Effects of Follicle Size and Oocyte Maturation Conditions on Maternal Messenger RNA Regulation and Gene Expression in Rhesus Monkey Oocytes and Embryos1

Abstract

The relationship between alterations in gene expression and differences in developmental potential in primate oocytes and embryos was examined. Oocytes from 3 sources were used for these studies: 1) in vivo-matured oocytes from monkeys stimulated with FSH and hCG, 2) in vitro-matured oocytes from large follicles of monkeys primed with FSH, and 3) in vitro-matured oocytes from small follicles from nonstimulated (NS) monkeys. Following in vitro fertilization, embryos from these oocytes displayed high, moderate, and low developmental competence, respectively. Oocytes from NS females displayed aberrant accumulation of a number of maternal mRNAs, followed by precocious loss of many maternal mRNAs by the 2-cell stage. Embryos from NS oocytes displayed alterations in expression of key transcription factors after the 8-cell stage. Oocytes and embryos from FSH-stimulated females also displayed alterations in gene expression relative to hCG-stimulated females, but these alterations were much less severe than those observed for NS oocytes and embryos. Our data are consistent with the hypothesis that continued development and maturation of the oocyte within the ovarian follicle in vivo facilitates the production of oocytes of the highest developmental potential, and that in vitro conditions may not support this process as effectively due to differences in the extracellular milieu. These observations are relevant to understanding the role of the in vivo environment on oocyte maturation, and the potential effects of in vitro maturation on human assisted reproduction methods.

The antral follicle: a microenvironment for oocyte differentiation

“…The results also imply functional alterations in steroid biosynthesis and metabolism, ion transport, cellular homeostasis, cell growth, stress response, and RNA binding and translation. Similar findings regarding upregulation of transcripts in IVM or incompetent oocytes have been reported in rhesus monkeys and humans (Zheng et al, 2005;Jones et al, 2008). It seems likely that both the oocyte and its supportive somatic cells are sensitive to the maturation environment and that a disruption of that environment can, by upsetting oocyte-somatic cell interactions, affect the transcriptional activity of the oocyte.…”

Molecular control of mitochondrial function in developing rhesus monkey oocytes and preimplantation-stage embryos

“…Oocytes matured in vitro from NS rhesus females display poor developmental competence (Zheng et al 2005) compared with 'in vivo-matured' oocytes. In vitro maturation of oocytes from FSH-primed females yields intermediate-quality oocytes (Schramm and Bavister 1994).…”

“…Previous studies have revealed significant differences between mouse and human or non-human primate embryonic patterns of gene expression (Vassena et al 2005;Zheng et al 2005;Latham 2007, 2008), highlighting the value of a non-human primate model for detailed studies of developmental transitions and developmental mechanisms that may drive human embryogenesis. In addition, critical comparisons to understand the molecular basis of defective embryogenesis require the expenditure of high-quality oocytes and embryos for molecular analysis, which is precluded for the human by legal and ethical considerations.…”

“…Previous studies revealed that many maternal mRNAs become precociously degraded during development to the two-cell stage in embryos derived by in vitro maturation and fertilisation of oocytes isolated from NS females (Zheng et al 2005;Latham 2007, 2008). Given the importance of mitochondrial biogenesis and the trend for significant contribution of maternally encoded mRNAs to developmental patterns of expression outlined above, the expression of these mRNAs was compared between embryos that developed from NS oocytes and oocytes from FSH-or FSH+hCG-stimulated females (low, intermediate, and high developmental potential, respectively).…”

Effects of in vitro maturation of monkey oocytes on their developmental capacity

“…However, with the PREGER project (Zheng et al, 2004a(Zheng et al, , b, 2005a, more than 100 genes have been examined for their expression patterns in oocytes and preimplantation embryos have been assessed from three different sources: oocytes from non-stimulated small follicles, oocytes from FSH-stimulated large follicles, and oocytes from both FSH-and LH-stimulated follicles and matured in vivo. The first source of oocytes represents the population with least developmental competence, the third one represents oocytes with greatest developmental potential and the second represents those with intermediate potential.…”