Aromatase, oestrogens and human male reproduction

Abstract

In most mammalian species aromatase is encoded by a single gene (Cyp19), which contains 18 exons, nine of them being translated. In man, the presence of a biologically active aromatase and oestrogen receptors (ERa and ERb) has been reported in Leydig cells, and also in immature germ cells and ejaculated spermatozoa. Concerning aromatase, the amount of transcript and enzymatic activity are decreased in immotile compared with motile sperm. We have amplified aromatase mRNA by real-time polymerase chain reaction in spermatozoa from asthenospermic, teratospermic and asthenoteratospermic men and recorded, respectively, 44, 52 and 67 per cent decreases of the amount of transcripts compared with fertile donors. A high degree of correlation (r ¼ 20.64) between the abnormal spermatozoa (especially microcephaly and acrosome malformations) and aromatase/GAPDH transcript ratio has been observed. Idiopathic infertility is a wide health problem and no treatment is currently available. In humans, even if the role of oestrogens in spermatogenesis is still a matter of debate, the observations of decreased sperm number and motility in men genetically deficient in aromatase, together with our data and those reported in the literature, may suggest a role for aromatase/oestrogens not only during the development and maintenance of spermatogenesis but also in the final maturation of spermatozoa.

Estrogen receptor alpha localization in the testes of men with normal spermatogenesis

“…The inconsistency of the reports on ERa localization in the human testis (for a review, see [27,28]) may be due to the lack of homogeneity of the examined groups, i.e. different abnormalities in spermatogenesis.…”

Actin-binding protein drebrin E is involved in junction dynamics during spermatogenesis

“…[1][2][3][4][5][6][7][8][9][10] In the seminiferous tubules, a unique ultrastructure known as the blood-testis barrier (BTB), which is created by coexisting tight junctions (TJ), basal ectoplasmic specializations (basal ES), desmosomes and the actin-based cytoskeleton plays a critical role in the seminiferous epithelium during spermatogenesis by conferring cell shape, adhesion, structural support and cell polarity to both Sertoli and developing germ cells, which are essential for spermatogonial stem cell renewal, maintenance of the stem cell niche, cell cycle progression, mitosis, meiosis, spermiogenesis and spermiation. However, few functional studies are found in the literature, which explore the functional significance of actin dynamics in these events.…”

Teasing out the role of aromatase in the healthy and diseased testis

“…1). 2 This balance is governed by cytochrome P450 aromatase, which when complexed with NADPH-cytochrome P450 reductase, catalyzes the irreversible conversion of C 19 androgenic steroid substrates, testosterone and androstenedione, into the C 18 estrogens, estradiol and estrone, within the endoplasmic reticulum (reviewed in ref.…”

“…43,44 However, there is a degree of uncertainty as to the precise location of aromatase in spermatozoa, with studies claiming it is solely restricted to the flagellum, 44 that it's present in both the flagellum and head 45 and that it occupies numerous sites stretching the entire length of the spermatozoon (reviewed in ref. 1). The role of aromatase in spermatozoa is thought to be in regulating sperm motility, as it has been noted that immobile human spermatozoa contain markedly reduced levels of aromatase activity compared with their mobile counterparts, 43 whether this can be attributed to changes in mitochondrial function is worth consideration.…”