Abstract
Abstract
STUDY QUESTION
What are the individual and combined effects of a common genetic cause of human male infertility (loss of M1AP function) and a negative lifestyle factor (a Western diet) on male fertility, spermatogenesis, and sperm quality in mice?
SUMMARY ANSWER
The loss of M1AP and a Western diet separately led to subfertility (a form infertility) in male mice and in combination subfertility was worsened.
WHAT IS KNOWN ALREADY
Genetics and lifestyle factors individually play important roles in male infertility aetiology. How lifestyle factors influence common genetic causes of infertility are unknown.
STUDY DESIGN, SIZE, DURATION
We generated knockout M1ap mice (M1ap−/−-) and investigated the effects of genotype (wild type or knockout) and diet (control or Western diet) or genotype and age (young or aged) on male fertility and sperm parameters.
PARTICIPANTS/MATERIALS, SETTINGS, METHODS
C57BL6/J mice: wild type (M1ap+/+) and M1ap knockout (M1ap−/−) at 10–12 (young) weeks or 26–28 weeks old (aged), on a control of Western (high-fat and high-sugar) diet and age. We evaluated male fertility, testis and epididymis histology, and sperm quality (motility, morphology, and count).
MAIN RESULTS AND THE ROLE OF CHANCE
Compared to the individual gene deletion or diet treatments, the combined M1ap−/− and Western diet group had more abnormal germ cells, sloughed germ cells and resulted in fewer pups per litter. In accordance, sperm motility and morphology in the combination group were more significantly compromised compared to individual experimental groups.
LARGE SCALE DATA
N/A.
LIMITATIONS, REASONS FOR CAUTION
While the mutant mouse mimics the genetic variants seen in many infertile men, this is a mouse model study, meaning findings should be validated in a human cohort where possible.
WIDER IMPLICATIONS OF THE FINDINGS
Taken together, our data highlight that genetic and lifestyle factors can interact to exacerbate male infertility. This study sets a precedent for an improved consideration of how genetic, lifestyle and environmental factors contribute to infertility aetiology. These data inform a clinical foundation for lifestyle interventions for men presenting at infertility clinics prior to medically assisted reproduction.
FUNDING
This project was supported by a Society for Reproductive Biology Career Development Award to B.J.H., National Health and Medical Research Council project grant (APP1120356) awarded to M.K.O.B., an Australia–Germany Joint Research Co-operation Scheme (UA-DAAD) grant (57511796) awarded to M.K.O.B., J.E.M.D., and F.T., and the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) within the Clinical Research Unit ‘Male Germ Cells’ (CRU326, project number 329621271) awarded to F.T. and C.F.
DISCLOSURES
N/A.