HIGD1A Alleviates Oxidative Stress Related Ovarian Hypofunction by Enhancing Granulosa Cell Functions via NF‐κB/SOD2 Signaling Pathway

Abstract Diminished ovarian reserve (DOR) is a physiological or pathological condition that progresses in an age‐dependent manner, which is characterized by impaired ovarian follicle quality, decreased anti‐Müllerian hormone levels, elevated follicle‐stimulating hormone levels, and reduced antral follicle counts. Oxidative stress (OS) is one of the culprits of DOR. By imposing OS damage on various kinds of ovarian cells including granulosa cells, OS can result in ovarian hypofunction and eventually lead to female infertility. However, the underlying mechanisms have not been fully elucidated yet. In this study, HIGD1A, a mitochondrial inner membrane component, is found to be downregulated in granulosa cells upon OS exposure. By systematically studying the role of HIGD1A in regulating granulosa cell and ovarian functions as well as its corresponding mechanisms, a novel regulatory mechanism underlying OS‐related female infertility is revealed, and provided a potential molecular target for anti‐OS therapies.