Molecular determinants of a competent bovine corpus luteum: first- vs final-wave dominant follicles

Abstract

Reproductive management in cattle requires the synchrony of follicle development and oestrus before insemination. However, ovulation of follicles that have not undergone normal physiological maturation can lead to suboptimal luteal function. Here, we investigated the expression of a targeted set of 47 genes in (a) a first-wave vs final-wave dominant follicle (DF; the latter destined to ovulate spontaneously) and (b) 6-day-old corpora lutea (CLs) following either spontaneous ovulation or induced ovulation of a first-wave DF to ascertain their functional significance for competent CL development. Both the mass and progesterone-synthesising capacity of a CL formed following induced ovulation of a first-wave DF were impaired. These impaired CLs had reduced expression of steroidogenic enzymes (e.g. STAR and HSD3B1), luteotrophic receptors (LHCGR) and angiogenic regulators (e.g. VEGFA) and increased expression of BMP2 (linked to luteolysis). Relative to final-wave DFs, characteristic features of first-wave

Transforming growth factor-beta family members are regulated during induced luteolysis in cattle

“…INHBA was upregulated at 2 h, and further increased at 12 h, when INHBB was also upregulated. In agreement with our findings, bovine luteal cells with low progesterone-synthesizing capacity express higher levels of INHBB and INHBA compared to those producing high P4 levels (Gregson et al, 2016). Nonetheless, INHA presented a distinct expression pattern, decreasing at 48 h. Inhibin subunits are also differentially regulated in human follicular fluid throughout the menstrual cycle (Groome et al, 1996).…”

“…Therefore, BMP2 inhibits the effect of hCG in human luteal cells, inhibiting luteinization by suppressing the expression of LH receptor (Shi et al, 2011). Furthermore, it was previously demonstrated that BMP2 abundance was increased in bovine corpora lutea with impaired P4 production (Gregson et al, 2016).…”

Follicle development and selection: past, present and future

“…Also that the increased number of thecal and granulosa cell LH receptors identified during the preovulatory period, is part of the final maturational process that ensures that ovulation will occur in response to the preovulatory LH surge. Subsequent work, including molecular biological studies up to the present day, have confirmed these findings and demonstrated the importance of local components of both the TGF-β and IGF systems that affect the maturation of the ovulatory follicle and functional competency of the subsequent corpus luteum (CL; Gregson et al, 2016).…”

“…Ovine granulosa cells treated with low doses of rhBMP15 alone showed mild increases in FSHstimulated estradiol production while higher doses were markedly inhibitory. Bone morphogenetic protein 15 is, however, known to form heterodimers with GDF9 (Mottershead et al, 2013) and exposure of granulosa cells to both rmGDF9 and rhBMP15 induced a 10-fold increase in estradiol production when compared to the same doses in isolation (A Marsh, J HernandezMedrano, BK Campbell, 2016 unpublished results). Therefore, the physiological importance of BMP15 in ruminant species appears more complex than indicated by the phenotypes observed in the sheep mutation carriers.…”

“…While these less mature follicles can ovulate during the midluteal phase, progesterone production by these induced CL is attenuated (see Webb et al, 1992;Gregson et al, 2016). Gonadotropin-dependent follicles require a constant supply of FSH to continue their development, including the expression of P450 side chain cleavage (P450scc) and P450 aromatase (P450arom) in granulosa cells, together with steroid 17 alpha-hydroxylase (P450c17) in theca cells, which increases the production of estradiol within the granulosa cells of the follicle Garverick et al, 2002).…”