Low expression of COX‐2, reduced cumulus expansion, and impaired ovulation in SULT1E1‐deficient mice

Gershon, Eran; Hourvitz, Ariel; Reikhav, Sharon; Maman, Ettie; Dekel, Nava

doi:10.1096/fj.06-7688com

Cited by 42 publications

(33 citation statements)

References 50 publications

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“…The regulation of both Sult1e1 and HSD17b7 2 h after hCG would lead to opposite effects on oestrogen bioavailability. Together, these observations suggest that, in the LRH-1 KD model, oestradiol is not the main component that causes the infertility phenotype, and this is further supported by the fact that mouse models of increased oestrogenic activity do not show complete female infertility (Jablonka-Shariff et al 1998;Gershon et al 2007). The different effect on oestradiol in LRH-1-KD mice compared with granulose cell-specific LRH-1-knockout mice (Duggavathi et al 2008) could be explained by the incomplete and temporal nature of KD of LRH-1 in the LRH-1-KD mice.…”

Section: Discussionmentioning

confidence: 76%

Reversible infertility in a liver receptor homologue-1 (LRH-1)-knockdown mouse model

Gerrits

Paradé

Koonen-Reemst

et al. 2014

Reprod. Fertil. Dev.

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Abstract. Liver receptor homologue-1 (LRH-1) is an orphan nuclear receptor that has been implicated in steroid hormone biosynthesis and fertility. Herein we describe a transgenic inducible short hairpin (sh) RNA mouse model that was used to study the effect of transient LRH-1 knockdown in vivo. Induction of expression of the shRNA directed against LRH-1 for 2-6 weeks resulted in 80% knockdown of LRH-1 protein in the ovary and complete infertility. Gonadotropin hyperstimulation could not rescue the observed defects in ovulation and corpus luteum formation in LRH-1-knockdown mice. The infertility phenotype was fully reversible because LRH-1-knockdown females became pregnant and delivered normal size litters and healthy pups after cessation of LRH-1 shRNA expression. Timed ovarian microarray analysis showed that, in line with the observed decrease in plasma progesterone levels, key steroid biosynthesis genes, namely Star, Cyp11a1, Hsd3b and Scarb1, were downregulated in LRH-1-knockdown ovaries. In contrast with what has been described previously, no clear effect was observed on oestrogenic activity in LRH-1-knockdown mice. Only Sult1e1 and, surprisingly, Hsd17b7 expression was modulated with potentially opposite effects on oestradiol bioavailability. In conclusion, the fully reversible infertility phenotype of LRH-1-knockdown mice shows the feasibility of an LRH-1 antagonist as new contraceptive therapy with a mechanism of action that most prominently affects cholesterol availability and progesterone production.

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Section: Discussionmentioning

confidence: 76%

Reversible infertility in a liver receptor homologue-1 (LRH-1)-knockdown mouse model

Gerrits

Paradé

Koonen-Reemst

et al. 2014

Reprod. Fertil. Dev.

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“…It was reported that dominant follicles have greater concentrations of E2 in their follicular fluid in comparison to the subordinate follicles [37,38]. And also, a critical decrease in E2, after the LH surge, is necessary to enable normal ovulation in rodent [39]. Gershon et al demonstrated that estrogen inactivation might allow the LH-induced expression of cyclooxygenase-2 (COX-2) and subsequent C-OE, allowing normal ovulation.…”

Section: Discussionmentioning

confidence: 99%

Felis catus ovary as a model to study follicle biology in vitro

Rojo

Linari

Musse

et al. 2015

J Assist Reprod Genet

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Purpose The current study was designed to evaluate the response of individual intact antral follicles from adult female domestic cats to a luteinizing hormone (LH) stimulus in vitro by assessing cumulus-oocyte expansion (C-OE) and steroid production. Methods C-OE and steroid levels (estradiol [E2] and progesterone [P4]) obtained from individual antral feline follicles (n=366 follicles; n=56 cats) were analyzed after 12 or 24 h of culture in the presence or absence of LH (low [3.4 ng/ml] or high [100 ng/ml]). Results At the end of the culture, the highest percentage of expanded cumulus-oocyte complexes (COCs) was observed in the LH groups at 12 or 24 h in comparison to their controls (p<0.001). There was a significant increase in expanded COCs when comparing LH concentrations (high vs. low) at 12 or 24 h. Higher levels of both E2 and P4 were observed in the media from antral follicles after 12 and 24 h of culture in the presence of LH (both concentration, p<0.05). There was no association between hormone levels and follicle diameter; high variability was observed in the steroid levels produced by antral follicles within all treatment groups.Conclusions These data indicate, for the first time, that feline antral follicles (0.5-2 mm) from different stages of the natural estrous cycle can be cultured and will respond to an LH stimulus, based on an increase in steroid levels as well as C-OE after 12 or 24 h in culture.

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“…ЦОГ2 запускає сигналізацію простаглан-динів (ПГ) у яєчнику, які синтезуються з арахідонової кислоти [29]. ПГ є загальними медіаторами запальних реакцій, включаючи й овуляцію.…”

Section: оглядиunclassified

Cumulus Cell Genes as Potential Biomarkers of Oocyte and Embryo Developmental Competence

Shepel¹,

Voznesenskaya²,

Blashkiv³

et al. 2015

Fiziol Zh

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Low expression of COX‐2, reduced cumulus expansion, and impaired ovulation in SULT1E1‐deficient mice

Cited by 42 publications

References 50 publications

Reversible infertility in a liver receptor homologue-1 (LRH-1)-knockdown mouse model

Reversible infertility in a liver receptor homologue-1 (LRH-1)-knockdown mouse model

Felis catus ovary as a model to study follicle biology in vitro

Cumulus Cell Genes as Potential Biomarkers of Oocyte and Embryo Developmental Competence

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