Homocysteine-Thiolactone links metabolic stress to ovarian function by regulating steroid biosynthesis and receptor expression

Introduction: Elevated homocysteine leads to increased levels of homocysteine thiolactone (HCTL), a highly active thioester that alters protein structure and function by N-homocysteinylation. The most common causes for elevated homocysteine/HCTL are malnutrition and MTHFR mutations. Having reported that the 677 C >T MTHFR mutation is associated with poor ovarian response in patients undergoing controlled ovarian stimulation, we investigated the effect of HCTL on granulosa cell biology. Methods: Pooled cultures (collected from 5 – 10 patients) of human primary granulosa cells (GCs) were used in the current study.…