Comparison of gene expression profiles in granulosa and cumulus cells after ovulation induction with either human chorionic gonadotropin or a gonadotropin releasing hormone agonist trigger

Capsule:
The follicle transcriptomes after human chorionic gonadatropin and gonadotropin-releasing hormone agonist triggering present significant differences. The top biofunctions represented by the differentially expressed genes were steroidogenesis and angiogenesis in cumulus and mural granulosa cells, respectively.

Authors:
Tanni Borgbo, M.Sc., Betina B. Povlsen, M.Sc., Claus Yding Andersen, D.M.Sci., Rehannah Borup, M.Sc., Peter Humaidan, M.D. D.M.Sci., Marie Louise Grøndahl, D.V.M. Ph.D.

Volume 100, Issue 4, Pages 994-1001.e2, October 2013

Abstract:

Objective:
To explore differences in follicle transcriptomes in patients having oocyte maturation with either abolus of hCG or GnRHa.

Design:
Cumulus cells (CC) and mural granulosa cells (MGC) were isolated from preovulatory follicles in patient sundergoing controlled ovarian stimulation, prospectively randomized to GnRHa or hCG triggering.

Setting:
University-based facilities for clinical services and research.

Patient(s):
Twenty women with indication for IVF or intracytoplasmic sperm injection treatment were randomly allocated to hCG or GnRH agonist (GnRHa) trigger.

Intervention(s):
MGC and CC were collected from individual follicles in connection with oocyte retrieval.

Main Outcome Measure(s):
RNA was extracted, labeled, amplified, and hybridized on HumanGene1.0ST GeneChip Affymetrix array. Expression data were robust multichip average normalized and compared using Partek and Ingenuity software. Array data were confirmed with reverse transcription–polymerase chain reaction analysis.

Result(s):
Comparing the transcriptomes between the groups, 391 and 252 genes were differentially expressed (fold change >1.5) in CC and MGC, respectively. The enriched bionetworks showed that CC genes highly represented “lipid metabolism and small molecule biochemistry” (network score, 41), while in MGC, the top network was “cardiovascular development and function and cellular movement” (network score, 50). For both CC and MGC, the regulator analysis suggested LH as the upstream regulator for the difference observed. In CC, the LH receptor was more highly expressed after GnRHa trigger, while in MGC, genes involved in angiogenesis such as angiopoietin 1 and semaphorin 3A were down- and up-regulated, respectively, in GnRHa- as compared with hCG-triggered patients.

Conclusion(s):
The comparisons between somatic cell transcriptomes from GnRHa- and hCG-triggered follicles showed significant functional differences in both CC (steroidogenesis) and MGC (angiogenesis) compartments.

  • Amanda N. Kallen

    Borgbo et al very neatly observed that GnRHa trigger (vs hCG trigger) seems to result in upregulation of genes important in steroidogenesis in the CC compartment (potentially due to increased endogenous gonadotropins). This is an interesting idea and I look forward to additional functional studies to determine the significance of these findings. One comment/critique – the study group included male factor + unexplained + mild endo patients, and the authors did not address in the text whether there is heterogeneity in the expression patterns of these same genes among these different infertility diagnoses. Has this been previously investigated, and / or did the authors further stratify findings by fertility diagnosis and find that these observations still held true?

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