Table 1.
Gene ontology grouping of the differentially expressed genes in response to 17β-estradiol
| Molecular Function | Gene Name | Fold Change | *Localization in the Testis | Function | Ref. |
|---|---|---|---|---|---|
| I) Metabolism (androgen and xenobiotic) | 1) Steroidogenic acute regulatory protein (Star) | -5.45 | Leydig cells, Sertoli cells | Carrier protein involved in transport of cholesterol to the inner mitochondrial membrane | [53] |
| 2) Hydroxysteroid 11-beta dehydrogenase-1(Hsd11b1) | -2.10 | Interstitial cells | Androgen & estrogen metabolism | [54] | |
| 3) Alcohol dehydrogenase-1 (Adh1) | -3.28 | Leydig and Sertoli cells | Enzyme catalyzing the rate limiting step in the conversion of retinol to retinoic acid | [28] | |
| 4) Carboxylesterase-3 (Ces3) |
-26.85 | Leydig cells | Synthesis of testosterone; protects Leydig cells from damage by toxins | [26] | |
| 5) Cytochrome P450, family-1, subfamily-b, polypeptide-1 (Cyp1b1) | -2.41 | Leydig cells | Involved in xenobiotic metabolism | [27] | |
| 6) Sulfotransferase family 1A, phenol-preferring, member-1 (Sult1a1) | -2.12 | Leydig cells | Involved in xenobiotic metabolism | [55] | |
| II) Cytoskeletal maintenance | 1) Actin related protein 2/3 complex, subunit-1B (Arc 1B or p41Arc) Actin related protein 2/3 complex, subunit-5-like (predicted) (Arpc5L) |
-2.46 -2.01 |
Sertoli cells | Part of the Arp2/3 complex; contributes to the stability of the complex and are involved in the de novo polymerization of actin | [31,32] |
| 2) ENA Vasodilator Phosphoprotein (Evl) | -2.12 | Germ cells* | Actin binding protein involved in actin dynamics | [56] | |
| 3) Capping protein gelsolin like (Capg) | -2.42 | Ectoplasmic specialization | An actin severing protein | [33] | |
| 4) Tubulin beta-5 (tubb5) | -2.22 | Sertoli and germ cells* | Component of microtubules which is responsible for spermatid translocation in the mammalian seminiferous epithelium |
[57] | |
| 5) dynein cytoplasmic light intermediate polypeptide (Dncli2) | -2.29 | Sertoli and germ cells* | Component of dynein, the motor protein, responsible for spermatid translocation in the mammalian seminiferous epithelium and Sertoli cell protein transport |
[57] | |
| 6) casein kinase-2 beta subunit (Csnk2b) | -2.34 | Sertoli and germ cells* | Disruption of Csnk2a results in infertility, globozoospermia and retention of defective spermatids | [35] | |
| III) Intracellular transport and endocytosis | 1) Syntaxin-5a (Stx5a) | -2.22 | Sertoli cells* | Involved in Golgi function, cytokinesis, and spermatid differentiation in drosophila | [58] |
| 2) Syntaxin -8 (Stx8) | -2.10 | Spermato-gonia and Sertoli cells* | Involved in vesicular transport and membrane fusion events necessary for protein transport from early endosomes to late endosomes. |
[59] | |
| 3) Adaptor-related protein complex-2, sigma-1- subunit (Ap2S1) | -2.07 | Sertoli and germ cells* | Ap2S1 gene codes for the sigma subunit of the AP2 complex and helps in targeting of the complex to membranes. AP2 complex is known to trigger the formation of the clathrin lattice machinery at the plasma membrane | [37] | |
| 4) Ral A binding protein (Ralbp1) | -2.06 | Spermato-gonia & Sertoli cells* | RalBP1 is a putative effector protein of Ral and possesses the GTPase-activating activity for Rac1 and CDC42 is a critical component of clathrin-coated pit-mediated endocytosis | [60] | |
| 5) trafficking protein particle complex 1 (predicted) (Trappc1) | -2.01 | Sertoli and germ cells* | Multisubunit tethering complex involved in vesicle mediated transport | [61] | |
| 6) Lysosomal membrane glycoprotein-2 (Lamp 2) | -2.00 | Tubulobulbar complexes | Lamp 1 and 2 are involved in lysosome biogenesis, autophagy, and cholesterol homeostasis. Lamp 1 is speculated to be involved in endocytosis and internalization of junctions | [39,40] | |
| 7) Phosphatidylinositol binding clathrin assembly protein (PiCalm) | +2.41 | Germ cells and very little expression in Sertoli cells* | Homologue of the AP180 protein, it plays a significant role in the clathrin internalization machinery and over expression of the protein destabilizes the clathrin complex thus disrupting clathrin mediated endocytosis |
[38] | |
| IV) Iron metabolism | 1) Haptoglobin (Hp) | 9.25 | Leydig cells, Sertoli cells and germ cells | Hp protein is speculated to be involved in the recycling of heme groups hence involved in the maintenance of Sertoli cell function | [43] |
| 2) Hemoglobin alpha adult chain-1 (Hba-a1) and beta chain complex (Hbb). | -8.85 -9.89 |
Spermato-gonia* | Possible influence on germ cell number | [44] | |
| 3) Solute carrier family-39 (iron-regulated transporter), member-1 (Slc40a1) | +2.21 | Round spermatids and Sertoli cells* | Basolateral iron transporter family | [45] | |
| (V) Germ cell apoptosis | 1) Nitric oxide synthase-3, endothelial cell (Nos3) | +4.02 | Degenerating germ cells | Calcium dependant enzymes which probably has a role in apoptosis | [47,48] |
| 2) Retinoblastoma- 1 (Rb1) | +2.73 | Sertoli cells and spermato-gonia* | Regulates G1/S transition in cell cycle | [62] | |
| 3)Transforming growth factor beta receptor-3 (Tgfbr3) | +2.17 | All testicular cell types | Transmission of extracellular TGF signal into the cell and induce apoptosis in gonocytes of fetal testis in vitro to control germ cell numbers during fetal life | [49,50] | |
| 4) Peroxiredoxin-3 and -6 (Prdx3 and Prdx6) | -2.81 -2.73 |
Spermato-gonia and spermato-cytes with maximal expression in pachytene spermato-cytes | Oxidative stress related proteins which are cytoprotective and know to maintain mitochondrial integrity; decrease in Prdx3 is known to sensitize cells to apoptotic stimulus | [52,63] |
'*' Testicular localization of most of the genes listed in the table was obtained from the Mammalian Reproductive Genetics database [44].