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Nutritional geometry of mitochondrial genetic effects on male fertility.

ABSTRACT: Organismal fitness is partly determined by how well the nutritional intake matches sex-specific metabolic requirements. Metabolism itself is underpinned by complex genomic interactions involving products from both nuclear and mitochondrial genomes. Products from these two genomes must coordinate how nutrients are extracted, used and recycled, processes vital for fuelling reproduction. Given the complicated nature of metabolism, it is not well understood how the functioning of these two genomes is modulated by nutrients. Here we use nutritional geometry techniques on Drosophila lines that only differ in their mtDNA, with the aim to understand if there is nutrient-dependent mitochondrial genetic variance for male reproduction. We first find genetic variance for diet consumption, indicating that flies are consuming different amounts of food to meet new physiological requirements. We then find an interaction between mtDNA and diet for fitness, suggesting that the mtDNA plays a role in modulating diet-dependent fitness. Our results enhance our basic understanding of nutritional health and our chimeric genomes.

SUBMITTER: Camus MF

PROVIDER: S-EPMC7058949 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Nutritional geometry of mitochondrial genetic effects on male fertility.

Camus M F MF Moore J J Reuter M M

Biology letters 20200226 2

Organismal fitness is partly determined by how well the nutritional intake matches sex-specific metabolic requirements. Metabolism itself is underpinned by complex genomic interactions involving products from both nuclear and mitochondrial genomes. Products from these two genomes must coordinate how nutrients are extracted, used and recycled, processes vital for fuelling reproduction. Given the complicated nature of metabolism, it is not well understood how the functioning of these two genomes i ...[more]

PMID: 32097597

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Project description:IntroductionInfertility is a worldwide problem and about 10%-15% of all couples will be affected by the inability to have children. In approximately 50% of infertile couples, a male factor is involved. Most of the male infertile cases are characterised as 'idiopathic', except for a small percentage of cases which are causative by a genetic aetiology. In the past decade, the role of oxidative stress related to sperm quality has been researched thoroughly and estimated to be the problem in 25%-87% of male infertility cases. Impryl is a nutritional supplement which works on the metabolic system and the regulation of oxidative stress by activating the 1-carbon cycle and therefore recycling of homocysteine. We hypothesise that the nutritional supplement Impryl in men of infertile couples might improve the ongoing pregnancy rate.Methods and analysisWe designed a multicentre, randomised, double-blind, placebo-controlled clinical trial. We aimed to include 1200 male adults aged 18-50 years, part of a couple that is diagnosed with infertility. The couple will either start or has already been started with fertility treatment, that is, expectative management (duration of 6 months), intrauterine insemination (IUI) with or without mild ovarian stimulation or ovulation induction, either in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI) treatment. Male participants will be randomised in either the Impryl or the placebo group, with identical appearance of the tablets to be distributed (doses: one tablet each day), for a total duration of maximal 6 months. Patients can start directly with fertility treatment and/or natural conception. The primary outcome is the number of ongoing pregnancies confirmed by ultrasound at ≥10 to 12 weeks, and conceived in the time window between randomisation up to and including month 6 of intervention use. Secondary outcomes are change in semen parameters between baseline and after 3 months of intervention in the IUI/IVF/ICSI group, based on (prewash) total motile sperm count. Furthermore the number of pregnancies conceived in the optimal intervention time window (after full spermatogenesis of 72 days), overall number of pregnancies, time to pregnancy, embryo fertilisation rate in IVF/ICSI, embryo-utilisation rate in IVF/ICSI, number of miscarriages, live birth rate and adverse events are documented within the study period of 15 months.Ethics and disseminationThe protocol is approved by the local medical ethical review committee at the Radboud University Medical Centre and by the national Central Committee on Research Involving Human Subjects. Findings will be shared with the academic and medical community, funding and patient organisations in order to contribute to optimisation of medical care and quality of life for patients with infertility.Trial registration numbersNCT03337360 and NTR6551.

Dataset Information

Nutritional geometry of mitochondrial genetic effects on male fertility.

Publications

Nutritional geometry of mitochondrial genetic effects on male fertility.

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