Table 1.
Summary of creatine metabolism in the female reproductive tract.
| Tissue | Species | Creatine and Phosphocreatine Content | Creatine Kinases | Creatine Synthesis and Transport |
|---|---|---|---|---|
| Oocytes | Mouse | Creatine and phosphocreatine present (~4 to 5 mmol.kg−1 dry mass) [16]. | CKBB gene, protein and activity reported [16,17]. Activity increased with oocyte maturation and fertilization [18]. CKMM detected. Expression levels increased with hCG stimulation [9]. |
|
| Bovine | uMt-CK and CKBB gene and protein expression reported [18]. Use of CK inhibitors elevated intra-oocyte ADP:ATP ratio [19]. | |||
| Human | Creatine and phosphocreatine present (~4 to 5 mmol.kg−1 dry mass) [16]. | |||
| Ovaries | Rat | High SLC6A8 gene expression reported [21]. | ||
| Ovarian stromal cells | Human | Detectable levels of the GATM gene and AGAT protein, but GAMT undetected [22]. | ||
| Cumulus cells or cumulus–oocyte complexes (COCs) | Human | CKBB gene expression detected and elevated in women with good quality embryos undergoing ART [23]. | ||
| Bovine | Creatine and GAA detected in media bathing cells, with an increase in creatine (~450-fold) and GAA (~2-fold) reported during in vitro maturation [24]. | |||
| Follicular fluid | Human | Creatine detected and lower in women with endometrioma [30]. | ||
| Mouse | Creatine detected and increases around ovulation [9]. | |||
| Equine | Creatine detected. Remains unchanged with follicular development [31]. | |||
| Granulosa cells | Rat | Increase in GATM and GAMT expression with equine CG stimulation [9]. | ||
| Oviduct | Human | GATM and GAMT and SLC6A8 detected [21,22] | ||
| Rat | GATM and GAMT and SLC6A8 detected [21,22] | |||
| Mouse | GAMT gene and protein not expressed [32] | |||
| Oviductal fluid | Equine | High creatine concentration (3–4 mM) that did not change pre- to post-ovulation [33,34]. | ||
| Mouse | Creatine levels detected and increased with hCG stimulation [9]. | GATM and GAMT detected. No change in expression with hCG stimulation [9]. | ||
| Non-pregnant Endometrium | Human | Up-regulation of CKBB expression and enzyme activity in the secretory phase of the menstrual cycle [37,39,40,41]. | Increased SLC6A8 expression during the secretory phase of the menstrual cycle [37]. | |
| Pregnant endometrium | Rat | uMt-CK and CKBB proteins expressed in the decidua parietalis and basalis [36]. | AGAT activity high in the decidua. No GAMT enzyme activity present [48]. | |
| Sheep | GAA produced at a higher level than non-pregnant animals [49]. | |||
| Human | Creatine kinase activity present in term decidual explants [46]. | |||
| Non-pregnant myometrium | Human | Phosphocreatine detected at a low level compared pregnant myometrium [51]. | Creatine kinase activity detected [50]. | |
| Pregnant myometrium | Human | Phosphocreatine detected with higher levels at term compared to non-pregnant tissue [55]. | CKBB gene expression detected. Levels were three-fold higher at term compared with earlier in gestation [53]. |
Abbreviations—cytosolic brain-type creatine kinase (CKBB), cytosolic muscle-type creatine kinase (CKMM), ubiquitous mitochondrial creatine (uMt-CK), guanidinoacetate (GAA), artificial reproductive therapy (ART), human chorionic gonadotropin (hCG), chorionic gonadotropin (CG).