Fetal-placental aromatase diciency is a rare autosomal recessive disorder in which individuals cannot synthesize endogenous estrogens (Grumbach, 2011; Simpson, 2000). To recall, fetal adrenal DHA-S is converted in the placenta to androstenedione, but in cases of placental aromatase deiciency, androstenedione cannot be converted to estradiol. Rather, androgen metabolites of DHEA produced in the placenta, including androstenedione and some testosterone, are secreted into the maternal or fetal circulation, or both. This can cause virilization of the mother and the female fetus (Belgorosky, 2009; Harada, 1992; Shozu, 1991).
Trisomy 21-Down syndrome screening searches for abnormal levels ofhCG, alpha-fetoprotein, and other analytes (Chap. 14, p. 281). It was discovered that serum unconjugated estriol levels low in women with Down syndrome fetuses (Benn, 2002). The likely reason for this is inadequate formation of C19 steroids in the adrenal glands of these trisomic fetuses.
Fetal eythroblastosis in some cases of severe fetal D-antigen alloimmunization can lead to elevated maternal plasma estrogen levels. A suspected cause is the greater placental mass from hypertrophy, which can be seen with such fetal hemolytic anemia (Chap. 15, p. 300).
Glucocorticoid treatment can cause a striking reduction in placental estrogen formation. Glucocorticoids inhibit ACTH secretion from the maternal and fetal pituitary glands. This diminishes maternal and fetal adrenal secretion of the placental estrogen precursor DHEA-S.
With Addison disease, pregnant women show lower estrogen levels, principally estrone and estradiol levels (Baulieu, 1956). The fetal adrenal contribution to estriol synthesis, particularly in later pregnancy, is quantitatively much more important.
Maternal androgen-producing tumors can present the placenta with elevated androgen levels. Fortunately, placenta is extraordinary eicient in the aromatization of C19 steroids. For example, Edman and associates (1981) found that virtually all androstenedione entering the intervillous space is taken up by syncytiotrophoblast and converted to estradiol. None of this C19 steroid enters the fetus. Second, a female fetus is rarely virilized if there is a maternal androgen-secreting tumor. The placenta eiciently converts aromatizable C19 steroids, including testosterone, to estrogens, thus precluding transplacental passage. Indeed, virilized female fetuses of women with an androgenproducing tumor may be cases in which a nonaromatizable C19 steroid androgen is produced by the tumor-for example, 5a-dihydrotestosterone. Another explanation is that testosterone is produced very early in pregnancy in amounts that exceed the placental aromatase capacity at that time.
Complete hydatidiorm mole and gestational trophoblastic neoplasias lack a fetus and also a fetal adrenal source of C19 steroid precursors for trophoblast estrogen biosynthesis. Consequently, placental estrogen formation is limited to the use of C 19 steroids from the maternal plasma, and therefore estradiol is principally produced (MacDonald, 1964, 1966).
Abel MH: Prostanoids and menstruation. In Baird DT, Michie EA (eds):
Mechanisms of Menstrual Bleeding. New York, Raven, 2002