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Homocysteine & Infertility

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Homocysteine & Infertility
Infertility/ Subfertility
• one year of unprotected intercourse with the same partner without conception.

• 10-15 % of couples • Multifactorial

infertility

male tubal & peritoneal ovulatory

cervical & other

Homocysteine & Fertility
Dr. S. Bhanu Rekha Assoc. Prof SVS

Pioneers

Dr .Vigneaud 1933

Dr .Kilmer Mc Cully 1968

What is Homocysteine ?
Protein diet Digestion
Metabolism Methionine Auto-oxidation Protein synthesis 2)Homocystine 1)Homocysteine

HS-CH2-CH2-CH-COOH NH2 Homocysteine
• Sulfur-containing amino acid •By product of methionine metabolism

3) Homocysteine thiolactone
Generation of ROS • 1+2+3= homocyst(e)ine
•homocyst(e)ine = tHcy •Homocyst(e)inemia=hyper - tHcy

peptides

B12 d UMP to d TMP

Pyridoxine B6

C lyase

Homocysteine : Metabolic Pathways
Remethylation Cycle Tetra hydrofolate
Folic acid MTHFR Vitamin B12 (MS)

Diet Methionine

Demethylation
Cycle

Methyl tetrahydrofolate

Homocysteine Cystathionine

Vitamin B6 (C beta S)

MS – Methionine synthase MTHFR – Methyl tetrahydro folate reductase C beta S – Cystathionine beta synthase

Cysteine Sulphate Glutathione

Increase homocysteine concentration
Methionine Methyl transferase Homocysteine
Cystathionine

MTHFR 【Genetic deficiency】

synthase

Vitamin B6 Cystathionin e Vitamin B6 Cysteine

【nutritional deficiencies, life style , drugs , some diseases 】

Cystathionine

synthase

Journal of Nephrology. 15(4):414-21, 2002

PATHOGENESIS OF HYPERHOMOCYSTEINEMIA
PRO INFLAMMATORY CYTOKINES
• MONOCYTE CHEMOATTRACTANT PROTEIN • IL-8 –neutrophils, T-Lymphocytes

NITRIC OXIDE – NO/eNOs
• Accelerated inactivation • Increase in serum.assymetricdimethylarginine- endogenous inhibitor of eNOs

REACTIVE OXYGEN SPECIES - ROS
• O2- , OH-, • Inhibition of cellular antioxidant enzymes

UPR in ER – activation of unfolded protein response Defective Methylation of DNA & proteins

Male infertility
Gene mutation MTHFR c677T ass with unexplained infertility (park et al 2005) Folate – cellular cohesion with
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