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LIG4 and Male Fertility: What Your Genotype Means for Sperm Health

DNA ligase IV, encoded by the LIG4 gene, helps repair DNA double strand breaks that occur during sperm development. When this repair process is less efficient, sperm can end up with higher DNA damage, lower counts, or reduced motility, and that can increase the risk of infertility. Your rs1805388 genotype can influence how well LIG4 performs.

How to read this report

This article explains how different rs1805388 genotypes may affect sperm DNA repair and fertility risk, and gives practical, evidence-informed steps you can take to support sperm health. PlexusDx does not provide medical advice. Always discuss genetic results and health decisions with your healthcare provider.

Genetic interpretations

AA genotype (two effect alleles)

Carrying two copies of the A allele at rs1805388 is associated with reduced DNA ligase IV activity. This may lead to less efficient repair of DNA breaks during spermatogenesis and a higher chance of sperm DNA damage, lower sperm count, and reduced motility compared with typical function.

What you can do

  • Prioritize an antioxidant rich diet: berries, leafy greens, cruciferous vegetables, nuts, and colorful fruits to help reduce oxidative damage to sperm DNA.
  • Consider supplements that support sperm health: N-Acetyl Cysteine 600 to 1200 mg/day, Vitamin C 500 mg or more/day, CoQ10 100 to 200 mg/day, L-carnitine 1 to 2 g/day, and zinc 15 to 30 mg/day. Discuss doses with your clinician before starting.
  • Avoid testicular heat exposure: no hot tubs or saunas and avoid prolonged laptop-on-lap use.
  • Stop smoking, limit alcohol, and reduce exposure to environmental toxins and pesticides.
  • Maintain healthy weight, manage stress, prioritize 7 to 9 hours sleep per night, and engage in moderate regular exercise.
  • If fertility is a concern, consider semen analysis and sperm DNA fragmentation testing; consult a reproductive specialist as needed.
AG genotype (one effect allele)

Carrying one A allele may modestly reduce DNA ligase IV function during sperm development. This can slightly increase the likelihood of sperm DNA damage, lower count, or reduced motility compared with people who do not carry the effect allele, though many carriers have normal fertility.

What you can do

  • Adopt an antioxidant first diet: include berries, leafy greens, cruciferous vegetables, nuts, legumes, and whole grains to support cellular repair.
  • Supplements that may help: N-Acetyl Cysteine, Vitamin C, CoQ10, L-carnitine, and zinc. Speak with your healthcare provider about appropriate dosing and interactions.
  • Reduce heat and toxin exposures, avoid tobacco, and limit excessive alcohol.
  • Optimize lifestyle: healthy weight, stress reduction, consistent sleep, and moderate activity support hormone balance and sperm quality.
  • If you are planning a pregnancy or have concerns, a semen analysis can give a baseline and guide next steps with your clinician.
GG genotype (no effect alleles)

With two copies of the G allele, LIG4 function is expected to be typical. Your risk of infertility related to this specific variant is not elevated. Normal DNA repair activity supports standard spermatogenesis and sperm DNA integrity.

What you can do

  • Continue to support sperm health through an antioxidant rich diet: berries, leafy greens, nuts, cruciferous vegetables, and omega 3 rich foods such as fatty fish or algae sources.
  • Maintain healthy lifestyle habits: avoid heat to the testes, minimize toxin exposures, avoid smoking, limit alcohol, manage stress, keep a healthy weight, get adequate sleep, and exercise regularly.
  • Consider periodic semen analysis if you have reproductive plans or risk factors such as prior infections, undescended testes, or occupational exposures.

Dietary and supplement guidance

Nutrition plays a key role in protecting sperm DNA and supporting overall sperm quality. Focus on whole foods that provide antioxidants, healthy fats, and micronutrients that are particularly important for sperm function.

  • Antioxidant rich foods: berries, cherries, citrus, dark leafy greens, tomatoes, bell peppers, and cruciferous vegetables.
  • Healthy fats: fatty fish, walnuts, chia or flax seeds, and olive oil to support membrane health and hormone production.
  • Micronutrient sources: oysters, lean meats, beans, seeds, and fortified cereals for zinc, selenium, folate, and B vitamins.
  • Hydration: adequate fluid intake supports semen volume and concentration.

Supplements sometimes used to support sperm health include

  • N-Acetyl Cysteine 600 to 1200 mg/day
  • Vitamin C 500 mg or more/day
  • Coenzyme Q10 100 to 200 mg/day
  • L-carnitine 1 to 2 g/day
  • Zinc 15 to 30 mg/day

Discuss supplements with your healthcare provider to confirm suitability, dosing, and interactions with medications or medical conditions.

Lifestyle actions that support sperm DNA and fertility

  • Avoid heat exposure to the testes: brief periods at elevated temperature can impair sperm production for several months.
  • Stop smoking and reduce alcohol intake: both are associated with worse sperm parameters and increased DNA damage.
  • Limit exposure to environmental toxins: reduce contact with pesticides, solvents, and heavy metals relevant to your occupation or home environment.
  • Maintain a healthy weight: both underweight and overweight can affect hormone balance and sperm quality.
  • Manage stress and prioritize sleep: chronic stress and poor sleep can disrupt hormones that regulate sperm production.
  • Exercise moderately: regular physical activity supports hormonal health; avoid excessive endurance training that may impair fertility.

When to seek testing or specialist care

  • After 12 months of trying to conceive without success, or after 6 months if you are over age 35, consult your healthcare provider for evaluation.
  • Consider a semen analysis to assess count, motility, morphology, and volume.
  • If semen parameters are abnormal or if you have recurrent pregnancy loss with a partner, discuss sperm DNA fragmentation testing and referral to a reproductive specialist or urologist.
  • If you have known exposures, prior chemotherapy, a history of testicular injury, undescended testes, or genetic concerns, raise these early with your clinician.

Bottom line

Variants in LIG4 can influence how effectively sperm DNA is repaired. If you carry one or two copies of the effect allele at rs1805388, you may have a higher risk of sperm DNA damage and related fertility issues, but many lifestyle and nutritional steps can help protect sperm health. If your genotype does not carry the effect allele, standard fertility protective practices remain important.

Important: PlexusDx does not provide medical advice. This information is educational only. Discuss your genetic results, supplements, tests, and treatment options with your healthcare provider to determine the best plan for your health and fertility goals.