Assisted reproduction technologies alter steroid delivery to the mouse fetus during pregnancy

Assisted reproduction technologies (ART) include in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI), and are common treatments for infertility. Although generally successful, ART warrant further investigations due to emerging perinatal issues, especially low birth weight. Herein we extend our previous work demonstrating higher steroid clearance in murine ART placentas by examining steroid biosynthesis and the directional flow of steroids in the maternal-placental-fetal units. The activities of the major steroidogenic enzymes 3β-hydroxysteroid dehydrogenase (3β-HSD) and cytochrome P450 17-αhydroxylase (CYP17) were assessed in maternal liver and ovaries and fetal livers as were levels of cholesterol, progesterone, estrone (E1), and estradiol (E2) in the maternal, placental and fetal units. No structural abnormalities were found in placentas from ART. Although ART increased 3β-HSD activity in maternal livers, there were no other changes in 3β-HSD- or CYP17-mediated steroidogenesis. Cholesterol levels were significantly lower in maternal livers of ICSI pregnancies and in placentas from both IVF and ICSI pregnancies but not altered in the fetal livers. Progesterone levels were higher in maternal and fetal livers in IVF and ICSI, respectively, but were significantly lowered in ICSI placentas, compared to normal fertilization. For estrogenic hormones, no differences in E1 or E2 levels were observed in maternal livers but ICSI significantly increased both E1 and E2 levels in placentas while both IVF and ICSI significantly lowered E1 but raised E2 levels in fetal livers. In summary, while steroid production was normal, steroid diffusion/flow from mother to fetus was altered in murine pregnancies conceived by ART. This appears to occur, at least in part; through placental mechanisms. Impaired cholesterol and steroid transfer may affect correct regulation of fetal growth and development.