This study has shown that the mouse has a great increase in
steroid production during pregnancy in similar fashion to the human. Many
steroids were provisionally identified in maternal urine of the wild-type mouse. The major
progesterone metabolites appear to be hydroxylated pregnanolones, particularly with
hydroxyl groups in the 16alpha position. Rather than
estriol being the major end-product of feto-placental
steroid synthesis as in the human, the pregnant mouse produces and excretes large amounts of
androgen metabolites, ranging in polarity from androstanetriols to androstanepentols. These
steroids have 15alpha- or 18-hydroxyl groups with additional hydroxylation at uncharacterized positions. From metabolite data the peak of pregnancy
progesterone production appears to be between 7.5 and 14.5 gestational days, while for C(19) metabolites peak excretion is later. The starting-point of the studies was to study pregnancy
steroid production by a mouse model for
Smith-Lemli-Opitz syndrome, 7-dehydrosterol
reductase (DHCR7) deficiency. In human pregnancies with DHCR7 deficient fetuses large amounts of 7- and 8-dehydrosteroids are excreted, products secondary to high fetal 7- and
8-dehydrocholesterol (DHC) accumulation. This agrees with existing evidence that human feto-placental
steroid synthesis utilizes little maternal
cholesterol as precursor. In contrast, this study has shown that pregnant mice carrying dhcr7 deficient fetuses with relatively high DHC production had essentially undetectable maternal excretions of
steroids with Delta(7)- and Delta(8)-unsaturation. As mutant mouse mothers have essentially normal
cholesterol production (little or no DHC build-up), this suggests maternal
cholesterol is primarily utilized for pregnancy
steroid synthesis in the mouse.