Integrative Proteomic and Phosphoproteomic Profiling of Testis from Wip1 Phosphatase-Knockout Mice: Insights into Mechanisms of Reduced Fertility**

Abstract

Wei et al. apply multi-layer proteomic profiling and systems biology approaches to define Wip1-deficient testis proteome and phosphoproteome landscapes, and they identify cell adhesion/tight junction, sperm motility, and inflammatory response pathways. These data establish the mechanism that proinflammatory cytokines may impair the blood-testis barrier dynamics by decreasing the expression of junction-associated proteins in Wip1 null testes, leading to subfertility and spermatogenesis defects.

Ablation of the canonical testosterone production pathway via knockout of the steroidogenic enzyme HSD17B3, reveals a novel mechanism of testicular testosterone production

“…Our data also highlight Hsd17b12 as a possible candidate for basal testosterone production in the fetal and/or adult testis, as it is expressed in the testis throughout life, and transcript levels are significantly increased in Hsd17b3 −/− adult males. HSD7B12 in humans is present in Leydig cells and Sertoli cells 34 and in “Human protein atlas” (http://www.proteinatlas.org) 35 and has been identified in the proteome of whole adult mouse testis 26,36 and our own immunohistochemical analysis localizes HSD17B12 to Leydig cells and faintly in the germ cells in control and Hsd17b3 −/− testes. However, while Hsd17b12 is able to convert androstenedione to testosterone in mice, 37 its steroidogenic activity is largely restricted to estrone reduction to estradiol in humans, with low levels of androstenedione reduction 25,31 .…”

miR-122-5p regulates the tight junction of the blood-testis barrier of mice via occludin

“…TJs are the major component of the BTB [ 16 ], and abnormal TJs affect spermatogenesis [ 19 , 33 ]. Our previous study indicated that the expression of miR-122-5p correlated with spermatogenesis.…”

Male Fertility Potential Molecular Mechanisms Revealed by iTRAQ-Based Quantitative Proteomic Analysis of the Epididymis from Wip1−/− Mice

“…Our previous study reported that inflammatory response proteins can impair the integrity of blood-testis barrier by downregulating the junction proteins in Wip1-null testis, resulting in abnormal spermatogenesis (Wei et al, 2018). Therefore, this result may reflect that elevated inflammatory level was associated with abnormal sperm morphology and decreased number in the epididymis.…”