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Variants in the Kisspeptin-GnRH Pathway Modulate the Hormonal Profile and Reproductive Outcomes

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Autor(es):
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Trevisan, Camila Martins [1] ; Naslavsky, Michel Satya [2] ; Monfardini, Frederico [2] ; Wang, Jaqueline [2] ; Zatz, Mayana [2] ; Peluso, Carla [1] ; Pellegrino, Renata [3] ; Mafra, Fernanda [3] ; Hakonarson, Hakon [3] ; Ferreira, Frederico Moraes [4] ; Nakaya, Helder [4] ; Christofolini, Denise Maria [1] ; Montagna, Erik [5] ; Crandall, Keith A. [6] ; Barbosa, Caio Parente [1] ; Bianco, Bianca [1]
Número total de Autores: 16
Afiliação do(s) autor(es):
[1] FMABC, Ctr Univ Saude ABC, Dept Collect Hlth, Discipline Sexual & Reprod Hlth & Populat Genet, Santo Andre 09060870, SP - Brazil
[2] Univ Sao Paulo, Biosci Inst, Human Genome & Stem Cell Res Ctr, Sao Paulo - Brazil
[3] Childrens Hosp Philadelphia, Ctr Appl Genom, Philadelphia, PA 19104 - USA
[4] Univ Sao Paulo, Sch Pharmaceut Sci, Dept Clin & Toxicol Anal, Sao Paulo - Brazil
[5] FMABC, Ctr Univ Saude ABC, Postgrad Program Hlth Sci Res & Innovat, Santo Andre, SP - Brazil
[6] George Washington Univ, Milken Inst Sch Publ Hlth, Computat Biol Inst, Washington, DC - USA
Número total de Afiliações: 6
Tipo de documento: Artigo Científico
Fonte: DNA AND CELL BIOLOGY; v. 39, n. 6 APR 2020.
Citações Web of Science: 0
Resumo

Kisspeptin has been identified as a key regulatory protein in the release of gonadotropin-releasing hormone (GnRH), which subsequently increases gonadotropin secretion during puberty to establish reproductive function and regulate the hypothalamic-pituitary-gonadal axis. The effects of variants in the KISS1, KISS1R, and GNRHR genes and their possible association with assisted reproduction outcomes remain to be elucidated. In this study, we used next-generation sequencing to investigate the associations of the genetic diversity at the candidate loci for KISS1, KISS1R, and GNRHR with the hormonal profiles and reproductive outcomes in 86 women who underwent in vitro fertilization treatments. Variants in the KISS1 and KISS1R genes were associated with luteinizing hormone (rs35431622:T>C), anti-Mullerian hormone (rs71745629delT), follicle-stimulating hormone (rs73507529:C>A), and estradiol (rs73507527:G>A, rs350130:A>G, and rs73507529:C>A) levels, as well as with reproductive outcomes such as the number of oocytes retrieved (s35431622:T>C), metaphasis II oocytes (rs35431622:T>C), and embryos (rs1132506:G>C). Additionally, variants in the GNRHR UTR3 ` (rs1038426:C>A, rs12508464:A>C, rs13150734:C>A, rs17635850:A>G, rs35683646:G>A, rs35610027:C>G, rs35845954:T>C, rs17635749:C>T, and rs7666201:C>T) were associated with low prolactin levels. A conjoint analysis of clinical, hormonal, and genetic variables using a generalized linear model identified two variants of the KISS1 gene (rs71745629delT and rs1132506:G>C) that were significantly associated with hormonal variations and reproductive outcomes. The findings suggest that variants in KISS1, KISS1R, and GNRHR genes can modulate hormone levels and reproductive outcomes. (AU)

Processo FAPESP: 14/06177-2 - Avaliação de mutações/polimorfismos em genes candidatos em mulheres inférteis e sua correlação com resultados de reprodução assistida
Beneficiário:Bianca Alves Vieira Bianco
Linha de fomento: Auxílio à Pesquisa - Regular
Processo FAPESP: 16/25953-9 - Avaliação de mutações e/ou polimorfismos em genes candidatos por sequenciamento de nova geração em mulheres inférteis com e sem endometriose e sua correlação com resultados de estimulação ovariana controlada em tratamentos de reprodução humana assistida
Beneficiário:Bianca Alves Vieira Bianco
Linha de fomento: Auxílio à Pesquisa - Regular