Table 4.
The panel of potential SV biomarkers for estrogenic exposure with their recognized E2-associated functions.
| Gene | Protein | Fold Change Upon E2 Exposure | p * | Function |
|---|---|---|---|---|
| NGAL/LCN2 | Neutrophil gelatinase-associated lipocalin | 18 | 0.01 | Acute inflammation marker [33]. Potential marker for acute kidney injury and metabolic disorders [34,35]. |
| GLUL | Glutamine synthetase | 12 | 0.011 | Mediates the synthesis of glutamine [36]. Expression is tied to estrogen receptors in glial cells [37]. |
| PIGR | Polymeric immunoglobulin receptor | 9.5 | 0.032 | Transmembrane transporter found on mucosal surfaces. Transports IgA and IgM. Maintains mucosal immune functions [38]. Increased expression in males with varicoceles, a condition which may lead to male infertility [39]. |
| SPON1 | Spondin-1 | 8.3 | 0.001 | mRNA expression was found in various tissues. However, protein expression was not detected [40]. Function unknown in the male reproductive system [41]. |
| SVS5 | Seminal vesicle secretory protein 5 | 7.5 | 0.016 | Processed by prostate-specific antigen, involved in promoting sperm motility. Elevated levels may promote male infertility [42]. |
| AGT | Angiotensinogen | 6.5 | 0.016 | Involved in the regulation of the renin-angiotensin system [43]. Seminal AGT may be involved in regulating sperm motility [44]. |
| S100A11 | Protein S100-A11 | −2 | 0.045 | Calcium-binding protein is involved in various regulatory functions [45]. Considered a marker for inflammation. Upregulated in colon and prostate cancers [46,47]. |
| PTGES3 | Prostaglandin E synthase 3 | −2.5 | 0.028 | Promotes the function of steroid receptors in the immune system, and mRNA expression may be reduced after exposure to bisphenol A [48,49]. |
| DCXR | L-Xylulose reductase | −2.5 | 0.004 | Short-chain reductase metabolizes xylulose, quinone, and diacetyl with other potentially unknown functions [50]. Sperm surface protein, essential for gamete fusion and fertilization, is reduced in patients with SCI-induced male infertility [51,52]. |
| CBX1 | Chromobox protein homolog 1 | −3.3 | 0.014 | Androgen receptor cofactor and regulates the androgen receptor’s genomic activity. Upregulated in castration-resistant prostate cancer [30]. |
| NENF | Neudesin | −5 | 0.008 | Function in the male reproductive system has yet to be fully elucidated. Expression at the mRNA level may be reduced after ER activation but is cell-specific [53]. |
| PGM-1 | Phosphoglucomutase-1 | −5 | 0.006 | Involved in glycogen metabolism and N-glycosylation. Reduced expression in patients who have SCI-induced infertility [52,54]. |
* Post hoc t-test: E2-treated versus control.