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. 2022 Nov 2:13:1035338.
doi: 10.3389/fendo.2022.1035338. eCollection 2022.

Type 2 diabetes mellitus and the risk of abnormal spermatozoa: A Mendelian randomization study

Mengyuan Dai  1   2 , Weijie Guo  1   2 , San Zhu  1   2 , Guidong Gong  1 , Mei Chen  1 , Zhuoling Zhong  1   2 , Junling Guo  1   3 , Yaoyao Zhang  1   2
Affiliations

Type 2 diabetes mellitus and the risk of abnormal spermatozoa: A Mendelian randomization study

Mengyuan Dai et al. Front Endocrinol (Lausanne). .

Abstract

Abnormal spermatozoa can not only reduce the fertilization rate, but also prolong the natural conception time and even increase the risk of spontaneous miscarriage. Diabetes mellitus (DM) has become a major global health problem, and its incidence continues to rise, while affecting an increasing number of men in their reproductive years. Type 2 Diabetes Mellitus (T2DM), accounting for about 85-95% of DM, is closely related to the development of sperm. However, the exact association between T2DM and abnormal spermatozoa remains unclear. Herein, we designed a Two-sample Mendelian randomization (MR) study to explore the causal association between T2DM and abnormal spermatozoa risk in European population data which come from the GWAS summary datasets. We selected 9 single nucleotide polymorphisms (SNPs) of T2DM (exposure data) as instrumental variables (IVs), and then retrieved the suitable abnormal spermatozoa genome-wide association study (GWAS) data of European from Ieu Open GWAS Project database which includes 915 cases and 209,006 control as the outcome data. Our results indicate that strict T2DM might not result in a higher risk of abnormal spermatozoa genetically in Europeans (OR: 1.017, 95% confidence interval (CI): 0.771-1.342, p=0.902). Our findings demonstrate that only T2DM may not explain the relatively higher risk of abnormal spermatozoa in men with it in Europeans. In subsequent studies, more comprehensive and larger samples need to be studied to reveal the relationship and potential mechanism between T2DM and abnormal spermatozoa.

Keywords: GWAS; Mendelian randomization; SNPs; T2DM; abnormal spermatozoa.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer FQ declared a shared affiliation with the authors to the handling editor at the time of review.

Figures

Figure 1
Figure 1
Direct Acyclic Graph of an MR analysis. The hypothesis that outcomes (abnormal spermatozoa) are caused by the exposure (T2DM) can be estimated by 2TSMR analysis. The genetic variants used in 2TSMR analysis must: a) be strongly associated with T2DM, b) be not associated with any confounder of T2DM and abnormal spermatozoa, c) be not related to the relevant outcomes obtained through other methods.
Figure 2
Figure 2
Scatter plot illustrating the distribution of individual ratio estimates of T2DM with abnormal spermatozoa as the outcome. Trend lines derived from five different 2SMR methods are also included in each scatter plot to indicate cause and effect.
Figure 3
Figure 3
Leave-one-out sensitivity analysis for T2DM on abnormal spermatozoa. The given dark dots indicate effect measures from IVW-MR analysis excluding specific SNPs. Red lines indicate pooled analysis including all SNPs by the IVW-MR method (plotted for comparison).
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