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Familial resemblance in markers of testicular function in fathers and their young sons: a cross-sectional study

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STUDY QUESTION: Is testicular function associated within father-son pairs?

SUMMARY ANSWER: Familial resemblance in testis volume and serum markers of spermatogenesis was observed in father-son pairs.

WHAT IS KNOWN ALREADY: Studies suggest familial clustering of male subfertility and impaired spermatogenesis, but in men from the general population little is known about concordance in testicular function between fathers and sons.

STUDY DESIGN, SIZE, DURATION: This cross-sectional study with simultaneous collection of data in fathers and sons included 72 pairs (144 fathers and sons), unselected regarding testicular function were included.

PARTICIPANTS/MATERIALS, SETTING, METHODS: A subgroup of men from the background population and participating in a study on testicular function were asked permission to invite their fathers to participate in a similar setup. Fathers (median age of 53 years) and sons (median age of 19 years) participated in the same study setup including assessment of testis size, having a blood sample taken and analysed for serum levels of reproductive hormones (FSH, inhibin B, LH, testosterone, oestradiol, sex hormone-binding globulin (SHBG) and calculated free testosterone) and delivering a semen sample for assessment of traditional semen parameters. Mixed-effects models were fitted to estimate the familial resemblance as the proportion of variance in markers of testicular function due to shared factors for fathers and sons accounted for using random-effects. Variance components were calculated from both unadjusted and adjusted models.

MAIN RESULTS AND THE ROLE OF CHANCE: After adjustments, variance component analyses showed that familial resemblance between fathers and sons accounted for 48% (P < 0.001) of the variation in testicular volume, 32% (P = 0.009) of the variation in FSH, 31% (P = 0.009) of the variation in the inhibin B/FSH ratio, 33% (P = 0.007) and 45% (P < 0.001) of the variation in testosterone and free testosterone, respectively, and 31% (P = 0.009) of the variation in SHBG. None of the semen parameters were associated within father-son pairs.

LIMITATIONS, REASONS FOR CAUTION: The present study may have lacked power to detect associations for semen quality, as large intra- and inter-individual variation occur in semen parameters.

WIDER IMPLICATIONS OF THE FINDINGS: In this study, testis volume, serum testosterone and serum markers of spermatogenesis including FSH were associated in fathers and sons, suggesting an impact of paternal genetics for testicular function in the son. However, the estimated familial resemblance for spermatogenesis markers highlights that other factors, such as maternal genetics and prenatal as well as adult exposures, are also of major importance for testicular function.

STUDY FUNDING/COMPETING INTEREST(S): The study has received funding from Danish Health Authority, Research Fund of the Capital Region of Denmark and Independent Research Fund Denmark (8020-00218B). None of the funders had any role in the study design, collection, analysis or interpretation of data, writing of the paper of publication decisions. The authors have nothing to disclose.

TRIAL REGISTRATION NUMBER: N/A.

Original languageEnglish
JournalHuman reproduction (Oxford, England)
Volume36
Issue number3
Pages (from-to)543-550
Number of pages8
ISSN0268-1161
DOIs
Publication statusPublished - 2021

ID: 62033370