Research Progress on the Relationship between Obesity‐Inflammation‐Aromatase Axis and Male Infertility

Abstract

Aromatase is a key enzyme in the transformation of androgen into estrogen. Its high expression will destroy the hormonal balance in the male body, and the excessive transformation of androgen into estrogen in the body will further damage the spermatogenic function of the testis, affect the normal development of the sperm, and cause spermatogenic disturbance. Adipose tissue has a high expression of aromatase and shows high enzymatic activity and ability to convert estrogen. Adipose tissue is the most estrogen-producing nongonadal tissue in the body because of its large size, accounting for about 20% of the body mass in healthy adults. PPARγ is recognized as the key adipose differentiation in the transcriptional regulation of the transcription factor. In the process of adipocyte differentiation, PPARγ regulate the expression of aromatase. The increase of aromatase is associated with the inflammatory response in adipose tissue caused by obesity. After obesity, the increase of proinflammatory factors in adipocytes will lead to enhanced transcription of the CYP19 gene encoding aromatase in adipocytes, which in turn will lead to increased expression of aromatase in adipocytes. This article reviews the regulation of male sterility from the angle of the “obesity-inflammation-aromatase” axis.

Fatty Acid Oxidation and Pro-Resolving Lipid Mediators Are Related to Male Infertility

“…The high content of PUFAs in the sperm plasma membrane, makes them susceptible to lipid peroxidation in presence of oxidative stress (OS) [ 13 ]. Male infertility may be due to an inflammation-mediated OS including varicocele, tobacco usage, alcohol, obesity/metabolic syndrome, leukocytospermia, sexually transmitted disease, bacterial prostatitis, and viral infections [ 14 , 15 , 16 , 17 ]. Inflammation status may be associated also with idiopathic infertility [ 18 ].…”

Very low‐calorie ketogenic diet rapidly augments testosterone levels in non‐diabetic obese subjects

“…31 Second, the increased aromatase activity observed in supernumerary adipocytes could lead to a higher degree of testosterone conversion to oestradiol, leading to relative hyperoestrogenism that may subsequently reduce serum testosterone levels through its inhibitory effect on LH secretion. 32 Third, elevated leptin levels observed in obese subjects could inhibit GnRH pulsatility, leading to hypogonadotropic hypogonadism. 5 Finally, the role of inflammation in linking hypogonadism and obesity has been recently proposed.…”

“…First, insulin resistance typically observed in obese patients is associated with reduced serum SHBG levels, higher testosterone levels with increased aromatisation in fat tissue, and reduced bioavailable steroids 31 . Second, the increased aromatase activity observed in supernumerary adipocytes could lead to a higher degree of testosterone conversion to oestradiol, leading to relative hyperoestrogenism that may subsequently reduce serum testosterone levels through its inhibitory effect on LH secretion 32 . Third, elevated leptin levels observed in obese subjects could inhibit GnRH pulsatility, leading to hypogonadotropic hypogonadism 5 .…”

Association of сarriage of the rs4646994 polymorphism of the ACE gene with obesity and androgen deficiency in men

“…Выявлена также связь между АнД и инсулинорезистентностью, дислипидемиями, метаболическим синдромом (МС), риском сосудистых осложнений [6,7]. При ожирении интенсивность процессов формирования возрастного АнД у мужчин дополнительно повышается в связи с конвертацией ароматазой адипоцитов жировой ткани тестостерона в эстрадиол [8]. В свою очередь, формирующийся АнД способствует большему накоплению жировой ткани в организме и усиливает развивающиеся на фоне ожирения метаболические нарушения [9,10].…”