Integrated Transcriptomic Analysis on Chicken Ovary Reveals CYP21A1 Affects Follicle Granulosa Cell Development and Steroid Hormone Synthesis

Overview

Journal Poult Sci

Publisher Elsevier

Specialty Veterinary Medicine

Date 2024 Mar 12

PMID 38471223

Authors

Zhangjing You

Jingwei Yuan

Yuanmei Wang

Yanyan Sun

Aixin Ni

Yunlei Li

Hui Ma

Tenghe Ma

Jilan Chen

Affiliations

Soon will be listed here.

Abstract

Egg production is an economically important trait in poultry breeding and production. Follicular development was regulated by several hormones released and genes expressed in the granulosa cells, impacting the egg production and fecundity of hens. However, the molecular functions of these candidate genes that modulate these processes remain largely unknown. In the present study, bioinformatics analyses were performed to identify the candidate genes related to egg production in the ovarian tissue of White Leghorns with high egg production and Beijing You chicken with low egg production during sexual maturity and peak laying periods. The ovarian granulosa cells were used to assess the function of CYP21A1 by transfecting with CYP21A1-specific small interfering RNAs (siRNAs) and overexpression plasmids. We identified 514 differentially expressed genes (|Log2(fold change) | >1, P <0.05) between the 2 chicken breeds in both laying periods. Among these genes, CYP21A1, which is involved in the steroid hormone biosynthesis pathway was consistently upregulated in White Leghorns. Weighted gene co-expression network analysis (WGCNA) further suggested that CYP21A1 was a hub gene, which could positively respond to treatment with follicle stimulation hormone (FSH), affecting egg production. The interference of CYP21A1 significantly inhibited cell proliferation and promoted cell apoptosis. Overexpression of CYP21A1 promotes cell proliferation and inhibits cell apoptosis. Furthermore, the interference with CYP21A1 significantly downregulated the expression of STAR, CYP11A1, HSD3B1, and FSHR and also decreased the synthesis of progesterone (P4) and estradiol (E2) in granulosa cells. Overexpression of CYP21A1 increased the synthesis of P4 and estradiol E2 and the expression of steroid hormone synthesis-related genes in granulosa cells. Our findings provide new evidence for the biological role of CYP21A1 on granulosa cell proliferation, apoptosis, and steroid hormone synthesis, which lays the theoretical basis for improving egg production.

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References

Naiki Y, Miyado M, Horikawa R, Katsumata N, Onodera M, Pang S . Extra-adrenal induction of Cyp21a1 ameliorates systemic steroid metabolism in a mouse model of congenital adrenal hyperplasia. Endocr J. 2016; 63(10):897-904. DOI: 10.1507/endocrj.EJ16-0112. View

Li J, Luo W, Huang T, Gong Y . Growth differentiation factor 9 promotes follicle-stimulating hormone-induced progesterone production in chicken follicular granulosa cells. Gen Comp Endocrinol. 2019; 276:69-76. DOI: 10.1016/j.ygcen.2019.03.005. View

Tyasi T, Sun X, Shan X, Liswaniso S, Chimbaka I, Qin N . Effects of RAC1 on Proliferation of Hen Ovarian Prehierarchical Follicle Granulosa Cells. Animals (Basel). 2020; 10(9). PMC: 7552126. DOI: 10.3390/ani10091589. View

Zhang C, Zhang X, Xia Y, Cao Y, Wang W, Xu P . Association between polymorphisms of the CYP11A1 gene and polycystic ovary syndrome in Chinese women. Mol Biol Rep. 2012; 39(8):8379-85. DOI: 10.1007/s11033-012-1688-7. View

Tao Z, Song W, Zhu C, Xu W, Liu H, Zhang S . Comparative transcriptomic analysis of high and low egg-producing duck ovaries. Poult Sci. 2017; 96(12):4378-4388. DOI: 10.3382/ps/pex229. View

Chen H, Feng W, Chen K, Qiu X, Xu H, Mao G . Transcriptomic analysis reveals potential mechanisms of toxicity in a combined exposure to dibutyl phthalate and diisobutyl phthalate in zebrafish (Danio rerio) ovary. Aquat Toxicol. 2019; 216:105290. DOI: 10.1016/j.aquatox.2019.105290. View

Wulff C, Wiegand S, Saunders P, Scobie G, Fraser H . Angiogenesis during follicular development in the primate and its inhibition by treatment with truncated Flt-1-Fc (vascular endothelial growth factor Trap(A40)). Endocrinology. 2001; 142(7):3244-54. DOI: 10.1210/endo.142.7.8258. View

Rostamzadeh Mahdabi E, Esmailizadeh A, Ayatollahi Mehrgardi A, Fozi M . A genome-wide scan to identify signatures of selection in two Iranian indigenous chicken ecotypes. Genet Sel Evol. 2021; 53(1):72. PMC: 8428137. DOI: 10.1186/s12711-021-00664-9. View

Xing K, Liu H, Zhang F, Liu Y, Shi Y, Ding X . Identification of key genes affecting porcine fat deposition based on co-expression network analysis of weighted genes. J Anim Sci Biotechnol. 2021; 12(1):100. PMC: 8379819. DOI: 10.1186/s40104-021-00616-9. View

10.

Bu D, Luo H, Huo P, Wang Z, Zhang S, He Z . KOBAS-i: intelligent prioritization and exploratory visualization of biological functions for gene enrichment analysis. Nucleic Acids Res. 2021; 49(W1):W317-W325. PMC: 8265193. DOI: 10.1093/nar/gkab447. View

11.

Shih M, Chiu Y, Hu M, Guo I, Chung B . Regulation of steroid production: analysis of Cyp11a1 promoter. Mol Cell Endocrinol. 2011; 336(1-2):80-4. DOI: 10.1016/j.mce.2010.12.017. View

12.

Vanderhyden B, Telfer E, Eppig J . Mouse oocytes promote proliferation of granulosa cells from preantral and antral follicles in vitro. Biol Reprod. 1992; 46(6):1196-204. DOI: 10.1095/biolreprod46.6.1196. View

13.

Pertea M, Kim D, Pertea G, Leek J, Salzberg S . Transcript-level expression analysis of RNA-seq experiments with HISAT, StringTie and Ballgown. Nat Protoc. 2016; 11(9):1650-67. PMC: 5032908. DOI: 10.1038/nprot.2016.095. View

14.

Venkata Ratna S, Prasada Rao T, Pathipati D, Chaitanya Kumar T, Naik B, Siva Kumar A . Kisspeptin promotes follicular development through its effects on modulation of P450 aromatase expression and steroidogenesis in sheep ovarian follicles. Reprod Domest Anim. 2023; 58(9):1270-1278. DOI: 10.1111/rda.14430. View

15.

Onagbesan O, Bruggeman V, Decuypere E . Intra-ovarian growth factors regulating ovarian function in avian species: a review. Anim Reprod Sci. 2008; 111(2-4):121-40. DOI: 10.1016/j.anireprosci.2008.09.017. View

16.

Zhang T, Chen L, Han K, Zhang X, Zhang G, Dai G . Transcriptome analysis of ovary in relatively greater and lesser egg producing Jinghai Yellow Chicken. Anim Reprod Sci. 2019; 208:106114. DOI: 10.1016/j.anireprosci.2019.106114. View

17.

Su F, Guo X, Wang Y, Wang Y, Cao G, Jiang Y . Genome-Wide Analysis on the Landscape of Transcriptomes and Their Relationship With DNA Methylomes in the Hypothalamus Reveals Genes Related to Sexual Precocity in Jining Gray Goats. Front Endocrinol (Lausanne). 2018; 9:501. PMC: 6125331. DOI: 10.3389/fendo.2018.00501. View

18.

An X, Ma H, Liu Y, Li F, Song Y, Li G . Effects of miR-101-3p on goat granulosa cells and ovarian development via . J Anim Sci Biotechnol. 2020; 11:102. PMC: 7557009. DOI: 10.1186/s40104-020-00506-6. View

19.

Zhong C, Liu Z, Qiao X, Kang L, Sun Y, Jiang Y . Integrated transcriptomic analysis on small yellow follicles reveals that sosondowah ankyrin repeat domain family member A inhibits chicken follicle selection. Anim Biosci. 2020; 34(8):1290-1302. PMC: 8255886. DOI: 10.5713/ajas.20.0404. View

20.

Nelson D . The cytochrome p450 homepage. Hum Genomics. 2009; 4(1):59-65. PMC: 3500189. DOI: 10.1186/1479-7364-4-1-59. View