Expression and Functional Role of Peroxisome Proliferator-Activated Receptor-γ in Ovarian Folliculogenesis in the Sheep1

Abstract

Peroxisome proliferator-activated receptor (PPARgamma) is a nuclear receptor that is activated by fatty acids and derivatives and the antidiabetic glitazones, which plays a role in the control of lipid and glucose homeostasis. In the present work, we tested the hypothesis that PPARgamma plays a role in reproductive tissues by studying its expression and function in the hypothalamo-pituitary-ovary axis in the sheep. PPARgamma 1 and PPARgamma 2 proteins and mRNAs were detected in whole ovine pituitary and ovary but not in hypothalamic extracts. In situ hybridization on ovarian section localized PPARgamma mRNA in the granulosa layer of follicles. Interestingly, PPARgamma expression was higher in small antral (1-3 mm diameter) than in preovulatory follicles (>5 mm diameter) (P < 0.001) and was not correlated with healthy status. To assess the biological activity of ovarian PPARgamma, ovine granulosa cells were transfected with a reporter construct driven by PPARgamma-responsive elements. Addition of rosiglitazone, a PPARgamma ligand, stimulated reporter gene expression, showing that endogenous PPARgamma is functional in ovine granulosa cells in vitro. Moreover, rosiglitazone inhibited granulosa cell proliferation (P < 0.05) and increased the secretion of progesterone in vitro (P < 0.05). This stimulation effect was stronger in granulosa cells from small than from large follicles. In contrast, rosiglitazone had no effect on LH, FSH, prolactin and growth hormone secretion by ovine pituitary cells in vitro. Overall, these data suggest that PPARgamma ligands might stimulate follicular differentiation in vivo likely through a direct action on granulosa cells rather than by modulating pituitary hormone secretion.

Potential role for peroxisome proliferator-activated receptor γ in regulating luteal lifespan in the rat

“…There are three isotypes of PPARs: PPARa, PPARb/d, and PPARg. Ovarian tissue from several species, including humans (Lambe & Tugwood 1996), pigs (Schoppe et al 2002), sheep (Froment et al 2003), mice (Cui et al 2002), rats (Braissant et al 1996, Komar et al 2001, and cattle (Sundvold et al 1997, Lohrke et al 1998, expresses PPARg. Although this transcription factor has been detected in the ovaries of several species, to date very little is known regarding the role(s) of PPARg in ovarian function.…”

The effect of nutrition and metabolic status on the development of follicles, oocytes and embryos in ruminants

“…This is because, in addition to the high expression level of PPARγ in the follicle of various species (for review see Froment et al, 2003;Dupont et al, 2008), its synthetic ligands and widely used as drugs treat polycystic ovary syndrome, one of the commonest ovarian dysfunctions causing infertility in women. In ruminants, PPARγ was detected in the ovine and bovine ovary (Sundvold et al, 1997;Lohrke et al, 1998;Froment et al, 2003). In the bovine species, transcripts for RXRα, RXRβ and PPARγ were detected at all stages of early pregnancy beginning from the unfertilized oocyte through to the hatched blastocyst (Mohan et al, 2002) (Table 1).…”

“…In the bovine species, transcripts for RXRα, RXRβ and PPARγ were detected at all stages of early pregnancy beginning from the unfertilized oocyte through to the hatched blastocyst (Mohan et al, 2002) (Table 1). In cyclic ewes, the expression of PPARγ is mainly limited to the granulosa cells of antral follicles and corpora lutea (Froment et al, 2003). In cows, the concentration of PPARγ in the corpus luteum increased after ovulation, and then decreased during regression of the corpus luteum (Lohrke et al, 1998;Viergutz et al, 2000).…”

Un rôle pour PPARγ dans la reproduction ?

“…En effet, chez l'ovin, la sécrétion des hormones hypophysaires LH (luteinizing hormone), FSH (follicle stimulating hormone), PRL (prolactine) et GH (luteinizing hormone) ne semble pas être affectée in vitro en réponse aux TZD [4]. En revanche, plusieurs travaux ont montré qu'au niveau de l'ovaire, PPARγ est fortement exprimé dans les cellules de la granulosa des follicules à antrum ainsi que dans le corps jaune [3,4,7]. Plusieurs études ont également montré que les TZD sont capables de stimuler la sécrétion de progestérone et d'oestradiol par les cellules de la granulosa chez la brebis et la rate.…”

“…En effet, outre son rôle de sensibilisateur à l'action de l'insuline, PPARγ s'est aussi révélé être un régulateur de la masse adipeuse, de la prolifération cellulaire [2], ainsi qu'un modulateur des réactions inflammatoires. On sait maintenant que PPARγ est également exprimé dans les tissus impliqués dans la reproduction: gonades (ovaire, testicule), utérus, glande mammaire, prostate, hypophyse, et au niveau du système nerveux central [3][4][5] (Tableau I, Figure 1). À ce titre, il joue peutêtre un rôle dans le lien qui existe entre le métabolisme énergétique et la reproduction chez les mammifères femelles, comme dans le cas du syndrome des ovaires polykystiques (OPK) qui est majoritairement associé à une résistance à l'action de l'insuline.…”