Human type 2 17 beta-hydroxysteroid dehydrogenase mRNA and protein distribution in placental villi at mid and term pregnancy.
BACKGROUND
During human pregnancy, the placental villi produces high amounts of estradiol. This steroid is secreted by the syncytium, which is directly in contact with maternal blood. Estradiol has to cross placental foetal vessels to reach foetal circulation. The enzyme 17beta-hydroxysteroid dehydrogenase type 2 (17beta-HSD2) was detected in placental endothelial cells of foetal vessels inside the villi. This enzyme catalyzes the conversion of estradiol to estrone, and of testosterone to androstenedione. It was proposed that estradiol level into foetal circulation could be regulated by 17beta-HSD2.


METHODS
We obtained placentas from 10 to 26 6/7 weeks of pregnancy from women undergoing voluntary termination of pregnancy, term placentas were collected after normal spontaneous vaginal deliveries. We quantified 17beta-HSD2 mRNA levels in mid-gestation and term human placenta by RT-QPCR. We produced a new anti-17beta-HSD2 antibody to study its spatio-temporal expression by immunohistochemistry. We also compared steroid levels (testosterone, estrone and estradiol) and 17beta-HSD2 mRNA and protein levels between term placenta and endometrium.


RESULTS
High 17beta-HSD2 mRNA and protein levels were found in both mid-gestation and term placentas. However, we showed that 17beta-HSD2 mRNA levels increase by 2.27 fold between mid-gestation and term. This period coincides with a transitional phase in the development of the villous vasculature. In mid-gestation placenta, high levels of 17beta-HSD2 were found in mesenchymal villi and immature intermediate villi, more precisely in endothelial cells of the stromal channel. At term, high levels of 17beta-HSD2 were found in the numerous sinusoidal capillaries of terminal villi. 17beta-HSD2 mRNA and protein levels in term placentas were respectively 25.4 fold and 30 to 60 fold higher than in the endometrium. Steroid levels were also significantly higher in term placenta than in the endometrium.


CONCLUSIONS
The spatial and temporal expression of 17beta-HSD2 in the placenta during pregnancy and the comparison of 17beta-HSD2 expression and steroid levels between placental villi and endometrium are compatible with a role in the modulation of active and inactive forms of estrogens. Our observations strongly support the hypothesis that 17beta-HSD2 acts as a barrier decreasing estradiol secretion rates in the foetal circulation.
Drolet
Renée
R
Ontogeny and Reproduction Unit, Centre Hospitalier Universitaire de Québec, Centre de recherche du CHUL, Canada. renee.drolet@crchul.ulaval.ca
Simard
Marc
M
Plante
Julie
J
Laberge
Philippe
P
Tremblay
Yves
Y
D015067:17-Hydroxysteroid Dehydrogenases / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D002824:Chorionic Villi / Q000201:enzymology* / Q000502:physiology; D004960:Estradiol Dehydrogenases; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D011247:Pregnancy; D011262:Pregnancy Trimester, Second / Q000235:genetics*; D011263:Pregnancy Trimester, Third / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics
D012333:RNA, Messenger; D015067:17-Hydroxysteroid Dehydrogenases; D004960:Estradiol Dehydrogenases; C523763:HSD17B2 protein, human