Gustavo Zamberlam's research while affiliated with Université de Montréal and other places

Publications (30)

Article
Full-text available
The cortex of the adrenal gland is organized into concentric zones that produce distinct steroid hormones essential for body homeostasis in mammals. Mechanisms leading to the development, zonation and maintenance of the adrenal cortex are complex and have been studied since the 1800s. However, the advent of genetic manipulation and transgenic mouse...
Article
Full-text available
The molecular mechanisms that drive the granulosa cells’ (GC) differentiation into a more estrogenic phenotype during follicular divergence and establishment of follicle dominance have not been completely elucidated. The main Hippo signaling effector, YAP, has, however, emerged as a potential key player to explain such complex processes. Studies us...
Article
Full-text available
Hippo signaling plays an essential role in the development of numerous tissues. Although it was previously shown that the transcriptional effectors of Hippo signaling Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) can fine-tune the regulation of sex differentiation genes in the testes, the role of Hippo si...
Article
Context: The establishment of pregnancy in cows requires uterine activity regulation of the main Hippo signalling effector yes-associated protein 1 (YAP). It remains unknown (1) how YAP activity at the corpus luteum (CL) correlates with early pregnancy-related events in ruminants; and (2) if YAP activity in the uterus and CL can be affected by met...
Article
Full-text available
Recent conditional knockout of core components of the Hippo signaling pathway in the adrenal gland of mice has demonstrated that this pathway must be tightly regulated to ensure proper development and maintenance of the adrenal cortex. We report herein that the most upstream kinases of the pathway, the mammalian STE20-like protein kinases 1 and 2 (...
Article
Full-text available
Purpose: To determine if the inhibition of the interaction between the Hippo effector YAP or its transcriptional co-activator TAZ with the TEAD family of transcription factors is critical for the cumulus expansion-related events induced by the EGF network in cumulus-oocyte complexes (COCs). Methods: We performed a series of experiments using imm...
Article
The Hippo transcriptional coactivators YAP and TAZ exert critical roles in morphogenesis, organ size determination and tumorigenesis in many tissues. Although Hippo kinase cascade activity was recently reported in the anterior pituitary gland in mice, the role of the Hippo effectors in regulating gonadotropin production remains unknown. The objecti...
Article
Failure to ovulate is a major cause of infertility. The critical pathway that induces ovulation involves the EGF and MAPK phosphorylation, but studies in rodents have suggested that the Hippo activator, YAP, is also involved. It is unknown whether YAP-dependent transcriptional activity is important for the LH- or EGF-induced ovulatory cascade in mo...
Article
WNT signaling regulates a variety of ovarian processes including follicle development, granulosa cell (GC) proliferation and differentiation, steroidogenesis and ovulation. The secreted frizzled-related proteins (SFRPs) comprise a family of WNT signaling antagonists. Sfrp4 expression was previously reported to be induced in ovarian GCs and cumulus...
Article
The generation of free-radicals such as nitric oxide has been implicated in the regulation of ovarian function, including ovulation. Tissues that generate nitric oxide typically generate another free-radical gas, hydrogen sulfide (H⁠2S), although little is known about the role of H⁠2S in ovarian function. The hypothesis of this study was that H⁠2S...
Article
Full-text available
Both Wnt4 and Wnt5a have well-established roles in the embryonic development of the female reproductive tract, as well as in implantation, decidualization and ovarian function in adult mice. Although these roles appear to overlap, whether Wnt5a and Wnt4 are functionally redundant in these tissues has not been determined. Here, we addressed this by...
Article
Full-text available
Whereas the roles of the canonical wingless-type MMTV (mouse mammary tumor virus) integration site family (WNT) signaling pathway in the regulation of ovarian follicle growth and steroidogenesis are now established, noncanonical WNT signaling in the ovary has been largely overlooked. Noncanonical WNTs, including WNT5a and WNT11, are expressed in gr...
Article
Alopecia X in dogs is a noninflammatory alopecia that may be caused by a hormonal dysfunction. It may be similar to androgenic alopecia in men that is caused by the effect of dihydrotestosterone (DHT). The 5α-reductase isoenzymes, 5αR1 and 5αR2, and a recently described 5αR3, are responsible for the conversion of testosterone into DHT. However, whi...
Article
Full-text available
Although the various members of the fibroblast growth factor (FGF) family are generally mitotic, one member, FGF18, has been shown increase the rate of apoptotsis of ovarian granulosa cells. In the present study, we determined first whether granulosa cells express FGF18 and we then explored the mechanism through which FGF18 increases apoptosis in v...
Article
In rabbits and rodents, nitric oxide (NO) is generally considered to be critical for ovulation. In monovulatory species, however, the importance of NO has not been determined, nor is it clear where in the preovulatory cascade NO may act. The objectives of the present study were (1) to determine if nitric oxide synthase (NOS) enzymes are regulated b...
Article
The ovarian promoter of the primate and rodent genes encoding cytochrome P450 aromatase (CYP19A1) are robustly responsive to forskolin in luteinized cell models, whereas the ruminant ovarian promoter is minimally active. We explored this discrepancy by investigating the activity of the bovine ovarian promoter in two bovine granulosa cell models, lu...
Conference Paper
Fibroblast growth factors (FGFs) are involved in the paracrine modulation of ovarian function, and typically exert mitogenic effects by inhibiting apoptosis and increasing cell proliferation. However, in a previous study with bovine granulosa cells we observed one FGF had the opposite effect; addition of FGF18 increased caspase-3 activation and inc...
Article
Fertility in dairy and beef cows is negatively affected by stressors such as lamness and high milk yield, and one site of action of these stressors is the process of ovulation. Rupture of the follicle is initiated by the preovulatory surge of LH, which stimulates granulosa cell release of the EGF-like ligands epiregulin (EREG) and amphiregulin (ARE...
Article
Low fertility in the dairy industry is a multifaceted problem, but poor follicle growth and failure to ovulate are major contributors. The health of the granulosa cell layer of the follicle is key to follicle growth, and an essential mitogenic, anti-apoptotic product of granulosa cells is estradiol. The rate-limiting enzyme for estradiol synthesis...
Article
Angiotensin II (AGT-2) induces follicular prostaglandin release in a number of species and ovulation in rabbits. Conversely, AGT-2 antagonists block ovulation in cattle. To determine the mechanism of action of AGT-2, we used a bovine granulosa cell model in which luteinizing hormone (LH) increased the expression of genes essential for ovulation in...
Article
Nitric oxide (NO) is a potential regulator of ovarian follicle growth, and ovarian granulosa cells reportedly generate NO in response to gonadotrophins, suggesting that the regulated form of nitric oxide synthase (iNOS) is present. The objectives of the present study were to gain insight into the expression and role of iNOS in the follicle. Messeng...
Article
Understanding the paracrine events that regulate fertility in the cow is necessary not only because of the agricultural importance of this species, but also its potential use as a model for humans. Nitric oxide (NO), a free-radical gas, has been implicated in follicular growth in rodents, but the cow is an intriguing enigma: NO is produced by bovin...
Article
Full-text available
Fibroblast growth factors (FGF) are involved in paracrine signaling between cell types in the ovarian follicle. FGF8, for example, is secreted by oocytes and controls cumulus cell metabolism. The closely related FGF18 is also expressed in oocytes in mice. The objective of this study was to assess the potential role of FGF18 in follicle growth in a...
Article
Understanding the paracrine events that regulate fertility in the cow is necessary not only because of the agricultural importance of this species, but also its potential use as a model for humans. Fibroblast growth factors (FGF) and their receptors are involved in the paracrine modulation of ovarian function. For example, FGF2, 7 and 10 inhibit es...
Article
Angiotensin II (AngII) has been shown to be involved in the regulatory mechanism of ovulation and oocyte nuclear and cytoplasmic maturation in cattle. In rats, AngII induces apoptosis in granulosa cells and atresia of antral follicles during follicular development. However, the angiotensin converting enzyme (ACE) mRNA expression increases at the en...
Article
To determine if initial cell plating density alters steroidogenesis and the E(2):P ratio in granulosa cells in long-term serum-free culture. Experimental study. Academic institution. Cattle of slaughterhouse origin. Culture of granulosa cells in vitro at different cell plating density. Steroid secretion was measured by RIA, mRNA levels were measure...
Article
Angiotensin II (AngII) is best known for its role in blood pressure regulation, but it also has some documented actions in the reproductive system. There are two AngII receptors, AT1 and AT2. The AT1 receptor mediates a number of well-known AngII effects on smooth muscle contraction, aldosterone secretion and blood pressure regulation, while the AT...

Citations

... [31] Yap/Taz [32] Lats1/Lats2 [33] Mst1/Mst2 [34] FAdE/Nr5a1-Cre [35] Fetal cortex Tracing fetal adrenocortical cells descendants [35,36] FAdE/Nr5a1-CreERT2 [35] Fetal cortex Prkar1a [37] Tracing fetal adrenocortical cells descendants [35,37] Nr5a1 eGFP-CreERt2 -AGP/fetal cortex, definitive cortex hCyp11a1-iCre [38] Fetal cortex/definitive cortex Insr/Igf1r [39] mCyp11a1-iCre [40] Fetal cortex/definitive cortex Ctnnb1 ex3 [41] Nr5a1 [40] Cyp11a1 Gfp,Cre/+ [42] Fetal cortex/definitive cortex AR [43,44] Akr1b7-Cre [45] Fetal cortex/definitive cortex Ctnnb1 ex3 [24,25,46,47] Prkar1a [25,26] Prkaca [25] Cyp11b2 Cre /AS Cre [48] Aldosterone producing zG cells and their zF descendants ...
... The Hippo pathway is reported to regulate the balance between GC proliferation (which dominates before ovulation when Hippo is predominantly inactive), steroidogenesis, and differentiation of the cells into a luteal phase (processes that dominate after ovulation when Hippo is active) [14,47]. The Hippo pathway effectors interact with the EGF-like signaling [51], as well as the components of the aforementioned intracellular signaling involving mTOR [12,14,52]. Excessive inhibition of the Hippo pathway and unrestrained inflow of the chief final mediators YAP-1 and TAZ into the nucleus have been involved in the development of PCOS [46,53], endometriosis [54,55], and ovarian tumorigenesis [56]. ...
... Furthermore, many neuroregulatory substances have been demonstrated to be related to the Hippo pathway and involved in various physiological functions. The Hippo pathway participates in the luteinizing hormone [40] and gonadotropin-releasing hormone [41] secretion in gonadotrope cells. The neuropeptide Galanin contributes to cholangiocyte proliferation through activation of the Hippo pathway [42]. ...
... The discrepancies could be explained by differences in cell culture conditions, methods used to manipulate Yap1/Taz expression, the nature of the agonists that were used and the duration of treatments. Pretreatment of bovine mural GCs with verteporfin (VP), an inhibitor of YAP1-TEAD interaction [55], was shown to prevent the upregulation of Ereg by LH [56]. This difference might be explained by a greater role of Ereg (and a lesser role for Areg) in the acute response of bovine mural GCs to LH [57]. ...
... Secreted Frizzled Related Protein 4 (SFRP4) inhibits Wnt signaling, a pathway known to play multiple functions during folliculogenesis (Hernandez Gifford, 2015). The role of SFRP4 during folliculogenesis remain under debate, as its ablation in mice has been reported to increase (Zamberlam et al., 2019) or decrease (Christov et al., 2011) litter size, and whereas mRNA content in human cumulus cells was positively associated with in vivo meiotic progression (Devjak et al., 2012), protein content in human follicular fluid has been negatively associated with in vitro meiotic progression (Pla et al., 2021). The differences between studies may be linked to the different hormonal environment of in vitro and in vivo maturation, as SFRP4 expression is modulated by LH in a species-specific manner (Maman et al., 2011). ...
... It also includes the syndromes of abnormal hormone sources, abnormal hormone receptors, and physiological disorders caused by the abnormal metabolism of hormones or substances. In the endocrine system, H 2 S can act on the thyroid (10), adrenal gland (11), and gonad (12) through the hypothalamus-pituitary axis, as well as on the pancreas (13), thereby participating in the regulation of many hormones in the body, and the hypothalamuspituitary axis can, in turn, regulate the production of H 2 S (14). ...
... Wnt5a/β-catenin signaling is critical in estrogenmediated uterine development [5]. It can be induced by estradiol [6], participating in the development and functional maintenance of the endometrium [7,8] and modulating the self-renewal activity of endometrial mesenchymal stem cells (eMSCs) [9][10][11], indicating that it might be a potential target in IUA treatment. ...
... Saralasin also inhibits cyclin D2 (regulates GCs proliferation between G1 and S stage) which leads to poor follicular growth and development in cattle (Quirk et al., 2006). Moreover, intrafollicular administration of Ang II or AT2R agonist rescues the second largest follicle from atresia (Ferreira et al., 2009;Goncalves et al., 2010). These findings suggest that Ang II and its receptor are involved in follicular growth, maturation and dominance. ...
... In cattle, Ang II type 2 receptor was identified mainly in the dominant follicle by autoradiograms (Schauser et al. 2001), and its expression was positively correlated with follicular diameter (Nielsen et al. 1994). Recently, our group demonstrated that expression of AT 2 mRNA in granulosa cells is correlated with follicle health and estradiol content and is regulated by follicle-stimulating hormone (FSH), insulin-like growth factor-I, bone morphogenetic protein-7, fibroblast growth factor (FGF-7), and FGF-10 (Portela et al. 2006, Portela et al. 2007. We also showed that Ang II regulates protease nexin-1 (PN-1; inhibitor of proteases involved in extracellular matrix remodeling and follicle rupture) in granulosa cells via AT 2 receptor in cattle (Portela et al. 2006). ...
... In this study, Wnt family member 5A (WNT5A) is involved in the Wnt signaling pathway, which is related to spermatogenesis, epididymal sperm maturation, and embryonic sexual development [52][53][54][55]. WNT5A was proved to be a key regulator of follicle development and gonadotropin responsiveness [56,57]. The vertebrate limb is a classical model for understanding the patterning of three-dimensional structures during embryonic development. ...