of AgNPs formulated by Syzygium aromaticum leaf extract on 32D-FLT3-ITD human leukemia cell line with PI3K/AKT/mTOR signaling pathway
  122. Novel cuproptosis-related genes C1QBP and PFKP identified as prognostic and therapeutic targets in lung adenocarcinoma
  123. Bee venom promotes exosome secretion and alters miRNA cargo in T cells
  124. Treatment of pure red cell aplasia in a chronic kidney disease patient with roxadustat: A case report
  125. Comparative bioinformatics analysis of the Wnt pathway in breast cancer: Selection of novel biomarker panels associated with ER status
  126. Kynurenine facilitates renal cell carcinoma progression by suppressing M2 macrophage pyroptosis through inhibition of CASP1 cleavage
  127. RFX5 promotes the growth, motility, and inhibits apoptosis of gastric adenocarcinoma cells through the SIRT1/AMPK axis
  128. ALKBH5 exacerbates early cardiac damage after radiotherapy for breast cancer via m6A demethylation of TLR4
  129. Phytochemicals of Roman chamomile: Antioxidant, anti-aging, and whitening activities of distillation residues
  130. Circadian gene Cry1 inhibits the tumorigenicity of hepatocellular carcinoma by the BAX/BCL2-mediated apoptosis pathway
  131. The TNFR-RIPK1/RIPK3 signalling pathway mediates the effect of lanthanum on necroptosis of nerve cells
  132. Longitudinal monitoring of autoantibody dynamics in patients with early-stage non-small-cell lung cancer undergoing surgery
  133. The potential role of rutin, a flavonoid, in the management of cancer through modulation of cell signaling pathways
  134. Construction of pectinase gene engineering microbe and its application in tobacco sheets
  135. Construction of a microbial abundance prognostic scoring model based on intratumoral microbial data for predicting the prognosis of lung squamous cell carcinoma
  136. Sepsis complicated by haemophagocytic lymphohistiocytosis triggered by methicillin-resistant Staphylococcus aureus and human herpesvirus 8 in an immunocompromised elderly patient: A case report
  137. Sarcopenia in liver transplantation: A comprehensive bibliometric study of current research trends and future directions
  138. Advances in cancer immunotherapy and future directions in personalized medicine
  139. Ecology and Environmental Science
  140. Optimization and comparative study of Bacillus consortia for cellulolytic potential and cellulase enzyme activity
  141. The complete mitochondrial genome analysis of Haemaphysalis hystricis Supino, 1897 (Ixodida: Ixodidae) and its phylogenetic implications
  142. Epidemiological characteristics and risk factors analysis of multidrug-resistant tuberculosis among tuberculosis population in Huzhou City, Eastern China
  143. Indices of human impacts on landscapes: How do they reflect the proportions of natural habitats?
  144. Genetic analysis of the Siberian flying squirrel population in the northern Changbai Mountains, Northeast China: Insights into population status and conservation
  145. Diversity and environmental drivers of Suillus communities in Pinus sylvestris var. mongolica forests of Inner Mongolia
  146. Global assessment of the fate of nitrogen deposition in forest ecosystems: Insights from 15N tracer studies
  147. Fungal and bacterial pathogenic co-infections mainly lead to the assembly of microbial community in tobacco stems
  148. Influencing of coal industry related airborne particulate matter on ocular surface tear film injury and inflammatory factor expression in Sprague-Dawley rats
  149. Temperature-dependent development, predation, and life table of Sphaerophoria macrogaster (Thomson) (Diptera: Syrphidae) feeding on Myzus persicae (Sulzer) (Homoptera: Aphididae)
  150. Agriculture
  151. Integrated analysis of transcriptome, sRNAome, and degradome involved in the drought-response of maize Zhengdan958
  152. Variation in flower frost tolerance among seven apple cultivars and transcriptome response patterns in two contrastingly frost-tolerant selected cultivars
  153. Heritability of durable resistance to stripe rust in bread wheat (Triticum aestivum L.)
  154. Molecular mechanism of follicular development in laying hens based on the regulation of water metabolism
  155. Animal Science
  156. Effect of sex ratio on the life history traits of an important invasive species, Spodoptera frugiperda
  157. Plant Sciences
  158. Hairpin in a haystack: In silico identification and characterization of plant-conserved microRNA in Rafflesiaceae
  159. Widely targeted metabolomics of different tissues in Rubus corchorifolius
  160. The complete chloroplast genome of Gerbera piloselloides (L.) Cass., 1820 (Carduoideae, Asteraceae) and its phylogenetic analysis
  161. Field trial to correlate mineral solubilization activity of Pseudomonas aeruginosa and biochemical content of groundnut plants
  162. Correlation analysis between semen routine parameters and sperm DNA fragmentation index in patients with semen non-liquefaction: A retrospective study
  163. Plasticity of the anatomical traits of Rhododendron L. (Ericaceae) leaves and its implications in adaptation to the plateau environment
  164. Effects of Piriformospora indica and arbuscular mycorrhizal fungus on growth and physiology of Moringa oleifera under low-temperature stress
  165. Effects of different sources of potassium fertiliser on yield, fruit quality and nutrient absorption in “Harward” kiwifruit (Actinidia deliciosa)
  166. Comparative efficiency and residue levels of spraying programs against powdery mildew in grape varieties
  167. The DREB7 transcription factor enhances salt tolerance in soybean plants under salt stress
  168. Using plant electrical signals of water hyacinth (Eichhornia crassipes) for water pollution monitoring
  169. Food Science
  170. Phytochemical analysis of Stachys iva: Discovering the optimal extract conditions and its bioactive compounds
  171. Review on role of honey in disease prevention and treatment through modulation of biological activities
  172. Computational analysis of polymorphic residues in maltose and maltotriose transporters of a wild Saccharomyces cerevisiae strain
  173. Optimization of phenolic compound extraction from Tunisian squash by-products: A sustainable approach for antioxidant and antibacterial applications
  174. Liupao tea aqueous extract alleviates dextran sulfate sodium-induced ulcerative colitis in rats by modulating the gut microbiota
  175. Toxicological qualities and detoxification trends of fruit by-products for valorization: A review
  176. Polyphenolic spectrum of cornelian cherry fruits and their health-promoting effect
  177. Optimizing the encapsulation of the refined extract of squash peels for functional food applications: A sustainable approach to reduce food waste
  178. Advancements in curcuminoid formulations: An update on bioavailability enhancement strategies curcuminoid bioavailability and formulations
  179. Impact of saline sprouting on antioxidant properties and bioactive compounds in chia seeds
  180. The dilemma of food genetics and improvement
  181. Bioengineering and Biotechnology
  182. Impact of hyaluronic acid-modified hafnium metalorganic frameworks containing rhynchophylline on Alzheimer’s disease
  183. Emerging patterns in nanoparticle-based therapeutic approaches for rheumatoid arthritis: A comprehensive bibliometric and visual analysis spanning two decades
  184. Application of CRISPR/Cas gene editing for infectious disease control in poultry
  185. Preparation of hafnium nitride-coated titanium implants by magnetron sputtering technology and evaluation of their antibacterial properties and biocompatibility
  186. Preparation and characterization of lemongrass oil nanoemulsion: Antimicrobial, antibiofilm, antioxidant, and anticancer activities
  187. Corrigendum
  188. Corrigendum to “Utilization of convolutional neural networks to analyze microscopic images for high-throughput screening of mesenchymal stem cells”
  189. Corrigendum to “Effects of Ire1 gene on virulence and pathogenicity of Candida albicans”
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