Mechanisms of OCT4 on 3,5,3’-Tri-iodothyronine and FSH-induced Granulosa Cell Development in Female Mice

Abstract

Octamer-binding transcription factor 4 (OCT4) regulates the pluripotency of stem cells and also plays important roles in granulosa cells growth, which is regulated by follicle-stimulating hormone (FSH). Thyroid hormone (TH) is important for the development and maturation of follicles and the maintenance of various endocrine functions. Although 3,5,3′-triiodothyronine (T3) enhances the effects of FSH on the regulation of the growth of granulosa cells and development of follicles, it is unclear whether and how TH combines with FSH to regulate OCT4 expression in granulosa cells during the preantral to early antral transition stage. Our results showed that T3 enhanced FSH-induced OCT4 expression. However, T3/FSH-induced cellular growth was reduced by OCT4 siRNA. OCT4 knockdown significantly increased the number of apoptotic cell. Moreover, T3 combined with FSH to increase ERβ expression, but did not significantly affect ERα expression. ERβ knockdown dramatically decreased T3/FSH-induced OCT4 expression and cell development and increased cell apoptosis. The PI3K/Akt pathway was involved in hormones inducing OCT4 and ERβ expressions. Furthermore, the hormones regulating OCT4 and ERβ expressions were regulated by cytochrome P450 lanosterol 14a-demethylase (CYP51), a key enzyme in sterol and steroid biosynthesis. T3 and FSH cotreatment potentiated cellular development by upregulating OCT4 expression, which is mediated by CYP51 and ERβ. These regulatory processes are mediated by the PI3K/Akt signaling pathway. These findings suggest that OCT4 mediates the T3 and FSH-induced development of follicles.

Effects of omega-3 polyunsaturated fatty acids on cellular development in human ovarian granulosa tumor cells (KGN)

“…And OCT4 not only promotes the formation of stem cells and germ cells, but also increases granulosa cell development (56). In our previous study, the expression of OCT4 is regulated by ERβ and CYP51, which are related to the synthesis and effects of estrogen (7). In the present study, omega-3 down-regulated OCT4 expression.…”

“…The hydrophilic molecule glucose cannot permeate the cell membrane, and its utilization requires the transport and catalysis of GLUTs, which is a protein family, including a variety of proteins, widely distributed in various tissues in the body (7,(30)(31)(32). In this study, we showed that omega-3 significantly down-regulated GLUT1 and GLUT4 proteins content.…”

“…Furthermore, estrogen may act through a homeodomain transcription factor, Octamer-binding transcription factor 4 (OCT4) known as a member of the Pit-Oct-Unc (POU) family of transcription factors. Our previous study showed that OCT4 is related to the granulosa cell growth, which is regulated by estrogen receptor β (ERβ) and P450 lanosterol 14a-demethylase (CYP51) (7).…”

Image analysis quantification of sperm acrosome associated 3 protein expression in domesticated and free‐roaming equine ovaries

“…Within the ovary, granulosa cells proliferate in the developing follicle during folliculogenesis and are regulated by a variety of factors (e.g. follicle stimulating hormone, thyroid hormone, oestrogen, octamer binding transcription factor 4 [OCT4]; Wang et al, 2021;Yada et al, 1999).…”

Activin A Reduces Porcine Granulosa Cells Apoptosis via ERβ-Dependent ROS Modulation

“…The accelerated metabolic rates and the cumulative accumulation of the reactive oxygen species (ROS) are linked to higher demands for energy and nutrients throughout the reproductive process. Unfavorable environmental conditions, such as bacterial infection and heat stress, are well known to promote the accumulation of ROS [22,37]. Although ROS are by-products of aerobic metabolism that are naturally occurring, the excessive ROS production causes oxidative stress and cellular damage.…”