Revisiting Steroidogenic Pathways in the Human Placenta and Primary Human Trophoblast Cells

Abstract

Steroid hormones play a crucial role in supporting a successful pregnancy and ensuring proper fetal development. The placenta is one of the principal tissues in steroid production and metabolism, expressing a vast range of steroidogenic enzymes. Nevertheless, a comprehensive characterization of steroidogenic pathways in the human placenta and potential developmental changes occurring during gestation are poorly understood. Furthermore, the specific contribution of trophoblast cells in steroid release is largely unknown. Thus, this study aimed to (i) identify gestational age-dependent changes in the gene expression of key steroidogenic enzymes and (ii) explore the role of trophoblast cells in steroid biosynthesis and metabolism. Quantitative and Droplet Digital PCR analysis of 12 selected enzymes was carried out in the first trimester (n = 13) and term (n = 20) human placentas. Primary trophoblast cells (n = 5) isolated from human term placentas and choriocarcinoma-derived cell lines (BeWo, BeWo b30 clone, and JEG-3) were further screened for gene expression of enzymes involved in placental synthesis/metabolism of steroids. Finally, de novo steroid synthesis by primary human trophoblasts was evaluated, highlighting the functional activity of steroidogenic enzymes in these cells. Collectively, we provide insights into the expression patterns of steroidogenic enzymes as a function of gestational age and delineate the cellular origin of steroidogenesis in the human placenta.

Altered Steroidome in Women with Gestational Diabetes Mellitus: Focus on Neuroactive and Immunomodulatory Steroids from the 24th Week of Pregnancy to Labor

“…However, it readily metabolizes Δ 5 and Δ 4 steroids. Since none of the Δ 5 or Δ 4 steroids in cord blood showed significant differences between the GDM+ and GDM− groups ( Table S2 ), the differences in the 5α/β-reduced metabolites of 17-hydroxyprogesterone and one 5α-reduced androgen may be considered as a sign of reduced activity of maternal and/or placental CYP17A1 in GDM+ group (see [ 51 ]).…”

“…A trend towards lower levels of 16α-hydroxyprogesterone and 20α-dihydroprogesterone was also observed in the GDM+ group at labor ( Table 1 ). In addition to its diabetogenic effects, progesterone as cortisol triggers immunoregulatory signals in T cells (see [ 51 ]).…”

“…Moreover, these more stable reduced catabolites appear to be better indicators of the CYP17A1 activities than the Δ 4 and Δ 5 steroids. The functional activity of the “backdoor pathway” in placenta was recently hypothesized by Karahoda et al [ 51 ].…”

“…The isoforms of SRD5As are expressed in numerous tissues including placenta [ 71 , 72 ]. Relative to tissue weight, the human placenta expresses SRD5A1 around 1000 times more than the testis (see [ 51 ]). The highest extraplacental expression of the SRD5A1 isoform has been reported in the fetal brain [ 72 ], which is likely related to increased fetal brain demands for synthesis of the neuroprotective GABAergic steroid allopregnanolone [ 70 ].…”

Investigation of the effect of steroidal imidazoheterocycles hormone derivatives on JEG-3 trophoblast cells of choriocarcinoma

“…The placenta is one of the main tissues that synthesize steroid hormones and affect the normal maintenance of pregnancy and fetal development (KARAHODA et al, 2021). Investigations of the mechanisms of synthesis, metabolism and secretion of steroid hormones are very important because disturbance of steroid hormones during pregnancy can lead to various disorders.…”