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Article

Serum Bilirubin and Sperm Quality in Adult Population

by
Yuan-Yuei Chen
1,2 and
Wei-Liang Chen
3,4,5,*
1
Department of Pathology, Tri-Service General Hospital, School of Medicine, National Defense Medical Center, Taipei 114, Taiwan
2
Department of Pathology, Tri-Service General Hospital Songshan Branch, School of Medicine, National Defense Medical Center, Taipei 114,Taiwan
3
Division of Family Medicine, Department of Family and Community Medicine, Tri-Service General Hospital, School of Medicine, National Defense Medical Center, Taipei 114, Taiwan
4
Division of Geriatric Medicine, Department of Family and Community Medicine, Tri-Service General Hospital, School of Medicine, National Defense Medical Center, Taipei 114, Taiwan
5
Department of Biochemistry, National Defense Medical Center, Taipei,114, Taiwan
*
Author to whom correspondence should be addressed.
Toxics 2022, 10(6), 295; https://doi.org/10.3390/toxics10060295
Submission received: 18 April 2022 / Revised: 20 May 2022 / Accepted: 26 May 2022 / Published: 30 May 2022
(This article belongs to the Section Toxicology)
Review Reports Versions Notes

Abstract

:
The neurotoxicity of bilirubin has been extensively reported in numerous studies. However, the association between bilirubin and male fertility has not yet been studied. The main goal of this study was to investigate the association between serum total bilirubin and sperm quality in an adult population. In this cross-sectional study, 9057 participants who attended the MJ health examination (2010–2016) were enrolled. Sperm specimens were collected by masturbation, and sperm quality was analyzed in accordance with the WHO criteria. Serum total bilirubin levels were measured by an automatic biochemical profile analyzer. Thereafter, the associations between serum total bilirubin and sperm quality were determined by a multivariable linear regression. Serum total bilirubin was inversely associated with sperm concentration and normal morphology with β values of −13.82 (95% CI: −26.99, −0.64) and −18.38 (95% CI: −30.46, −6.29) after adjusting for covariables. The highest levels of serum total bilirubin were significantly associated with sperm concentration and normal morphology with β values of −14.15 (95% CI: −28.36, 0.06) and −21.15 (95% CI: −33.99, −8.30). Our study highlighted the potential impact of serum bilirubin on sperm quality in a male population. Additional longitudinal research is necessary to explore these findings and underlying mechanisms.

1. Introduction

Bilirubin, a tetrapyrrolic pigment and albumin-bound reversible compound, is found in plasma [1]. It is a derivative of heme catabolism, which is released by hemoglobin and cytochromes [2]. Serum bilirubin levels represent the condition of the heme turnover rate, canalicular excretion, and hepatic uptake and conjugation [3]. Numerous studies have reported that hyperbilirubinemia may potentially lead to irreversible neurological damage by accumulating bilirubin in the central nervous system [4,5,6]. Unbound bilirubin induces a variety of cellular and molecular events that result in neurotoxicity [7,8].
Mounting studies have indicated that decreasing sperm quality is associated with multiple systemic diseases. Emerging evidence has reported that obesity negatively impacts male fertility and directly changes sperm function and molecular composition [9,10,11]. Metabolic syndrome, a cluster of medical conditions characterized by abdominal obesity, dyslipidemia, hypertension, and high fasting glucose, is suggested to be associated with alteration of spermatogenesis [12,13]. Reduced levels of serum testosterone and sperm quality have been found in patients with nonalcoholic fatty liver disease (NAFLD) [14]. However, the relationship between bilirubin and male reproductive function has not yet been examined. The goal of the current study was to investigate the relationship between serum total bilirubin and sperm quality in an adult population from Taiwan.

2. Methods

2.1. Study Design and Participants

The MJ Health Center is a membership-oriented private institute with four health check-up clinics in Taiwan, the MJ Health Management Institution. The center provides periodic health examinations to its members. A series of tests such as blood, urine, anthropometric measurements, physical examination, and medical history are included in this large health research database.
In this study, we excluded those who had missing data on serum total bilirubin, sperm quality analysis, and demographic characteristic data. A total of 9057 eligible participants who attended one or more health examinations from 2010 to 2016 were included in the analysis. Personal identifiers were removed when data were released for the research. Informed consent documents were provided for participants to sign and let them make the decision to volunteer for the study. Ethics approval was approved by the Institutional Review Board (IRB) of the Tri-Service General Hospital and the MJ Health Management Institution.

2.2. Sperm Quality Analysis

Participants contributed their semen samples by masturbation after they had abstained for at least 3 days. Samples were stored in sterile containers that liquefied at 37 °C for 20 min and were sent to the laboratory for analysis [15]. Four parameters of sperm quality, including sperm concentration, total motility, progressive motility, and normal morphology, were recorded. A microcell counting chamber and a phase contrast microscope were used to assess sperm concentration. Sperm motility was classified as total motility and progressive motility based on the WHO 2010 classification [16]. Two hundred sperm cells were categorized into four different grades: A, B, C, or D. Total motility was defined as A + B + C and progressive motility as A + B. According to the WHO criteria in 2010, a normal sample was defined as if 4% (or 5th centile) or more of the observed sperm has normal sperm morphology.

2.3. Serum Total Bilirubin Measurement

The levels of serum total bilirubin were measured by a timed end-point Diazo method, using automatic biochemistry profiling (Beckman Synchron LX20 Beckman Coulter Inc., Fullerton, CA, USA). The analytical range and the reference range are 0.1~30 mg/dL and 0.2 to 1.3 mg/dL, respectively.

2.4. Covariates

A history of hypertension (HTN) and type II diabetes mellitus (DM) was obtained from a self-reported questionnaire. A question “How many packs do you smoke per day?” was used to determine the cigarette smoking status of participants. Systolic blood pressure (SBP) was measured by a standard sphygmomanometer when the subjects sat down. To collect the blood samples for analyzing laboratory data, including fasting plasma glucose (FPG), aspartate aminotransferase (AST), total cholesterol (CHO), and C-reactive protein (CRP), participants had to fast for at least 8 h, and these samples were measured by standard procedures.

2.5. Statistical Analyses

Associations between serum total bilirubin and sperm quality were performed using multivariable linear regression. The associations between various quartiles and the presence of sperm quality were analyzed by logistic regression. These regressions were adjusted by multivariable models, as follows. Model 1 was unadjusted. Model 2 included Model 1 and age. Model 3 included Model 2, ALT, Cr, and CRP. Model 4 included Model 3, a history of HTN, DM, and cigarette smoking. A significant difference was defined as a p-value of ≤0.05. Analyses in the current study were conducted using the Statistical Package for the Social Sciences, version 18.0 (SPSS Inc., Chicago, IL, USA) for Windows.

3. Results

3.1. Characteristics of Participants in Serum Total Bilirubin Quartiles

The general characteristic information of the 9057 subjects is listed in Table 1. The mean age of these quartiles was Q1: 32.33 ± 4.67, Q2: 32.35 ± 4.89, Q3: 32.01 ± 4.55, and Q4: 32.01 ± 4.79 years. The concentrations of serum total bilirubin of these quartile groups were 0.56 ± 0.10, 0.79 ± 0.06, 1.01 ± 0.07, and 1.50 ± 0.38, respectively. Participants in the highest quartile had significantly lower levels of FPG, CHO, and CRP and higher prevalence of cigarette smoking (p < 0.05). Sperm parameters, such as sperm concentration, motility, progressive motility, and normal morphology, showed significant differences across these quartiles (p < 0.05).

3.2. Associations between Serum Total Bilirubin and Sperm Quality

Associations between serum total bilirubin and sperm quality are shown in Table 2. Serum total bilirubin was significantly associated with decreased sperm motility and sperm normal morphology with β of −13.82 (95%CI: −26.99, −0.64) and −18.38 (95%CI: −30.46, −6.29). However, no significant difference was noted in the other sperm quality parameters.

3.3. Associations between Serum Total Bilirubin Quartiles and Sperm Quality

In Table 3, we divided serum total bilirubin into quartiles and analyzed the associations between these quartiles and sperm quality. The highest quartile of serum total bilirubin was inversely associated with sperm motility and sperm normal morphology with a β of −14.15 (95%CI: −28.36, 0.06) and −21.15 (95%CI: −33.99, −8.30).

4. Discussion

In this study, we highlighted the relationship between serum total bilirubin and sperm quality in a cross-sectional study. Serum total bilirubin had an inverse association with sperm motility and normal morphology. The highest quartile of serum total bilirubin was associated with decreased sperm motility and normal morphology. To the best of our knowledge, our study is the first to examine the association between serum total bilirubin and sperm quality in a reproductive-age male adult population.
The impacts of unconjugated bilirubin (UCB) on neurotoxicity have been broadly studied, and impairment of the cell membrane function, structure, and property are involved [17,18]. Generally, bilirubin is amphipathic but is lipophilic to cell membranes [19,20]. Apparently, it is possible that bilirubin can cross the blood–brain barrier (BBB) and enter the brain [21]. Bilirubin toxicity to brain cells might involve several plausible features, including induction of cell death, production of oxidative stress, and pro-inflammatory cytokines [22,23,24]. In a review study, Brito et al. reported that UCB affected brain microvascular endothelial cells, which play important roles in the maintenance of a functional BBB, and then caused hyperbilirubinemia-induced brain damage [25]. The interaction between bilirubin and spermatogenesis has not yet been reported in previous studies. The blood-testis barrier (BTB) might be the plausible target that explains how serum total bilirubin impacts sperm quality. Germ cell development is related to BTB because Sertoli cells can influence the chemical composition of the luminal fluid by controlling the adluminal compartment [26]. BTB also prevents germ cells from blood-borne noxious agents and inhibits cytotoxic agents into the seminiferous tubules [27]. Collectively, this barrier is the first line to protect the reproductive circulation system from toxic molecules. It is possible that bilirubin might lead to altered sperm quality by affecting BTB through several pathways.
The protective function of efflux transporters of Sertoli cells has been reported to prevent germ cells from toxic exposure [28,29]. Multidrug resistance-related protein (MRP), an efflux transporter that is detected mostly in Sertoli cells and Leydig cells of humans and mice [30,31], is known to transport a wide range of hydrophilic anion conjugates, hydrophobic xenobiotics, and natural compounds [32]. In a systemic review, MRP is suggested to be an important transporter of bilirubin that mediates ATP-dependent cellular export of bilirubin and has a protective effect against bilirubin-induced cytotoxicity [33]. The impact of bilirubin on spermatogenesis might be through this pathway.
Breast cancer resistance protein (BCRP) is an important efflux transporter that limits substances in the brain [34,35]. Xu et al. demonstrated that UCB elevation impaired the expression of BCRP at the BBB, which led to hepatic encephalopathy in vivo [36]. BCRP was observed in Sertoli cells, which was consistent with its localization at the BTB [37]. Organic anion-transporting polypeptides (OATPs) are influx pumps for a wild range of endogenous xenobiotics and compounds [38]. Steeg et al. indicated that OATP transporters played a crucial role in the uptake of unconjugated bile acids and drugs and hepatic reuptake of conjugated bilirubin [39]. Previous studies have reported that some of these uptake transporters are expressed only by spermatogonia, Sertoli cells, and BTB [40,41]. These membrane transporters might explain the impact of bilirubin on impaired sperm quality.
There are still several limitations to the present study. First, the cross-sectional design does not permit causal inference of the relationship between serum total bilirubin and sperm quality. A cohort analysis is needed in further studies. Second, we excluded individuals who might lead to selection bias and unsatisfactory generalization to avoid the confounding effects of hepatobiliary disease and to minimize age misclassification. Third, only one semen measurement was conducted for most participants, which limited us from having a repeated measurement, which might lead to within-person variations over time. Next, information on the participants’ medical history associated with bilirubin metabolism, such as hepatitis and bile duct obstruction, was lacking from the database. Last, laboratory data about potential confounding biomarkers, such as direct and indirect bilirubin, were not available from the MJ dataset. These biomarkers may be involved in the relationship between serum bilirubin and sperm quality by different mechanisms.

5. Conclusions

In this cross-sectional study, we highlighted that serum total bilirubin was negatively associated with sperm motility and normal morphology in an adult population. Although the causality of serum bilirubin to sperm quality must be established in a further prospective study, our finding provides epidemiological evidence for plausible interventional strategies for developing public health messages for men considering fatherhood.

Author Contributions

Conceptualization, Y.-Y.C. and W.-L.C.; methodology, Y.-Y.C. and W.-L.C.; software, Y.-Y.C. and W.-L.C.; validation, Y.-Y.C. and W.-L.C.; formal analysis, Y.-Y.C. and W.-L.C.; investigation, Y.-Y.C. and W.-L.C.; resources, Y.-Y.C. and W.-L.C.; data curation, Y.-Y.C. and W.-L.C.; writing—original draft preparation, Y.-Y.C.; writing—review and editing, W.-L.C.; visualization, Y.-Y.C. and W.-L.C.; supervision, W.-L.C. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Institutional Review Board Statement

The study was conducted in accordance with the Declaration of Helsinki, and approved by the Institutional Review Board of the Tri-Service General Hospital and the MJ Health Management Institution.

Informed Consent Statement

Informed consent was obtained from all subjects involved in the study.

Data Availability Statement

The datasets analyzed during the current study are not publicly available due to but are available from the corresponding author on reasonable request.

Conflicts of Interest

The authors declare no conflict of interest.

References

  1. Jacobsen, J.; Brodersen, R. Albumin-bilirubin binding mechanism. J. Biol. Chem. 1983, 258, 6319–6326. [Google Scholar] [CrossRef]
  2. Levitt, D.; Levitt, M. Quantitative assessment of the multiple processes responsible for bilirubin homeostasis in health and disease. Clin. Exp. Gastroenterol. 2014, 7, 307–328. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  3. Sticova, E.; Jirsa, M. New insights in bilirubin metabolism and their clinical implications. World J. Gastroenterol. 2013, 19, 6398–6407. [Google Scholar] [CrossRef] [PubMed]
  4. Watchko, J.F.; Tiribelli, C. Bilirubin-Induced Neurologic Damage—Mechanisms and Management Approaches. N. Engl. J. Med. 2013, 369, 2021–2030. [Google Scholar] [CrossRef] [PubMed]
  5. Bhutani, V.K.; Wong, R.J. Bilirubin neurotoxicity in preterm infants: Risk and prevention. J. Clin. Neonatol. 2013, 2, 61–69. [Google Scholar] [CrossRef] [Green Version]
  6. Stevenson, D.K.; Vreman, H.J.; Wong, R.J. Bilirubin Production and the Risk of Bilirubin Neurotoxicity. Semin. Perinatol. 2011, 35, 121–126. [Google Scholar] [CrossRef]
  7. Watchko, J.F. Kernicterus and the Molecular Mechanisms of Bilirubin-Induced CNS Injury in Newborns. NeuroMolecular Med. 2006, 8, 513–530. [Google Scholar] [CrossRef]
  8. Ahlfors, C.E.; Wennberg, R.P.; Ostrow, J.D.; Tiribelli, C. Unbound (Free) Bilirubin: Improving the Paradigm for Evaluating Neonatal Jaundice. Clin. Chem. 2009, 55, 1288–1299. [Google Scholar] [CrossRef] [Green Version]
  9. Palmer, N.O.; Bakos, H.W.; Fullston, T.; Lane, M. Impact of obesity on male fertility, sperm function and molecular composition. Spermatogenesis 2012, 2, 253–263. [Google Scholar] [CrossRef] [Green Version]
  10. Chambers, T.J.; Richard, R.A. The impact of obesity on male fertility. Hormones 2015, 14, 563–568. [Google Scholar] [CrossRef]
  11. Katib, A. Mechanisms linking obesity to male infertility. Central Eur. J. Urol. 2015, 68, 79–85. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  12. Ehala-Aleksejev, K.; Punab, M. The effect of metabolic syndrome on male reproductive health: A cross-sectional study in a group of fertile men and male partners of infertile couples. PLoS ONE 2018, 13, e0194395. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  13. Leisegang, K.; Udodong, A.; Bouic, P.J.D.; Henkel, R.R. Effect of the metabolic syndrome on male reproductive function: A case-controlled pilot study. Andrologia 2012, 46, 167–176. [Google Scholar] [CrossRef] [Green Version]
  14. Li, Y.; Liu, L.; Wang, B.; Chen, D.; Wang, J. Nonalcoholic fatty liver disease and alteration in semen quality and reproductive hormones. Eur. J. Gastroenterol. Hepatol. 2015, 27, 1069–1073. [Google Scholar] [CrossRef] [PubMed]
  15. WHO. Manual for the Examination of Human Semen and Semencervical Mucus Interaction, 5th ed.; Cambridge University Press: New York, NY, USA, 2010. [Google Scholar]
  16. WHO. Laboratory Manual for the Examination and Processing of Human Semen, 5th ed.; World Health Organization Press: Geneva, Switzerland, 2010. [Google Scholar]
  17. Brito, M.A.; Brondino, C.D.; Moura, J.J.; Brites, D. Effects of Bilirubin Molecular Species on Membrane Dynamic Properties of Human Erythrocyte Membranes: A Spin Label Electron Paramagnetic Resonance Spectroscopy Study. Arch. Biochem. Biophys. 2001, 387, 57–65. [Google Scholar] [CrossRef]
  18. Brito, M.A.; Brites, D.; Butterfield, D.A. A link between hyperbilirubinemia, oxidative stress and injury to neocortical synaptosomes. Brain Res. 2004, 1026, 33–43. [Google Scholar] [CrossRef] [PubMed]
  19. Hansen, T.W.R.; Nietsch, L.; Norman, E.; Bjerre, J.V.; Hascoet, J.-M.; Mreihil, K.; Ebbesen, F. Reversibility of acute intermediate phase bilirubin encephalopathy. Acta Paediatr. 2009, 98, 1689–1694. [Google Scholar] [CrossRef]
  20. Amin, S.B.; Charafeddine, L.; Guillet, R. Transient Bilirubin Encephalopathy and Apnea of Prematurity in 28 to 32 Weeks Gestational Age Infants. J. Perinatol. 2005, 25, 386–390. [Google Scholar] [CrossRef] [Green Version]
  21. Shapiro, S.M. Chronic bilirubin encephalopathy: Diagnosis and outcome. Semin. Fetal Neonatal Med. 2010, 15, 157–163. [Google Scholar] [CrossRef]
  22. Fernandes, A.; Falcão, A.S.; Silva, R.F.M.; Gordo, A.C.; Gama, M.J.; Brito, M.A.; Brites, D. Inflammatory signalling pathways involved in astroglial activation by unconjugated bilirubin. J. Neurochem. 2006, 96, 1667–1679. [Google Scholar] [CrossRef]
  23. Silva, S.L.; Vaz, A.R.; Barateiro, A.; Falcão, A.S.; Fernandes, A.; Brito, M.A.; Silva, R.F.; Brites, D. Features of bilirubin-induced reactive microglia: From phagocytosis to inflammation. Neurobiol. Dis. 2010, 40, 663–675. [Google Scholar] [CrossRef] [PubMed]
  24. Barateiro, A.; Vaz, A.R.; Silva, S.L.; Fernandes, A.; Brites, R. ER Stress, Mitochondrial Dysfunction and Calpain/JNK Activation are Involved in Oligodendrocyte Precursor Cell Death by Unconjugated Bilirubin. NeuroMol. Med. 2012, 14, 285–302. [Google Scholar] [CrossRef] [PubMed]
  25. Brito, M.A.; Palmela, I.; Cardoso, F.L.; Sá-Pereira, I.; Brites, D. Blood–Brain Barrier and Bilirubin: Clinical Aspects and Experimental Data. Arch. Med Res. 2014, 45, 660–676. [Google Scholar] [CrossRef] [PubMed]
  26. Setchell, B.P. Blood-testis barrier, junctional and transport proteins and spermatogenesis. Adv. Exp. Med. Biol. 2008, 636, 212–233. [Google Scholar]
  27. Boekelheide, K. Mechanisms of Toxic Damage to Spermatogenesis. JNCI Monogr. 2005, 2005, 6–8. [Google Scholar] [CrossRef] [Green Version]
  28. Griswold, M.D. Interactions Between Germ Cells and Sertoli Cells in the Testis. Biol. Reprod. 1995, 52, 211–216. [Google Scholar] [CrossRef]
  29. Su, L.; Mruk, D.D.; Cheng, C.Y. Drug transporters, the blood-testis barrier, and spermatogenesis. J. Endocrinol. 2011, 208, 207–223. [Google Scholar] [CrossRef]
  30. Sodani, K.; Patel, A.; Kathawala, R.J.; Chen, Z.-S. Multidrug resistance associated proteins in multidrug resistance. Chin. J. Cancer 2012, 31, 58–72. [Google Scholar] [CrossRef] [Green Version]
  31. Klein, D.M.; Wright, S.H.; Cherrington, N.J. Localization of Multidrug Resistance-Associated Proteins along the Blood-Testis Barrier in Rat, Macaque, and Human Testis. Drug Metab. Dispos. 2013, 42, 89–93. [Google Scholar] [CrossRef] [Green Version]
  32. Cole, S.P.C. Multidrug resistance protein 1 (MRP1, ABCC1), a “multitasking” ATP-binding cassette (ABC) transporter. J. Biol. Chem. 2014, 289, 30880–30888. [Google Scholar] [CrossRef] [Green Version]
  33. Vorović, J.; Passamonti, S. Membrane Transporters for Bilirubin and Its Conjugates: A Systematic Review. Front. Pharmacol. 2017, 8, 887. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  34. Iorio, A.L.; Da Ros, M.; Fantappiè, O.; Lucchesi, M.; Facchini, L.; Stival, A.; Becciani, S.; Guidi, M.; Favre, C.; De Martino, M.; et al. Blood-Brain Barrier and Breast Cancer Resistance Protein: A Limit to the Therapy of CNS Tumors and Neurodegenerative Diseases. Anti-Cancer Agents Med. Chem. 2016, 16, 810–815. [Google Scholar] [CrossRef] [Green Version]
  35. Mao, Q.; Unadkat, J.D. Role of the Breast Cancer Resistance Protein (BCRP/ABCG2) in Drug Transport—An Update. AAPS J. 2014, 17, 65–82. [Google Scholar] [CrossRef] [Green Version]
  36. Xu, P.; Ling, Z.-L.; Zhang, J.; Li, Y.; Shu, N.; Zhong, Z.-Y.; Chen, Y.; Di, X.-Y.; Wang, Z.-J.; Liu, L.; et al. Unconjugated bilirubin elevation impairs the function and expression of breast cancer resistance protein (BCRP) at the blood-brain barrier in bile duct-ligated rats. Acta Pharmacol. Sin. 2016, 37, 1129–1140. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  37. Bart, J.; Hollema, H.; Groen, H.J.M.; De Vries, E.G.E.; Hendrikse, N.H.; Sleijfer, D.T.; Wegman, T.D.; Vaalburg, W.; Van Der Graaf, W.T.A. The distribution of drug-efflux pumps, P-gp, BCRP, MRP1 and MRP2, in the normal blood-testis barrier and in primary testicular tumours. Eur. J. Cancer 2004, 40, 2064–2070. [Google Scholar] [CrossRef]
  38. Kalliokoski, A.; Niemi, M. Impact of OATP transporters on pharmacokinetics. Br. J. Pharmacol. 2009, 158, 693–705. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  39. van de Steeg, E.; Wagenaar, E.; van der Kruijssen, C.M.; Burggraaff, J.E.; de Waart, D.R.; Elferink, R.P.O.; Kenworthy, K.E.; Schinkel, A.H. Organic anion transporting polypeptide 1a/1b-knockout mice provide insights into hepatic handling of bilirubin, bile acids, and drugs. J. Clin. Investig. 2010, 120, 2942–2952. [Google Scholar] [CrossRef]
  40. Suzuki, T.; Onogawa, T.; Asano, N.; Mizutamari, H.; Mikkaichi, T.; Tanemoto, M.; Abe, M.; Satoh, F.; Unno, M.; Nunoki, K.; et al. Identification and Characterization of Novel Rat and Human Gonad-Specific Organic Anion Transporters. Mol. Endocrinol. 2003, 17, 1203–1215. [Google Scholar] [CrossRef] [Green Version]
  41. Augustine, L.M.; Markelewicz, R.J.; Boekelheide, K.; Cherrington, N.J. Xenobiotic and endobiotic transporter mRNA expression in the blood-testis barrier. Drug Metab. Dispos. 2005, 33, 182–189. [Google Scholar] [CrossRef] [Green Version]
Table
Table 1. Characteristics of participants in serum total bilirubin quartiles.
Table 1. Characteristics of participants in serum total bilirubin quartiles.
VariablesQ1
(n = 2298)		Q2
(n = 2230)		Q3
(n = 2277)		Q4
(n = 2252)		p-Value
Continuous variables, mean (SD)
Age (years)32.33 (4.67)32.35 (4.89)32.01 (4.55)32.01 (4.79)<0.05
Total bilirubin0.56 (0.10)0.79 (0.06)1.01 (0.07)1.50 (0.38)<0.05
SBP119.35 (14.51)120.76 (13.04)120.72 (11.65)118.81 (13.67)0.74
FPG98.52 (12.11)98.29 (15.34)97.59 (14.30)96.60 (11.82)<0.05
AST24.35 (11.53)24.89 (11.51)25.29 (17.24)24.94 (18.46)0.21
CHO190.39 (34.52)192.53 (35.37)190.97 (38.00)187.84 (32.82)<0.05
CRP (mg/dL)0.28 (0.51)0.20 (0.30)0.20 (0.62)0.18 (0.37)<0.05
Continuous variables, median (IQR)
Sperm concentration49.78 (36.33)53.48 (42.29)55.46 (44.13)53.94 (41.20)<0.05
Sperm total motility (%)64.07 (16.16)64.71 (16.65)64.97 (15.67)63.66 (16.71)<0.05
Sperm progressive motility (%)45.49 (16.56)46.42 (17.27)46.53 (16.60)45.29 (16.92)<0.05
Sperm normal morphology (%)66.16 (16.69)66.91 (16.44)67.55 (15.83)67.50 (16.86)<0.05
Category variables, (%)
HTN (%)54 (2.4)53 (2.4)47 (2.1)58 (2.8)0.80
DM (%)13 (0.6)12 (0.5)13 (0.6)6 (0.3)0.19
Cigarette smoking (%)239 (40.9)266 (50.2)304 (52.6)364 (58.4)<0.05
SD, standard deviation; SBP, systolic blood pressure; FPG, fasting plasma glucose; AST, aspartate aminotransferase; CHO, cholesterol; CRP, C-reactive protein; HTN, hypertension; DM, type II diabetes mellitus.
Table
Table 2. Association between serum total bilirubin and sperm quality.
Table 2. Association between serum total bilirubin and sperm quality.
VariablesModel 1 a
β (95% CI)		p
Value		Model 2 a
β (95% CI)		p
Value		Model 3 a
β (95% CI)		p
Value		Model 4 a
β (95% CI)		p
Value
Sperm Concentration
Total bilirubin−6.40 (−35.10, 22.31)0.661.44 (−26.60, 29.47)0.923.50 (−25.58, 32.57)0.813.02 (−27.80, 33.85)0.84
Sperm Motility
Total bilirubin−7.41 (−20.68, 5.86)0.27−12.11 (−24.45, 0.23)<0.05−12.13 (−24.74, 0.47)<0.05−13.82 (−26.99, −0.64)<0.05
Sperm Progressive Motility
Total bilirubin−8.28 (−22.25, 5.69)0.24−12.06 (−25.71, 1.60)0.08−10.91 (−25.21, 3.38)0.13−12.73 (−27.70, 2.24)0.09
Sperm Normal Morphology
Total bilirubin−16.75 (−27.53, −5.96)<0.05−17.89 (−29.01, −6.76)<0.05−17.46 (−28.95, −5.97)<0.05−18.38 (−30.46, −6.29)<0.05
a Adjusted covariates: Model 1: unadjusted. Model 2: Model 1 + age. Model 3: Model 2 + AST, CHO, CRP, FPG, and SSL. Model 4: Model 3 + HTN, cigarette smoking.
Table
Table 3. Association between quartiles of serum total bilirubin and sperm quality.
Table 3. Association between quartiles of serum total bilirubin and sperm quality.
VariablesModel 1 a
OR b (95% CI)		p
Value		Model 2 a
OR b (95% CI)		p
Value		Model 3 a
OR b (95% CI)		p
Value		Model 4 a
OR b (95% CI)		p
Value
Sperm Concentration
Q2 vs. Q17.13 (−25.46, 39.72)0.667.78 (−23.25, 38.81)0.6211.55 (−20.55, 43.65)0.4711.98 (−20.98, 44.94)0.47
Q3 vs. Q19.06 (−20.88, 39.00)0.5512.57 (−16.09, 41.24)0.3823.91 (−7.61, 55.43)0.1325.76 (−7.26, 58.77)0.12
Q4 vs. Q1−9.80 (−42.39, 22.79)0.55−2.14 (−33.87, 29.59)0.89−2.81 (−34.93, 29.30)0.86−4.18 (−37.26, 28.91)0.80
Sperm Motility
Q2 vs. Q12.67 (−12.49, 17.83)0.722.26 (−11.39, 15.91)0.745.14 (−8.77, 19.05)0.465.25 (−8.90, 19.40)0.46
Q3 vs. Q10.74 (−13.19, 14.67)0.92−1.45 (−14.06, 11.16)0.822.23 (−11.43, 15.89)0.743.67 (−10.51, 17.84)0.60
Q4 vs. Q1−7.93 (−23.09, 7.23)0.30−12.72 (−26.68, 1.24)0.07−13.31 (−27.22, 0.61)0.06−14.15 (−28.36, 0.06)<0.05
Sperm Progressive Motility
Q2 vs. Q1−5.53 (−21.64, 10.57)0.49−5.85 (−21.20, 9.50)0.45−3.67 (−20.01, 12.67)0.65−3.72 (−20.42, 12.98)0.65
Q3 vs. Q1−4.01 (−18.81, 10.78)0.59−5.73 (−19.91, 8.45)0.42−2.56 (−18.61, 13.49)0.75−0.99 (−17.72, 15.74)0.91
Q4 vs. Q1−9.83 (−25.94, 6.27)0.23−13.58 (−29.28, 2.11)0.09−13.22 (−29.57, 3.12)0.11−13.99 (−30.76, 2.77)0.10
Sperm Normal Morphology
Q2 vs. Q1−7.32 (−19.68, 5.05)0.24−7.40 (−19.84, 5.03)0.24−4.78 (−17.30, 7.75)0.44−5.04 (−17.84, 7.75)0.43
Q3 vs. Q1−3.81 (−15.17, 7.55)0.50−4.28 (−15.76, 7.21)0.460.46 (−11.83, 12.76)0.941.65 (−11.17, 14.46)0.80
Q4 vs. Q1−18.62 (−30.98, −6.25)<0.05−19.64 (−32.35, −6.92)<0.05−20.79 (−33.32, −8.26)<0.05−21.15 (−33.99, −8.30)<0.05
a Adjusted covariates: Model 1: unadjusted, Model 2: Model 1 + age, Model 3: Model 2 + AST, CHO, CRP, FPG, SSL, Model 4: Model 3 + HTN, cigarette smoking. β b was interpreted as change of sperm quality for each increase in total bilirubin.
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Chen, Y.-Y.; Chen, W.-L. Serum Bilirubin and Sperm Quality in Adult Population. Toxics 2022, 10, 295. https://doi.org/10.3390/toxics10060295

AMA Style

Chen Y-Y, Chen W-L. Serum Bilirubin and Sperm Quality in Adult Population. Toxics. 2022; 10(6):295. https://doi.org/10.3390/toxics10060295

Chicago/Turabian Style

Chen, Yuan-Yuei, and Wei-Liang Chen. 2022. "Serum Bilirubin and Sperm Quality in Adult Population" Toxics 10, no. 6: 295. https://doi.org/10.3390/toxics10060295

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