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

Publications (34)

Preprint
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Background Secreted frizzled-related proteins (SFRPs) comprise a family of WNT signaling antagonists whose roles in the ovary are poorly understood. Sfrp4-null mice were previously found to be hyperfertile due to an enhanced granulosa cell response to gonadotropins, leading to decreased antral follicle atresia and enhanced ovulation rates. The pres...
Article
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Recent reports suggest that the Hippo signaling pathway regulates testis development, though its exact roles in Sertoli cell differentiation remain unknown. Here, we examined the functions of the main Hippo pathway kinases, large tumor suppressor homolog kinases 1 and 2 (Lats1 and Lats2) in developing mouse Sertoli cells. Conditional inactivation o...
Article
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Simple Summary Cystic ovarian disease is an important ovarian disorder that leads to anovulatory infertility in dairy cows. In the present study, we used spontaneous ovarian follicular cysts to show the first evidence that the deregulation of Hippo pathway effector yes-associated protein expression and/or activity can be a potential key to better u...
Article
Ovulatory disorders are a major cause of infertility in humans as well as economically important species. In physiological conditions, the LH surge induces the expression of epidermal growth factor (EGF)-like ligands that activate the EGR receptor (EGFR) and subsequently the mitogen-activated protein kinase (MAPK) pathway. The magnitude and duratio...
Article
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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
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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
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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
Full-text available
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
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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
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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
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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
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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

... Mechanistically, DUSP16 impedes JNK and p38 activation, thereby attenuating BAX accumulation within mitochondria and subsequently retarding apoptosis progression [27]. In mice, DUSP1 (MKP-1) exerts a negative regulatory role in immune cells and is closely associated with the immune response and inflammation [28]. Simultaneously, DUSP16 also participates in the regulation of nervous system development and embryonic development [29]. ...
... Among other things, they discovered that the adrenal gland of the dog has an intrinsic osmosensitivity [19, 21-23, 31, 32]. A number of transgenic mouse models have been developed to study the development and pathophysiology of the adrenal gland [1,2,4,6,12,15]. The phenotype of these mice is usually studied at the animal level using in vivo methods, clinical chemistry methods, histologic techniques, fresh adrenal gland slices, and primary cultures. ...
... 29 More recently, we also showed that inactivation of Lats1 and Lats2 in fetal Leydig and Sertoli cells of the developing testis impairs testicular development. 30 However, this model could not determine whether the abnormal phenotype observed in Sertoli cells and fetal Leydig cells resulted from a direct effect of Lats1/2 inactivation in these cells, an indirect effect of these cell populations on each other, or more likely, a combination of both. ...
... YAP1/TAZ has been revealed to regulate ovulation in bovines [15], be associated with pregnancy recognition and establishment in ewes [31], and be involved in embryonic development in cows [32]. These studies have opened the prelude to the study of YAP1/TAZ in ruminants. ...
... [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 ...
... A number of studies indicate the importance of Hippo effectors to ovarian physiology in adult animals, including cattle [14][15][16]. Interestingly, it has been shown that overexpression of YAP negatively impacts LH action in mouse granulosa cells (GCs) [17] and that YAP is considered a susceptibility gene for polycystic ovarian syndrome in women [18,19]. ...
... Inhibition of the Hippo signaling pathway inhibits GnRHinduced ovulation in cattle, indicating that this pathway indeed plays a crucial role in animal ovulation [36]. Additionally, the Hippo signaling pathway might regulate the secretion of luteinizing hormone in the mouse pituitary gland, consequently regulating the reproductive process in mice [37]. ...
... GA and VP are commonly used to investigate the functions of YAP1/TAZ in various developmental processes or tumor progressions, such as the proliferation of ovarian cancer cells [12], the reprogramming of colonic epithelium [13], and the homeostasis and repair of skin epithelium [14]. In addition, VP has been successfully used to inhibit YAP1 activity in bovine preovulatory granulosa cells [15]. Thus, GA and VP could be proper tools for studying the function of YAP1/TAZ in RE cell proliferation. ...
... Female reproductive factors, such as ovarian development, oocyte maturation, estrous cycle, and embryo implantation, were influenced primarily by sex hormones, including progesterone, prostaglandin, and estrogen (Innocenti et al., 2017;Bui et al., 2022). Sex hormones play crucial roles in the complex and interconnected processes of pregnancy and childbirth (Zamberlam et al., 2019). Fat could affect the synthesis of cholesterol, which is the precursor of sex hormones (Fox et al., 2009). ...
... Furthermore, inhibition of CTH activity can reduce the ovulation rate in mice. 17 And CTH mRNA has also been reported in porcine cumulus cells and oocytes. 18 Moreover, a decrease in CTH activity may also lead to placental abnormalities in pre-eclampsia and fetal growth restriction. ...