Inhibin A is a follicle stimulating hormone-responsive marker of granulosa cell differentiation, which has both autocrine and paracrine actions in sheep

Campbell, B. K.; Baird, D. T.

doi:10.1677/joe.0.1690333

Cited by 77 publications

(39 citation statements)

References 49 publications

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“…Once again, this may have arisen, at least in part, from the increased response of granulosa cells to FSH. In vivo and in vitro studies have previously demonstrated that estradiol production by granulosa cells is FSH responsive in this species [37,38]. Estradiol is known to exert some of its actions in a paracrine manner via one of two receptors (i.e., ESR1 and ESR2), and both isoforms are expressed in sheep granulosa cells during the late preantral and antral stages of follicle development [39], coincident with the period of exposure to dietary treatments in the current study.…”

Section: Nature and Timing Of Dietary Effectssupporting

confidence: 58%

B-Vitamin and Homocysteine Status Determines Ovarian Response to Gonadotropin Treatment in Sheep1

Raji

Singh

et al. 2009

Biology of Reproduction

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Maternal B-vitamin status and homocysteinemia can affect fertility and pregnancy establishment, although the direct effects on ovarian follicle and oocyte development are not known. We report on the effects of restricting the supply of vitamin B(12) and methionine from the diet of mature female sheep on ovarian folliculogenesis following follicle-stimulating hormone (FSH) stimulation. The study was split into three batches and involved 76 animals. Surprisingly, the number of growing, estrogen-active antral follicles following FSH treatment was enhanced (P = 0.005) following this dietary intervention. This increase occurred even in the presence of modest live-weight loss (batch 1 only) and depressed plasma insulin concentrations, suggesting a breakdown in the regulation of follicular responsiveness to FSH. This dietary intervention also increased plasma homocysteine concentrations. Physiological concentrations of homocysteine increased granulosa cell proliferation (P < 0.001), estradiol production (P = 0.05), and FSHR transcript expression (P = 0.017) during culture. Transcript levels for growth differentiation factor 9 and bone morphogenetic protein 15 in oocytes from treated ewes were increased (P < 0.05) in the first two batches. Furthermore, regression of BMP receptor 2 (BMPR2) transcript expression and diet on follicle number revealed a significant interaction (P = 0.01); BMPR2 transcript expression was associated with follicle number only in vitamin B(12)/methionine-restricted animals. Because FSHR transcript expression also was positively (P = 0.007) related to follicle number, the effects of diet may have arisen through enhanced FSH and BMP signaling. Although this remains to be confirmed, the data support an intraovarian impact of vitamin B(12)/methionine-deficient diets.

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Section: Nature and Timing Of Dietary Effectssupporting

confidence: 58%

B-Vitamin and Homocysteine Status Determines Ovarian Response to Gonadotropin Treatment in Sheep1

Raji

Singh

et al. 2009

Biology of Reproduction

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“…Functionality of preovulatory follicles can be assessed both by direct (assessment of their growth dynamics and/or hormonal secretion) and indirect approaches (assessment of subordinate follicles for evidencing dominance effects driven by hormonal secretion of the large follicles). In sheep, E 2 and inhibin-A are considered as good markers of follicular quality (Campbell et al 1995, Campbell & Baird 2001, Gonzalez-Bulnes et al 2004c and, in the current study, both hormones were reduced in older ewes. In women, both E 2 and inhibin-A decrease during the ovarian aging process, although there is an earlier decrease in inhibin-B (Broekmans et al 2009), a hormone which is not produced by the sheep ovary (McNeilly et al 2002).…”

Section: Discussionsupporting

confidence: 57%

Effect of aging on follicular function may be relieved by exogenous gonadotropin treatment in a sheep model

Berlinguer

González-Bulnes²,

Spezzigu³

et al. 2012

Reproduction

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The current study investigated hormonal and ovarian changes during physiological reproductive aging in Sarda ewes. In a first experiment, follicular and corpus luteum dynamics were compared during an induced oestrus cycle in aged (12-14 years) and young adult ewes (4-5 years). Oestrus cycle characteristics did not differ between the two experimental groups. However, follicular function during the follicular phase showed significant alterations in aged ewes, as determined by a lack of dominance effect and by lower mean values of circulating oestradiol (E 2 ) and inhibin levels, compared with young adult ewes. In a second experiment, differences in follicle growth, hormonal milieu and oocyte quality in response to exogenous FSH administration were assessed in aged and adult ewes. No differences were recorded in ovarian response to FSH treatment between young adult and aged ewes, as evaluated by ultrasonographic data and circulating concentrations of LH, E 2 and inhibin-A. Although the total number of recovered oocytes was similar in the two age groups, the number of good quality oocytes selected for IVM was significantly lower in aged ewes compared with adult ones. Thereafter, no differences were recorded in cleavage rates, total blastocyst output, embryo developmental kinetic and quality between aged and adult groups. In conclusion, this study demonstrated that reproductive aging in sheep is associated with impaired follicle functionality and an increase in the proportion of oocytes showing morphological abnormalities. However interestingly, oocyte developmental competence in vitro and embryo cryotolerance were not affected by the aging process, when only good quality oocytes were chosen.

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“…Thus in the mouse we have no evidence for production of inhibins outwith the granulosa compartment. In a recent study in the sheep using in situ hybridization, expression of all inhibin subunits was also confined to the granulosa cells (Campbell & Baird 2001).…”

Section: Discussionmentioning

confidence: 96%

Influence of mutations affecting gonadotropin production or responsiveness on expression of inhibin subunit mRNA and protein in the mouse ovary

Hirst

Abel²,

Wilkins³

et al. 2004

Reproduction

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Measurement of inhibins A and B in the serum of normal cyclic rodents has implicated FSH in the regulation of these peptides within the ovary. To extend these observations we have used a panel of mutant mice carrying mutations which affect either the production of, or the ability to respond to, FSH and LH. As a consequence, the females are infertile and show different degrees of follicular development. The aim of this study was to measure inhibin gene transcription in the ovaries of these mutant females together with inhibin protein levels in ovaries and serum and to relate these to follicular development within the ovary. Comparison was made with a pool of normal/heterozygous females. In hpg females where lack of GnRH production results in the absence of gonadotropin synthesis, in FSHb knockout (FSHbKO) females where disruption of the gene encoding FSHb results in the absence of FSH production, and in FSH receptor knockout (FSHRKO) females which are unable to respond to circulating FSH, follicular development remains at the pre-antral stage in these three mutants. Only in the hpg females were common inhibin a subunit mRNA levels significantly lower than normal. In these three mutants, however, mRNA levels for both the bA and bB subunits were extremely low compared with normal mice. At the protein level, neither inhibin A nor B was detected in the serum of these three mutants; however inhibin B, albeit at very low levels, was detectable within the ovaries. These observations confirm a major role for FSH in the control of transcription of the bA and bB genes but suggest that the constitutive transcription of the alpha subunit is less dependent on FSH. In contrast, in LH receptor knockout (LuRKO) female mice inhibin bA subunit mRNA levels were similar to those measured in normal/heterozygous females but levels of inhibin a and bB subunit mRNAs were significantly higher than in the normal group. This was reflected in significantly higher inhibin B protein levels in ovaries and serum. An inability to respond to LH combined with high circulating levels of FSH leads to a high proportion of antral follicles in LuRKO females, with granulosa cells constituting the major cell type within the ovary. The high percentage of antral granulosa cells is likely to account for the significantly higher levels of inhibin B production in these ovaries.

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Inhibin A is a follicle stimulating hormone-responsive marker of granulosa cell differentiation, which has both autocrine and paracrine actions in sheep

Cited by 77 publications

References 49 publications

B-Vitamin and Homocysteine Status Determines Ovarian Response to Gonadotropin Treatment in Sheep1

B-Vitamin and Homocysteine Status Determines Ovarian Response to Gonadotropin Treatment in Sheep1

Effect of aging on follicular function may be relieved by exogenous gonadotropin treatment in a sheep model

Influence of mutations affecting gonadotropin production or responsiveness on expression of inhibin subunit mRNA and protein in the mouse ovary

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