Table 1.

Roles of autophagy in diseases with sex differences

Diseases	Roles of autophagy	Genes	Ref.
Cancers	A role for increased autophagy in prostate cancer progression. AR signalling promotes adaptation to nutrient starvation and, in turn, evasion of cell death. 2-Methoxyestradiol induces autophagy in colon carcinoma. Autophagy acts as a tumor suppressor in hepatocellular, breast, ovarian, and prostate cancer.	AR AR, HSPA5 CYP19A1 BECN1	[78] [91] [92] [18, 93]
Cardiovascular diseases	In cardiac atrophy, males lose more cardiac muscle than do females in cancer, and autophagy is the main proteolytic pathway involved. In cardiac ischemia-reperfusion (I-R)-induced injury, autophagy is upregulated in females. Enhancing autophagy protects against I-R injury in the heart. Ischemia stimulates autophagy via AMPK. Glycogen autophagy (glycophagy) is an important component of the response to cardiac metabolic stress in females. Sex steroids regulate autophagy during myocardial infarction. In coxsackievirus B3-induced myocarditis, sex-biased autophagy occurs in the heart, with females being substantially less susceptible than males.	ESR, LC3B LC3B BECN1 AMPK, BECN1 STBD1, AMPK AR, MTOR ATG5	[94] [56] [10] [95] [96] [11 [97]
Chronic pancreatitis	Chronic pancreatitis is more common among men; impaired autophagy triggers chronic pancreatitis.	ATG5	[98]
Neural system diseases	Defective hypothalamic autophagy promotes obesity. FBXW7-AS1/DEspR haploinsufficiency with increased neuronal autophagy and cognitive decline in males. ESR1 inhibits autophagy, leading to less severity of iron-induced brain injury in females than in males. Lower levels of autophagy, increased risk of AD, and greater severity of pathology in women. Decreased mitophagy in neonatal hypoxic-ischemic encephalopathy in males. SNPs of ATG16L1 are associated with ankylosing spondylitis in females.	ATG7, IKBKB EDN1 ESR1, ATG7 MTOR, ESR1 LAMP2, TOMM20 ATG16L1	[99] [100] [101] [24] [102] [103]
Obesity	Activation of autophagy in placentas of males but not females from obese women.	ATG7	[32]
Osteoporosis	Autophagy deficiency aggravates the bone loss associated with ageing and decreased estrogen levels in women	LC3B, ATG5	[104]
Bowel diseases	In Crohn disease (CD), female-specific CD association in ATG16L1.	ATG16L1	[105,106]
Reproductive diseases	BECN1 deficiency in the ovary results in the reduction of progesterone production and preterm labor. Decreased autophagy in the endometrium of women with polycystic ovary syndrome. Disruption of autophagy by the Sertoli cell-specific knockout of ATG5 or ATG7 causes male subfertility.	BECN1 ATG3, ATG14 ATG5, ATG7, PDLIM1	[52] [26] [106]