P-582 Novel anti-Mullerian hormone receptor 2 binding peptide (AMHR2BP) modulates murine ovarian follicle cell proliferation and oocyte function in vivo

Abstract Study question We sought to investigate whether the inhibitory effects of the novel peptide AMHR2BP on ovarian cortex gene transcription are translated into decreased protein synthesis. Summary answer AMHR2BP, like recombinant AMH, profoundly inhibited protein transcription of FSH-R, Ki67,...

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Veröffentlicht in:Human reproduction (Oxford) 2022-06, Vol.37 (Supplement_1)
Hauptverfasser: Detti, L, Saed, G
Format: Artikel
Sprache:eng
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Zusammenfassung:Abstract Study question We sought to investigate whether the inhibitory effects of the novel peptide AMHR2BP on ovarian cortex gene transcription are translated into decreased protein synthesis. Summary answer AMHR2BP, like recombinant AMH, profoundly inhibited protein transcription of FSH-R, Ki67, BMP15 and GDF9 in ovarian cortex, confirming its role in inhibition of ovarian function. What is known already We previously showed how anti-Müllerian hormone (AMH) inhibited hormone production, and ovarian cortex follicle development in in vitro, and in vivo, ovarian cortex, and in luteinized granulosa cells. We then developed an AMH receptor 2 binding peptide (AMHR2BP) that could mimic AMH functions and parallel-tested it with AMH. Using histology and real-time RT-PCR we showed that, similarly to AMH, AMHR2BP inhibited granulosa cells replication and function and preserved ovarian follicle number by minimizing the progression of follicular development throughout its administration, in a mouse model. In addition, AMHR2BP decreased follicle hormone production, cell replication and apoptosis, and inhibited oocyte function. Study design, size, duration This was a translational study where 24 18-weeks old C57BL female mice were equally divided and assigned to four treatments: Baseline (euthanized just prior to the experiment), AMHR2BP (AMHR2-BP, 50 µg /day), rAMH (recombinant AMH, 1.8 µg /day), and placebo group (normal saline), administered via intraperitoneal pumps. Mice were euthanized 3 weeks after pump placement and the ovaries were explanted for histology, real-time RT-PCR and ELISA testing. Histology and real-time RT-PCR results were previously reported. Participants/materials, setting, methods We performed ELISA on mouse ovary lysates to quantify protein concentration of FSH receptor (FSH-R), Ki67 (stimulates cell proliferation), and the two oocyte-derived hormones that stimulate mitotic proliferation in granulosa cells, BMP15 and GDF9. Both, BMP15 and GDF9 act in an additive manner and have a critical role in granulosa and theca cell growth, as well as in differentiation and maturation of the oocyte. We used Kruskall-Wallis for comparison of medians (SPSS v25; p < 0.05). Main results and the role of chance Compared with the Baseline and Placebo groups, AMHR2BP and rAMH administration caused a significant decrease in concentration of all the parameters under investigation, indicating inhibition of cellular function. Specifically, a decreased FSH-R indicated
ISSN:0268-1161
1460-2350
DOI:10.1093/humrep/deac105.050