Effects of metoclopramide on the mouse anterior pituitary during the estrous cycle

Gomes, Regina Célia Teixeira; Verna, Carina; Simões, Ricardo Santos; Wolff, R; Baracat, Edmund Chada; Soares-Jr, José Maria

doi:10.1590/s1807-59322011000600031

Cited by 7 publications

(1 citation statement)

References 29 publications

(35 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Med12 fl/fl Amhr2-Cre mice spent more time in the metestrus stage than controls (23.20 ± 1.86 vs 13.60 ± 1.63, n = 5, P < 0.01) (Figure 2D). Metestrus stage correlates with decline in estradiol and progesterone levels, and both vaginal cornification and estrous cycle are dependent on circulating estradiol levels [26,27]. The abnormal estrous cycles indicate problems with steroidogenesis and impaired ovarian function in Med12 fl/fl Amhr2-Cre mice.…”

Section: Med12 Disrupts Estrous Cyclicitymentioning

confidence: 99%

Med12 regulates ovarian steroidogenesis, uterine development and maternal effects in the mammalian egg†

Mittal

Castro

Rajkovic

et al. 2017

Biology of Reproduction

View full text Add to dashboard Cite

The transcriptional factor MED12 is part of the essential mediator transcriptional complex that acts as a transcriptional coactivator in all eukaryotes. Missense gain-of-function mutations in human MED12 are associated with uterine leiomyomas, yet the role of MED12 deficiency in tumorigenesis and reproductive biology has not been fully explored. We generated a Med12 reproductive conditional knockout mouse model to evaluate its role in uterine mesenchyme, granulosa cells, and oocytes. Mice heterozygous for Med12 deficiency in granulosa cells and uterus (Med12fl/+ Amhr2-Cre) were subfertile, while mice homozygous for Med12 deficiency in granulosa cells and uterus (Med12fl/fl Amhr2-Cre) were infertile. Morphological and histological analysis of the Med12fl/fl Amhr2-Cre reproductive tract revealed atrophic uteri and hyperchromatic granulosa cells with disrupted expression of Lhcgr, Esr1, and Esr2. Med12fl/fl Amhr2-Cre mice estrous cycle was disrupted, and serum analysis showed blunted rise in estradiol in response to pregnant mare serum gonadotropin. Uterine atrophy was partially rescued by exogenous steroid supplementation with dysregulation of Notch1 and Smo expression in steroid supplemented Med12fl/fl Amhr2-Cre uteri, indicating intrinsic uterine defects. Oocyte-specific ablation of Med12 caused infertility without disrupting normal folliculogenesis and ovulation, consistent with maternal effects of Med12 in early embryo development. These results show the critical importance of Med12 in reproductive tract development and that Med12 loss of function does not cause tumorigenesis in reproductive tissues.

show abstract

Section: Med12 Disrupts Estrous Cyclicitymentioning

confidence: 99%