FGF18 impairs blastocyst viability, DNA double-strand breaks and maternal recognition of pregnancy genes

• Published in: Theriogenology Vol. 225; pp. 81 - 88
• Main Authors: Goetten, André Lucio Fontana, Barreta, Marcos Henrique, Pinto da Silva, Yago, Bertolin, Kalyne, Koch, Júlia, Rocha, Cecilia Constantino, Dias Gonçalves, Paulo Bayard, Price, Christopher Alan, Antoniazzi, Alfredo Quites, Portela, Valerio Marques
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.09.2024
• Subjects: Animals; Blastocyst - drug effects; Blastocyst - physiology; Cattle; DNA Breaks, Double-Stranded; DNA repair; Embryo Culture Techniques - veterinary; Embryo development; Embryonic Development - drug effects; Female; FGF; Fibroblast Growth Factors - genetics; Fibroblast Growth Factors - metabolism; Gene Expression Regulation, Developmental - drug effects; IFNT2; In Vitro Oocyte Maturation Techniques - veterinary; Oocyte maturation; Pregnancy; IFNT2; FGF; DNA repair; Embryo development; Oocyte maturation
• ISSN: 0093-691X; 1879-3231
• DOI: 10.1016/j.theriogenology.2024.05.020

Embryonic mortality in cattle is high, reaching 10–40 % in vivo and 60–70 % in vitro. Death of embryos involves reduced expression of genes related to embryonic viability, inhibition of DNA repair and increased DNA damage. In follicular granulosa cells, FGF18 from the theca layer increases apoptosis and DNA damage, so we hypothesized that FGF18 may also affect the oocyte and contribute to early embryonic death. The aims of this study were to identify the effects of FGF18 on cumulus expansion, oocyte maturation and embryo development from cleavage to blastocyst stage using a conventional bovine in vitro embryo production system using ovaries of abattoir origin. Addition of FGF18 during in-vitro maturation did not affect FSH-induced cumulus expansion or rates of nuclear maturation. When FGF18 was present in the culture system, rates of cleavage were not affected however, blastocyst and expanded blastocyst development was substantially inhibited (P < 0.05), indicating a delay of blastulation. The number of phosphorylated histone H2AFX foci per nucleus, a marker of DNA damage, was higher in cleavage-stage embryos cultured with FGF18 than in those from control group (P < 0.05). Furthermore, FGF18 decreased accumulation of PTGS2 and IFNT2 mRNA in blastocysts. In conclusion, these novel findings suggest that FGF18 plays a role in the regulation of embryonic death during the early stages of development by impairing DNA double-strand break repair and expression of genes associated with embryo viability and maternal recognition of pregnancy during the progression from oocyte to expanded blastocysts. •FGF18 had no effect on cumulus expansion, oocyte nuclear maturation, or embryo development from cleavage stage.•FGF18 added during IVM increased DNA double-strand breaks in cleavage-stage embryos.•FGF18 impaired development to the blastocyst and expanded blastocyst stages.•FGF18 added during embryo culture reduced abundance of PTGS2 mRNA, an embryo viability marker, and mRNA encoding IFNT2, a protein responsible for maternal recognition of pregnancy.