Environmental mixture with estrogenic activity increases Hsd3b1 expression through estrogen receptors in immature rat granulosa cells

Abstract

Humans are exposed not only to single endocrine disruptors, but also to chemical mixtures that can adversely affect their reproductive health. Steroidogenesis in reproductive tissues is emerging as the key target of endocrine disruptor action. Here, we analyzed the effect of environmental chemical mixtures with estrogenic activity on steroidogenic processes in immature rat granulosa cells and whether the observed steroidogenic effects were mediated through estrogen receptors. Extracts from untreated wastewater were prepared by solid-phase extraction and silica gel fractionation. ER-CALUX assay showed that the polar fractions of wastewater exerted different levels of estrogenic activity. Exposure of immature granulosa cells to the polar fraction exerting 9 ng of 17β-estradiol equivalents per liter of water of estrogenic activity increased mRNA expression of the key enzymes of progesterone biosynthetic pathway Star and Hsd3b1, but did not alter the level of Cyp19a1 and Lhr. Addition of estrogen receptor inhibitor ICI 182 780 prevented the estrogenic mixture-induced increase in Hsd3b1, but not Star mRNA level in immature granulosa cells. These results indicate that the environmental chemical mixtures with estrogenic activity exert endocrine disrupting effects by augmenting the progesterone biosynthetic pathway in immature rat granulosa cells, which is an effect achieved in part through activation of the estrogen receptors.

Efficacy of Immunization against a Novel Synthetic 13-Amino Acid Betaglycan-Binding Peptide Sequence of Inhibin α Subunit on Promoting Fertility in Female Rats

“…In parallel to enhanced folliculogenesis, we found that the expressions of key genes associated with both follicle development ( Creb , Ccnd2 and Inhα ) and estrogen biosynthesis ( Cyp11a1 , HSD3b1 and Cyp19a1 ) in ovaries were all significantly upregulated in rats following INHα13AA-T immunization. Of these, except for HSD3b1 in granulosa cells being directly regulated by FSH [ 28 ], the other genes were all directly FSH downstream genes [ 29 , 30 ]. In contrast, the LH target ovarian steroidogenic genes ( Star [ 31 ] and Cyp17a1 [ 32 ]), as well as pituitary Lhb expression and serum LH concentrations, were all unchanged, as was reported elsewhere [ 11 , 12 , 15 , 19 , 20 , 21 , 22 ].…”

New Gene Markers of Exosomal Regulation Are Involved in Porcine Granulosa Cell Adhesion, Migration, and Proliferation

“…This indicates that the genes of interest may be crucial for steroidogenesis in porcine granulosa cells. Upregulated 3β-hydroxysteroid dehydrogenase 1 (HSD3B1) plays an important role in steroidogenesis [62]; its expression is dependent on imidacloprid [62] and estrogen [63].…”

REPRODUCTIVE TOXICOLOGY: Effects of chemical mixtures on the ovary

“…The mixture-induced decrease in estradiol corresponds to upregulation of Cyp1a1, an enzyme that metabolizes estradiol (Meling et al 2020). A mixture of estrogenic extracts isolated from untreated wastewater increased expression of the steroidogenic factors Star and Hsd3B1 in cultured mouse granulosa cells (Samardzija Nenadov et al 2018). This effect was likely mediated through activation of estrogen receptors (Samardzija Nenadov et al 2018).…”

“…A mixture of estrogenic extracts isolated from untreated wastewater increased expression of the steroidogenic factors Star and Hsd3B1 in cultured mouse granulosa cells (Samardzija Nenadov et al 2018). This effect was likely mediated through activation of estrogen receptors (Samardzija Nenadov et al 2018). In other studies, a PBDE mixture (PBDE 47, 99, 100, and 209) was applied to co-cultured theca and granulosa cells in low (0.5; 0.25; 0.1; 0.05 ng/ mL), medium (25; 10; 4.0; 0.25 ng/mL), and high (50; 17.5; 12.5; 0.5 ng/mL) doses in short term and longterm culture periods.…”