Comparison of steroid hormones in three different preeclamptic models

Abstract

Preeclampsia (PE) is a complication of pregnancy and is characterized by hypertension and proteinuria, threatening both the mother and the fetus. However, the etiology of PE has not yet been fully understood. Since the imbalance of steroid hormones is associated with the pathogenesis of PE, investigating steroidogenic mechanisms under various PE conditions is essential to understand the entire spectrum of pregnancy disorders. Therefore, the current study established three PE in vitro and in vivo models, and compared the levels of steroid hormones and steroidogenic enzymes within them. In cellular PE models induced by hypoxia, N-nitro-L-arginine methyl ester hydrocholride (L-NAME) and catechol-o-methyltransferase inhibitor, the levels of steroid hormones, including pregnenolone (P5), progesterone (P4), dehydroepiandrosterone (DHEA) and testosterone tended to decrease during steroidogenesis. Injection of L-NAME in pregnant rats led to a reduction in the levels of estradiol and P4 through regulation of cholesterol side-chain cleavage enzyme (CYP11A1) and 3β-hydroxysteroid dehydrogenase/δ5 4-isomerase type 1 (HSD3B1), whereas rats treated with COMT-I exhibited elevated levels of P5 and DHEA by regulation of the CYP11A1 and aromatase cytochrome P450 (CYP19A1) in the placenta and plasma. The reduced uterine perfusion pressure operation decreased CYP11A1 and increased CYP19A1 expression in placental tissues, whereas steroid hormone levels were not altered. In conclusion, the results of the present study suggest that the induction of PE conditions dysregulates the steroid hormones via regulation of steroidogenic enzymes, depending on specific PE symptoms. These findings can contribute to the development of novel diagnostic and therapeutic modalities for PE, by monitoring and supplying appropriate levels of steroid hormones.

Expression of Key Steroidogenic Enzymes in Human Placenta and Associated Adverse Pregnancy Outcomes

“…A study using next-generation sequencing to detect dysfunctional blastocysts found that decreased expression of CYP11A1 was a cause of embryo implantation failure 17 . Meanwhile, CYP11A1 expression level was significantly higher in PE compared with normal placenta of humans and rats, which is in line with the observed increase in PREG level 18,24 . CYP11A1 overexpression suppressed trophoblast proliferation and induced HTR8/SVneo cell apoptosis by activating caspase-3.…”

“…17 Meanwhile, CYP11A1 expression level was significantly higher in PE compared with normal placenta of humans and rats, which is in line with the observed increase in PREG level. 18,24 CYP11A1 overexpression suppressed trophoblast proliferation and induced HTR8/ SVneo cell apoptosis by activating caspase-3. Similarly, increased placental CYP11A1 expression resulted in the production of lipid peroxides, which may contribute to the pathogenesis of PE.…”

Upregulation of ENDOU in cytotrophoblasts from placenta complicated with preeclampsia and fetal growth restriction

“…ALPP, CYP19A1, and FSTL3 were excluded from further analysis as they have been previously reported to be associated with the pathology of PE or FGR. (13)(14)(15)(16)(17)…”

“…( 11 ) Microarray analysis has shown that ENDOU mRNA is significantly increased in cytotrophoblasts isolated from PE placentas. ( 12 ) Of these proteins, ALPP, ( 15 ) CYP19A1, ( 14 , 16 ) and FSTL3 ( 13 , 17 ) have already been reported to be associated with the pathology of PE; thus, they were excluded from further investigation. In the present study, the expression levels of APOA1, ENDOU, and MTPN were evaluated in PE-FGR placentas by immunohistochemistry.…”

Progesterone Induces Apoptosis and Steroidogenesis in Porcine Placental Trophoblasts

“…As pregnancy progresses, the placenta becomes the principal source of steroid hormone synthesis [ 8 , 32 ]. An imbalance of steroid hormones is related to many pregnancy complications, such as preeclampsia, caused by insufficient P4 [ 69 ]. A premature increase in P4 levels is related to abnormal implantation and decreased pregnancy rates [ 70 , 71 , 72 , 73 ].…”