Homeobox (HOX) genes encode proteins that are important in normal foetal development. Some of these genes such as HOXA10 also appear to be involved in haematopoiesis, tumour invasion and normal uterine function. HOXA10 is sensitively regulated by hormonal changes during the menstrual cycle. In addition, knockout mouse studies have suggested a role for HOXA10 in implantation but its precise mechanism of action remains unclear. To further investigate HOXA10 function in human reproduction we have assessed changes in mRNA expression across gestation and following hormone treatment of in vitro models. Quantitative RT-PCR was used to assess changes in mRNA expression for HOXA10 (relative to 18S rRNA) in decidua and placenta at different gestations: 1st trimester (mean 8.1 wks) (n=31 placenta, n=8 decidua); 2nd trimester (13.7 wks) (n=12 placenta, n=7 decidua) and 3rd trimester (39.3 wks) (n=12 placenta, n=11 placenta). HOXA10 expression was higher in decidua (1st = 3.5-fold, 2nd = 2-fold, 3rd = 31-fold relative to 1st trimester placenta) compared with placenta (2nd = 0.3-fold, 3rd = 12-fold relative to 1st trimester placenta). Placentae from fetuses with intrauterine growth restriction (gestational age 29.4 wks) showed no significant variation in HOXA10 mRNA levels compared with normal 3rd trimester samples. Studies in vitro showed that endometrial Ishikawa cells were strongly positive for HOXA10 (1000-fold relative to 1st trimester placenta) with expression being stimulated primarily by the known HOXA10 regulator, 1,25-dihydroxyvitamin D (100 nM, 24 and 48 hrs). In contrast, trophoblastic JEG-3 cells showed no basal or induced expression. These data indicate that HOXA10 is regulated in a biphasic fashion across gestation, paralleling changes in progesterone levels. We therefore postulate that, in addition to its established role in implantation, HOXA10 may have important novel functions in late gestation.
08 - 11 Apr 2002
British Endocrine Societies