Bone morphogenetic protein 15 supplementation enhances cumulus expansion, nuclear maturation and progesterone production of in vitro‐matured bovine cumulus‐oocyte complexes

Abstract

In vitro embryo production (IVP) efficiency is reduced when compared to in vivo. The basic knowledge of bovine in vitro oocyte maturation (IVM) mechanisms provides support to improve in vitro embryo production yields. The present study assessed the effects of bone morphogenetic protein 15 (BMP15), fibroblast growth factor 16 (FGF16) and their combined action on cumulus cells (CC) expansion, oocyte and CC DNA fragmentation, oocyte nuclear maturation, energetic metabolism and progesterone production in bovine IVM. Cumulus‐oocyte complexes (COC) were matured in control or supplemented media containing BMP15 (100 ng/ml), FGF16 (10 ng/ml) or BMP15 combined with FGF16; and assessed at 0 and 22 hr of IVM. BMP15 alone or its association with FGF16 enhanced cumulus expansion. BMP15 decreased DNA fragmentation in both CC and oocytes, and improved oocyte nuclear maturation rate. In addition, BMP15 increased CC progesterone production, an effect not previously reported. The present study reinforces previous data pointing to a beneficial influence of BMP15 during IVM, while providing novel evidence that the underlying mechanisms involve increased progesterone production.

Gonadotropin elevation is ootoxic to ovulatory oocytes and inhibits oocyte maturation, and activin decoy receptor ActRIIB:Fc therapeutically restores maturation

“…Some improvements to first polar body extrusion rates have been achieved by supplementation of IVM media with antioxidants melatonin, N-acetyl cysteine (NAC), mogroside V, putrecscine, β-cryptoxanthin, peroxiredoxin-4, and resveratrol [ 62 – 68 ]. Oocyte maturation rates in vitro were also improved by myostatin (alias GDF8) and bone morphogenic protein-15 (BMP-15), both of which are members of the TGFβ superfamily [ 69 , 70 ]. Increased rates of PB extrusion were also observed in IVM media supplemented with brain-derived neurotrophic factor, all- trans retinoic acid, leptin, kisspeptin, AY 9944-A-7 (which promotes intrafollicular accumulation of follicular fluid meiosis activating sterol), and growth hormone [ 71 – 76 ].…”

Granulosa Cells Improved Mare Oocyte Cytoplasmic Maturation by Providing Collagens

“…Significantly more enlarged cumulus cells were found in the GC co-culture groups than in the control group, which may be explained by the increased BMP15 expression in oocytes. When BMP15 was added to the IVM medium, it also had a favorable effect on cumulus expansion in bovines ( Caixeta et al, 2013 ; Delgado et al, 2021 ). Moreover, null mutations in BMP15 in oocytes restrict follicular growth, indicating that paracrine factors influence cell viability, cumulus cell expansion, and metabolism during folliculogenesis ( Galloway et al, 2000 ; Su et al, 2008 ).…”

Vitamin D Effects on Folliculogenesis via Ovarian Paracrine Factors

“…GDF9 and BMP15 has an inhibitory effect on progesterone secretion in granulosa cells [21]. In a recent study, it was reported that BMP15 increased progesterone production by cumulus cells [22]. Both GDF9 and BMP15 can act as a potential biomarkers for the estimation of female infertility [23].…”