scholarly journals An epigenetic switch repressingTet1in gonadotropes activates the reproductive axis

2017 ◽  
Vol 114 (38) ◽  
pp. 10131-10136 ◽  
Author(s):  
Yahav Yosefzon ◽  
Cfir David ◽  
Anna Tsukerman ◽  
Lilach Pnueli ◽  
Sen Qiao ◽  
...  

The TET enzymes catalyze conversion of 5-methyl cytosine (5mC) to 5-hydroxymethyl cytosine (5hmC) and play important roles during development. TET1 has been particularly well-studied in pluripotent stem cells, butTet1-KO mice are viable, and the most marked defect is abnormal ovarian follicle development, resulting in impaired fertility. We hypothesized that TET1 might play a role in the central control of reproduction by regulating expression of the gonadotropin hormones, which are responsible for follicle development and maturation and ovarian function. We find that all three TET enzymes are expressed in gonadotrope-precursor cells, butTet1mRNA levels decrease markedly with completion of cell differentiation, corresponding with an increase in expression of the luteinizing hormone gene,Lhb. We demonstrate that poorly differentiated gonadotropes express a TET1 isoform lacking the N-terminal CXXC-domain, which repressesLhbgene expression directly and does not catalyze 5hmC at the gene promoter. We show that this isoform is also expressed in other differentiated tissues, and that it is regulated by an alternative promoter whose activity is repressed by the liganded estrogen and androgen receptors, and by the hypothalamic gonadotropin-releasing hormone through activation of PKA. Its expression is also regulated by DNA methylation, including at an upstream enhancer that is protected by TET2, to allowTet1expression. The down-regulation of TET1 relieves its repression of the methylatedLhbgene promoter, which is then hydroxymethylated and activated by TET2 for full reproductive competence.

Author(s):  
L.P. Andrade ◽  
S.M. Rhind ◽  
I.A. Wright ◽  
S.R. McMillen ◽  
T.K. Whyte

Cows in low body condition exhibit a prolonged postpartum anoestrous period and a delayed return to normal follicular function (Prado et al 1990). Previous studies have shown that the effects of body condition on gonadotrophin profiles are inconsistent (Wright et al 1990; Rhind et al 1992) indicating that the effects of body condition on ovarian function cannot be explained by changes in gonadotrophin profiles alone. Since nutritional state influences growth hormone profiles which in turn can affect ovarian function (Gong et al 1991), it was postulated that the effects of body condition on the duration of postpartum anoestrus could be mediated through changes in profiles of this hormone.The aim of the present study was to determine the effect of growth hormone on ovarian follicle development and associated gonadotrophin profiles in post-partum beef cows.


1998 ◽  
Vol 156 (1) ◽  
pp. 213-222 ◽  
Author(s):  
BK Campbell ◽  
H Dobson ◽  
RJ Scaramuzzi

This study examined the effect of LH pulses, of similar amplitude and frequency to those found in the luteal phase, on the pattern of hormone secretion and follicle development in GnRH antagonist-suppressed ewes stimulated with exogenous FSH. This experiment was conducted on ewes with ovarian autotransplants in a continuous study. Follicle development was suppressed in 18 ewes by 3 weeks of GnRH antagonist treatment (50 micrograms/kg per 4 days s.c.), and was then stimulated by infusion of ovine (o)FSH (5 micrograms NIADDK-oFSH-16/h i.v.) for 3 days. In addition to FSH, 10 animals received pulses of LH (2.5 micrograms NIADDK-oLH-26 i.v.) every 4 h for the entire period of the FSH infusion. The follicle population was determined by daily ultrasound. Samples of ovarian and jugular venous blood were collected at 4-h intervals over the period of the FSH infusion and there were three periods of intensive blood sampling (15-min intervals for 2.5 h at 24, 48 and 72 h after the start of the FSH infusion) when the steroidogenic capacity of the follicles in all 18 ewes was tested around an LH challenge (2.5 micrograms i.v.). GnRH antagonist treatment resulted in a 57% decrease in FSH concentrations and prevented ovarian follicle development beyond 3 mm in diameter. Infusion of FSH resulted in a 60% increase in FSH concentrations and stimulated the development of large antral follicles and a coincident increase in ovarian androstenedione, inhibin and oestradiol secretion in both experimental groups. In the absence of 4-hourly LH pulses basal steroid secretion was negligible (< 1 ng/min; P < 0.001). Daily LH challenges, however, revealed no difference in the steroidogenic capacity of the follicle population in either experimental group. Similarly, LH pulses had no effect on the growth rate and number of antral follicles stimulated by FSH infusion, or the pattern of ovarian inhibin secretion. In conclusion, these results show that while FSH alone can stimulate the development of ovulatory sized follicles in ewes made hypogonadal with GnRH antagonist, physiological patterns of LH stimulation have no deleterious effects on FSH-stimulated follicle development and are essential for normal steroidogenesis.


Development ◽  
1976 ◽  
Vol 36 (1) ◽  
pp. 13-18
Author(s):  
J. M. Legay

Ovarian follicle development, which accompanies morphogenesis of the silkworm egg has three distinct phases: spheric, ellipsoidal and flattened-ellipsoid. Transitions between phases are rapid and form-stability (characterized by length/width ratio) is preserved from the beginning of the ellipsoidal phase. The geometric stability of the follicle-oocyte-ovariole system, the polarity of the egg and the determinism in form changes reveal strikingly coordinated spatial and temporal organization.


Sign in / Sign up

Export Citation Format

Share Document