Akt and Erk signal transduction pathways are early markers of differentiation in dominant and subordinate ovarian follicles in cattle

The LH surge induces a multitude of events that are essential for ovulation and corpus luteum formation. The transcriptional responses to the LH surge of preovulatory granulosa cells (GCs) are complex and still poorly understood. In this study, a genome-wide bovine oligo array was used to determine how the gene expression profile of GCs is modulated by the LH surge. GCs from three different stages were used to assess the short-and long-term effects of this hormone on follicle differentiation: 1) 2 h before induction of the LH surge, 2) 6 h and 3) 22 h after the LH surge. The results obtained were a list of differentially expressed transcripts for each GC group. To provide a comprehensive understanding of the processes at play, biological annotations were used to reveal the different functions of transcripts, confirming that the LH surge acts in a temporal manner. The pre-LH group is involved in typical tasks such as cell division, development, and proliferation, while the early response to the LH surge included features such as response to stimulus, vascularization, and lipid synthesis, which are indicative of cells preparing for ovulation. The late response of GCs revealed terms associated with protein localization and intracellular transport, corresponding to the future secretion task that will be required for the transformation of GCs into corpus luteum. Overall, results described in this study provide new insights into the different transcriptional steps that GCs go through during ovulation and before luteinization.

Section: Discussionsupporting

confidence: 72%

Transcriptional effect of the LH surge in bovine granulosa cells during the peri-ovulation period

Gilbert¹,

Robert²,

Dieleman³

et al. 2011

“…Ryan et al (2007) recently reported that both pathways, which are important for dominant follicle selection, show several differences in their expression profile in cattle follicles. However, few reports have investigated differences between the AKT and ERK pathways in expression, effects, and regulation in granulosa cells.…”

Section: Discussionmentioning

confidence: 99%

IGF1-induced AKT phosphorylation and cell proliferation are suppressed with the increase in PTEN during luteinization in human granulosa cells

Goto

Iwase

Harata³

et al. 2009

Granulosa cells proliferate and then undergo differentiation; an inverse relationship between these processes is observed during terminal follicular growth. During terminal follicular growth and initial luteinization, there is a necessary transition of granulosa cells to a less proliferative and highly steroidogenic form in response to LH. Although the expression of several molecules has been reported to be up-regulated by LH, proliferation/differentiation transition is not fully understood. Here, we show that the expression of a tumor suppressor, phosphatase and tensin homologue deleted on chromosome 10 (PTEN) was induced with human chorionic gonadotropin (hCG) treatment in human luteinized granulosa cells. Pretreatment with hCG attenuated insulin-like growth factor (IGF)-1-induced phosphorylation of AKT and cell proliferation, not phosphorylation of ERK1/2. Moreover, suppression of hCG-induced PTEN expression with siRNA increased AKT phosphorylation and cell proliferation in response to IGF1. We also demonstrate that a PI3K inhibitor, LY294002, not a MEK inhibitor, PD98059, inhibited IGF1-induced cell proliferation. In conclusion, PTEN induced to express by hCG in luteinized granulosa cells that inactivates AKT, not ERK, and attenuates IGF1-induced cell proliferation. PTEN expression may be a trigger for proliferation/differentiation transition in human granulosa cells.

“…In comparison with subordinate follicles, dominant follicles have elevated follicular fluid E 2 concentrations (Fortune et al 2001, Ouellette et al 2005, Ryan et al 2007, Sisco & Pfeffer 2007) and synthetic capacity (Fortune et al 2001, Rhodes et al 2001, and increased free insulin-like growth factor 1 and decreased IGFBP4 and -5 (Beg & Ginther 2006). The dominant follicle in a first wave of the cycle is also slightly larger than one in a second wave (Manikkam et al 2001), and these have higher follicular fluid E 2 concentrations (Wolfenson et al 1999).…”

Section: Dominant and Subordinate Folliclesmentioning

confidence: 99%

Morphological classification of bovine ovarian follicles

Rodgers¹,

Irving-Rodgers²

2010

129

Follicle classification is an important aid to the understanding of follicular development and atresia. Some bovine primordial follicles have the classical primordial shape, but ellipsoidal shaped follicles with some cuboidal granulosa cells at the poles are far more common. Preantral follicles have one of two basal lamina phenotypes, either a single aligned layer or one with additional layers. In antral follicles !5 mm diameter, half of the healthy follicles have columnar shaped basal granulosa cells and additional layers of basal lamina, which appear as loops in cross section ('loopy'). The remainder have aligned single-layered follicular basal laminas with rounded basal cells, and contain better quality oocytes than the loopy/columnar follicles. In sizes O5 mm, only aligned/rounded phenotypes are present. Dominant and subordinate follicles can be identified by ultrasound and/or histological examination of pairs of ovaries. Atretic follicles !5 mm are either basal atretic or antral atretic, named on the basis of the location in the membrana granulosa where cells die first. Basal atretic follicles have considerable biological differences to antral atretic follicles. In follicles O5 mm, only antral atresia is observed. The concentrations of follicular fluid steroid hormones can be used to classify atresia and distinguish some of the different types of atresia; however, this method is unlikely to identify follicles early in atresia, and hence misclassify them as healthy. Other biochemical and histological methods can be used, but since cell death is a part of normal homoeostatis, deciding when a follicle has entered atresia remains somewhat subjective.