and are required for the maintenance of multipotency in the Müllerian duct mesenchyme.

WNT signaling plays essential roles in the development and function of the female reproductive tract. Although crosstalk with the Hippo pathway is a key regulator of WNT signaling, whether Hippo itself plays a role in female reproductive biology remains largely unknown. Here, we show that conditional deletion of the key Hippo kinases and in mouse Müllerian duct mesenchyme cells caused them to adopt the myofibroblast cell fate, resulting in profound reproductive tract developmental defects and sterility.

and are required for ovarian granulosa cell fate maintenance.

Recent reports suggest that the Hippo signaling pathway influences ovarian follicle development; however, its exact roles remain unknown. Here, we examined the ovarian functions of the Hippo kinases large tumor suppressors (LATS)1 and 2, which serve to inactivate the transcriptional coactivators Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ). Inactivation of in murine granulosa cells either or resulted in a loss of granulosa cell morphology, function, and gene expression.

Expression of the Hippo signalling effectors YAP and TAZ in canine mammary gland hyperplasia and malignant transformation of mammary tumours.

Canine mammary tumours (CMTs) are common neoplasms in dogs that feature many of the clinical, genetic and molecular characteristics of human breast cancer. Despite their high metastatic potential, few adjuvant chemotherapeutic treatment options exist for malignant CMTs, and the development of novel, targeted pharmacological approaches will require a better understanding of their pathogenesis. As recent evidence suggests that dysregulated Hippo signalling is involved in the development and progression of breast cancer, we sought to determine if this pathway could also play a role in CMT.

Pharmacological targeting of valosin containing protein (VCP) induces DNA damage and selectively kills canine lymphoma cells.

Background: Valosin containing protein (VCP) is a critical mediator of protein homeostasis and may represent a valuable therapeutic target for several forms of cancer. Overexpression of VCP occurs in many cancers, and often in a manner correlating with malignancy and poor outcome. Here, we analyzed VCP expression in canine lymphoma and assessed its potential as a therapeutic target for this disease.

β-catenin stabilization in gonadotropes impairs FSH synthesis in male mice in vivo.

Although classically considered a WNT signaling intermediary, β-catenin (CTNNB1) can also mediate GnRH induction of gonadotropin β-subunit (Fshb and Lhb) transcription in the murine gonadotrope-like cell line LβT2. Here, we assessed CTNNB1's role in gonadotropin synthesis in vivo. We used a Cre/lox approach to introduce both gain- and loss-of-function mutations in the murine Ctnnb1 gene in gonadotrope cells.

Effects of bone morphogenetic protein 4 (BMP4) supplementation during culture of the sheep ovarian cortex.

The aim of the present study was to establish the presence of BMP type I and II receptor presence in preantral follicles and to investigate the effect of BMP4 supplementation on preantral follicle activation and development during organotypic culture of prepubertal ovine ovarian cortex pieces. Ovine ovarian fragments were cultured with varying concentrations (0, 25, 50 or 100 ng/ml) of BMP4 in the presence or absence of FSH in the culture media to determine the optimal minimum dose for preantral follicle activation and development. Follicular morphometry, immunohistochemistry for BMPR-IA, BMPR-IB, BMPR-II, proliferating cell nuclear antigen and TUNEL progesterone and 17β-oestradiol production were assessed.

HIF1 activity in granulosa cells is required for FSH-regulated Vegfa expression and follicle survival in mice.

Recent evidence has suggested that vascular endothelial growth factor A (VEGFA) is an important regulator of ovarian follicle development and survival. Both LH and FSH regulate Vegfa expression in granulosa cells and signal via the transcription factor hypoxia inducible factor 1 (HIF1). To further study the mechanism of action of HIF1 in the regulation of Vegfa, we studied Vegfa(delta/delta) mice, which lack a hypoxia response element in the Vegfa promoter.

Regulation of anti-Müllerian hormone production in domestic animals.

In mammals, anti-Müllerian hormone (AMH) expression is detected in the granulosa cells of all growing follicles and is highest in healthy small antral follicles, which contribute most significantly to AMH endocrine levels. AMH is a reliable endocrine marker of this population of gonadotrophin-responsive follicles in ruminants and, over the longer term, plasma AMH concentrations are characteristic of individual animals. In the cow, plasma AMH concentrations follow specific dynamic profiles throughout the prepubertal period, the oestrous cycle and the change from gestation to the post partum period, with the alterations most likely reflecting numerical changes in the population of high AMH-producing follicles.

FZD1 regulates cumulus expansion genes and is required for normal female fertility in mice.

WNT4 is required for normal ovarian follicle development and female fertility in mice, but how its signal is transduced remains unknown. Fzd1 encodes a WNT receptor whose expression is markedly induced in both mural granulosa cells and cumulus cells during the preovulatory period, in a manner similar to Wnt4. To study the physiological roles of FZD1 in ovarian physiology and to determine whether it serves as receptor for WNT4, Fzd1-null mice were created by gene targeting.

Regulation of anti-Müllerian hormone production in the cow: a multiscale study at endocrine, ovarian, follicular, and granulosa cell levels.

Anti-Müllerian hormone (AMH) is an endocrine marker that can help predict superovulatory responses to treatments administered to cows for embryo production. However, the optimal time of the estrous cycle at which a blood test should be performed for a highly reliable prognosis has not yet been established. Moreover, little is known about the regulation of AMH production.

Anti-Müllerian hormone: a predictive marker of embryo production in cattle?

In cattle, the embryo production rate after superovulation varies between individuals and is difficult to predict. Recently, we proposed that anti-Müllerian hormone (AMH) plasma levels measured before treatment can help predict superovulatory responses. To establish whether blood measurement of AMH can help predict the number of embryos produced by a given cow after superovulation, data collected over 4 years from 45 dairy cows submitted to repeated embryo production were analysed in a retrospective study.

Anti-mullerian hormone is an endocrine marker of ovarian gonadotropin-responsive follicles and can help to predict superovulatory responses in the cow.

The major limitation to the development of embryo production in cattle is the strong between-animal variability in ovulatory response to FSH-induced superovulation, mainly due to differences in ovarian activity at the time of treatment. This study aimed to establish whether anti-Müllerian hormone (AMH) was an endocrine marker of follicular populations in the cow, as in human, and a possible predictor of the ovarian response to superovulation. Anti-Müllerian hormone concentrations in plasma varied 10-fold between cows before treatment and were found to be highly correlated with the numbers of 3- to 7-mm antral follicles detected by ovarian ultrasonography before treatment (r=0.