scholarly journals Effects of sex steroid receptor agonists and antagonists on the expression of the FOXL2 transcription factor and its target genes AMH and CYP19A1 in the neonatal porcine ovary

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Patrycja Witek ◽  
Natalia Marek ◽  
Małgorzata Grzesiak ◽  
Maria Słomczyńska ◽  
Katarzyna Knapczyk-Stwora

Abstract Recently, we have demonstrated that neonatal exposure to androgen and estrogen agonists or antagonists influenced the number of ovarian follicles in piglets. Since the FOXL2 transcription factor is required for proper ovarian follicle formation and activation, the objective of the study was to examine effects of exposure of the neonatal porcine ovary to testosterone propionate (TP; an androgen), flutamide (FLU; an antiandrogen), 4-tert-octylphenol (OP; compound with estrogenic activity), ICI 182,780 (ICI; an antiestrogen), and methoxychlor (MXC; compound with estrogenic, antiestrogenic and antiandrogenic properties) on FOXL2 expression and expression of its target genes, AMH and CYP19A1. Piglets were injected subcutaneously with TP, FLU, OP, ICI, MXC, or corn oil (control) between postnatal days 1 and 10 (n = 4/each group). Ovaries were excised from the 11-day-old piglets and the expression of FOXL2, AMH and CYP19A1 were examined using immunohistochemistry and/or real-time PCR and Western blot. FOXL2 was localized in stroma cells surrounding egg nests and in granulosa cells. TP, OP and MXC increased both FOXL2 and AMH mRNAs, while FLU and ICI decreased CYP19A1 mRNA. The increased FOXL2 protein abundance was found in all examined groups. In addition, TP, OP, ICI and MXC increased AMH protein abundance, while TP, FLU and OP decreased CYP19A1 protein abundance. In conclusion, neonatal exposure to sex steroid receptor agonists and antagonists increased FOXL2 expression at mRNA and/or protein levels and affected FOXL2 target genes in the ovaries of 11-day-old piglets. Therefore, it seems that impaired ovarian folliculogenesis induced by altered steroid milieu during the neonatal development period in pigs may, at least in part, involve FOXL2.

1998 ◽  
Vol 258 (1) ◽  
pp. 96-102 ◽  
Author(s):  
Jennifer M. Dias ◽  
Ning Fei Go ◽  
Charles P. Hart ◽  
Larry C. Mattheakis

2004 ◽  
Vol 16 (9) ◽  
pp. 279 ◽  
Author(s):  
D. L. Russell

Female infertility has been reported in two lines of mice with mutation of the Egr-1 gene. One underlying cause of this defect is deficient LH production by pituitary gonadotropes. However, Egr-1 is also acutely regulated by both FSH and LH in ovarian granulosa cells (1). A role for this transcription factor in regulating gonadotrophin responsive target genes and ovarian function is hypothesised. Indeed the LH-receptor is a proposed target of Egr-1 regulation, but this has not been investigated in detail in vivo and is difficult to reconcile with the pattern of Egr-1 expression. In this study, the role of Egr-1 within the ovarian follicle was investigated using exogenous gonadotropin replacement in Egr-1–/– mice . Adult Egr-1–/– female mice superovulated by sequential PMSG and hCG stimulation and mated with proven male breeders failed to produced offspring while 90% of heterozygous females got pregnant and produced litters (7.4 � 2.9 pups per litter) within 22 days of stimulation. Recovery of oocytes from oviducts of immature superovulated mice revealed a reduced ovulation rate in null females (6.3 � 3.8 oocytes) compared to their heterozygous (18.0 � 6.5) and WT (17.8 � 6.8) littermates. Gross morphology and histology of exogenously stimulated ovaries were indistinguishable from their heterozygous or WT counterparts. Surprisingly, no alteration was detectable in the mRNA expression of previously reported direct Egr-1 responsive genes, namely LH-receptor and membrane prostaglandin E synthase (mPGES). Nor were mRNA for two critical ovulatory genes with putative Egr-1 response elements, ADAMTS-1 or versican V1 altered. Temporal and spatial expression of genes involved in ovarian steroidogenesis, P450scc and Cyp17 and LH-receptor, were indistinguishable from normal littermates during exogenously controled follicular development. Combined observations of acute Egr-1 induction by gonadotropins, reduced ovulation and complete infertility suggest an important role for Egr-1 in ovarian function. However, genes identified as targets of Egr-1 regulation in other studies proved to be Egr-1 independent in this model. (1) Russell et al. (2003) Mol. Endo. 17, 520.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Samina Shabbir ◽  
Prerona Boruah ◽  
Lingli Xie ◽  
Muhammad Fakhar-e-Alam Kulyar ◽  
Mohsin Nawaz ◽  
...  

AbstractOvary development is an important determinant of the procreative capacity of female animals. Here, we performed genome-wide sequencing of long non-coding RNAs (lncRNAs) and mRNAs on ovaries of 1, 3 and 8 months old Hu sheep to assess their expression profiles and roles in ovarian development. We identified 37,309 lncRNAs, 45,404 messenger RNAs (mRNAs) and 330 novel micro RNAs (miRNAs) from the transcriptomic analysis. Six thousand, seven hundred and sixteen (6716) mRNAs and 1972 lncRNAs were significantly and differentially expressed in ovaries of 1 month and 3 months old Hu sheep (H1 vs H3). These mRNAs and target genes of lncRNAs were primarily enriched in the TGF-β and PI3K-Akt signalling pathways which are closely associated with ovarian follicular development and steroid hormone biosynthesis regulation. We identified MSTRG.162061.1, MSTRG.222844.7, MSTRG.335777.1, MSTRG.334059.16, MSTRG.188947.6 and MSTRG.24344.3 as vital genes in ovary development by regulating CTNNB1, CCNA2, CDK2, CDC20, CDK1 and EGFR expressions. A total of 2903 mRNAs and 636 lncRNAs were differentially expressed in 3 and 8 months old ovaries of Hu sheep (H3 vs H8); and were predominantly enriched in PI3K-Akt, progesterone-mediated oocyte maturation, estrogen metabolism, ovulation from the ovarian follicle and oogenesis pathways. These lncRNAs were also found to regulate FGF7, PRLR, PTK2, AMH and INHBA expressions during follicular development. Our result indicates the identified genes participate in the development of the final stages of follicles and ovary development in Hu sheep.


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