Age-dependent vulnerability of the ovary to AhR-mediated TCDD action before puberty: Evidence from mouse models.

In female mammals, puberty and fertility are regulated by the synthesis of estradiol (E2) by the ovaries at the infantile stage and at the approach of puberty, a process which may be affected by endocrine disrupting chemicals (EDC)s acting through the Aryl hydrocarbon receptor (AhR). However, there is no information on AhR-mediated regulation of ovarian estrogenic activity during these developmental periods. Here, we assessed in mouse models, the intrinsic and exogenous ligand-induced AhR action on E2 synthesis at the infantile stage (14 days postnatal (dpn)) and at the approach of puberty (28 dpn).

A novel action of follicle-stimulating hormone in the ovary promotes estradiol production without inducing excessive follicular growth before puberty.

In cyclic females, FSH stimulates ovarian estradiol (E2) production and follicular growth up to the terminal stage. A transient elevation in circulating FSH and E2 levels occurs shortly after birth. But what could be the action of FSH on the ovary during this period, and in particular how it stimulates ovarian steroidogenesis without supporting terminal follicular maturation is intriguing.

Rat Gnrhr promoter directs species-specific gene expression in the pituitary and testes of transgenic mice.

The GnRH receptor (GnRHR) is expressed in several non-pituitary tissues, notably in gonads. However, mechanisms underlying the gonad-specific expression of Gnrhr are not well understood. Here, Gnrhr expression was analysed in the developing testes and pituitaries of rats and transgenic mice bearing the human placental alkaline phosphatase reporter gene (ALPP) under the control of the rat Gnrhr promoter.

Reporter transgenic mouse models highlight the dual endocrine and neural facet of GnRH receptor function.

In the pituitary of mammals, the GnRH receptor (GnRHR) plays crucial roles in the neuroendocrine control of reproductive function. This receptor is specifically expressed by the gonadotrope cells scattered among the five other endocrine cell types constituting the anterior pituitary; it is also expressed in other organs, such as the gonads and brain where its function is not well defined. To gain insight into GnRHR function, distribution, and regulation, several transgenic approaches have been developed using a range of reporter genes under the control of the mouse, rat, or ovine GnRHR gene (Gnrhr) promoters.

GnRH receptor gene expression in the developing rat hippocampus: transcriptional regulation and potential roles in neuronal plasticity.

In the pituitary of mammals, the GnRH receptor (GnRHR) plays a primary role in the control of reproductive function. It is further expressed in the hippocampus, where its function, however, is not well defined. By quantitative RT-PCR analyses, we demonstrate herein that the onset of GnRHR gene (Gnrhr) expression in the rat hippocampus was unexpectedly delayed as compared to the pituitary and only occurred after birth.

The GnRH receptor and the response of gonadotrope cells to GnRH pulse frequency code. A story of an atypical adaptation of cell function relying on a lack of receptor homologous desensitization.

Brain control of the reproductive system is mediated through hypothalamic gonadotropin-releasing hormone (GnRH) which activates specific receptors (GnRHR) present at the surface of the pituitary gonadotropes to trigger secretion of the two gonadotropins LH and FSH. A unique feature of this system is the high dependence on the secretion mode of GnRH, which is basically pulsatile but undergoes considerable fluctuations in pulse frequency pattern in response to endogenous or external factors. How the physiological fluctuations of GnRH secretion that orchestrate normal reproduction are decoded by the gonadotrope cell machinery to ultimately control gonadotropin release and/or subunit gene transcription has been the subject of intensive studies during the past decades.

OVEX1, a novel chicken endogenous retrovirus with sex-specific and left-right asymmetrical expression in gonads.

Background: In chickens, as in most birds, female gonad morphogenesis is asymmetrical. Gonads appear first rather similarly, but only the left one undergoes full differentiation and gives rise to a functional ovary. The right gonad, in which the cortex does not develop, remains restricted to the medulla and finally regresses.

Sex-specific expression of SOX9 during gonadogenesis in the amphibian Xenopus tropicalis.

To investigate the role of SOX9 gene in amphibian gonadogenesis, we analyzed its expression during male and female gonadogenesis in Xenopus tropicalis. The results showed that in both sexes SOX9 mRNA and protein were first detectable after metamorphosis when the gonads were well differentiated and remained present until the adult stage. In the testis, SOX9 expression was restricted to the nucleus of Sertoli-like cells, similarly to what has been observed in other vertebrates suggesting a conserved role in vertebrate testicular differentiation.

Early aspects of gonadal sex differentiation in Xenopus tropicalis with reference to an antero-posterior gradient.

In an effort to contribute to the development of Xenopus tropicalis as an amphibian model system, we carried out a detailed histological analysis of the process of gonadal sex differentiation and were able to find evidence that gonadal differentiation in X. tropicalis follows an antero-posterior gradient. Although the main reason for the presence of a gradient of sex differentiation is still unknown, this gradient enabled us to define the early events that signal ovarian and testicular differentiation and to identify the undifferentiated gonad structure.

What is the role of PACAP in gonadotrope function?

Strong evidence in favor of a direct action of hypothalamic PACAP at the pituitary to modulate gonadotrope function has been acquired mainly by in vitro studies using cultured pituitary cells or gonadotrope cell lines. In particular, PACAP has been shown to cooperate with GnRH, the primary regulator of gonadotropes, to regulate/modulate gonadotropin subunit gene expression, gonadotropin release as well as gonadotrope responsiveness. These effects of PACAP appear to be due essentially to its high potent stimulatory action on the cAMP/protein kinase pathway.

Consequences of fetal irradiation on follicle histogenesis and early follicle development in rat ovaries.

Follicle histogenesis, in which follicles arise from fragmenting ovigerous cords, is a poorly understood mechanism that is strictly dependent upon the presence of germ cells. Our previous studies have shown that severely germ cell-depleted rat ovaries after fetal gamma-irradiation display modifications of follicular endowment and dynamics during the immature period. The primordial follicle stock was absent and the follicles with primary appearance remained quiescent longer than in control ovaries during the neonatal period.

Contribution of germ cells to the differentiation and maturation of the ovary: insights from models of germ cell depletion.

In mammals, the role played by germ cells in ovarian differentiation and folliculogenesis has been the focus of an increasing number of studies over the last decades. From these studies, it has emerged that bidirectional communication between germ cells and surrounding companion cells is required as soon as the initial assembly of follicles. Models of germ cell depletion that arise from both spontaneous and experimentally induced mutations as well as irradiation or chemical treatments have been helpful in deciphering the role played by germ cells from the onset of ovarian differentiation onward.

Gonadotropin-releasing hormone and the control of gonadotrope function.

Normal gametogenesis and steroidogenesis is highly dependent on the pulsatile release of hypothalamic GnRH that binds high-affinity receptors present at the surface of pituitary gonadotrophs thereby triggering the synthesis and release of the gonadotropins LH and FSH. The mammalian GnRH receptor displays the classical heptahelical structure of G protein-coupled receptors with, however, a unique feature, the lack of a C-terminal tail. Accordingly, it does not desensitise sensu stricto, and internalises very poorly.

Follicular cells acquire sertoli cell characteristics after oocyte loss.

Although it has been suggested that in mammals the loss of female germ cells may induce the masculinization of the ovarian compartment, there has been as yet no conclusive demonstration. To directly address that question, the present study has been designed to determine the fate of follicular cells after oocyte loss. Using gamma-irradiation to selectively deplete oocytes in nongrowing follicles in female rats, we show that follicular cells in oocyte-depleted follicles survive, proliferate, and subsequently acquire morphological characteristics of Sertoli cells: elongated cytoplasm, basal location of the nucleus, and specific Sertoli cell junctions, the ectoplasmic specializations.

Basal membrane remodeling during follicle histogenesis in the rat ovary: contribution of proteinases of the MMP and PA families.

In mammalian females, follicular units arise from the fragmentation of ovigerous cords, which spread over the first three postnatal days in the rat. The mechanisms underlying such a process of epithelial remodeling involve a specific balance between basal membrane (BM) deposition and degradation that has as yet not been precisely described. We have investigated the contribution of proteases in BM remodeling by localization of transcripts, protein, or enzymatic activity.

[An ambiguous role of steroidogenic factor 1 in the rat GnRH receptor gene expression. Lessons from transgenic mice].

Because the GnRH receptor plays a paramount role within the reproductive axis, the understanding of the molecular apparatus that governs the tissue-specific expression and regulation of this gene must lead to a better knowledge of the physiology and the physiopathology of the gonadotrope function. To elucidate these mechanisms, we have used two complementary in vivo and in vitro approaches. Firstly, we have isolated the pituitary promoter of the rat GnRH receptor gene and investigated its activity using transient transfection into two gonadotrope-derived cell lines, the alphaT3-1 and the LbetaT2 cell lines.

The promoter of the rat gonadotropin-releasing hormone receptor gene directs the expression of the human placental alkaline phosphatase reporter gene in gonadotrope cells in the anterior pituitary gland as well as in multiple extrapituitary tissues.

Previous studies dealing with the mechanisms underlying the tissue-specific and regulated expression of the GnRH receptor (GnRH-R) gene led us to define several cis-acting regulatory sequences in the rat GnRH-R gene promoter. These include functional sites for steroidogenic factor 1, activator protein 1, and motifs related to GATA and LIM homeodomain response elements as demonstrated primarily in transient transfection assays in mouse gonadotrope-derived cell lines. To understand these mechanisms in more depth, we generated transgenic mice bearing the 3.

Unaltered development of the initial follicular waves and normal pubertal onset in female rats after neonatal deletion of the follicular reserve.

In rats, the pool of primordial follicles is established within the first 3 d postnatally (dpn). Immediately after their differentiation, a subset of follicles begins to grow and constitutes the initial follicular waves. In this study we investigated the development of these early growing follicles after deletion of the primordial follicle pool induced by 1.

Differential expression of tissue inhibitor of metalloproteinases type 1 (TIMP-1) during mouse gonad development.

In mammals, the gene Sry initiates signaling pathways triggering the differentiation of a testis from a sexually indifferent gonad. Assuming that these morphogenetic events may alter the proteolytic balance, the expression of matrix metalloproteinases (MMPs) and inhibitors (TIMPs) was investigated in gonads from 11.5 days postcoitum (dpc) onward, when testicular organogenesis occurs.

Establishment of the reproductive function and transient fertility of female rats lacking primordial follicle stock after fetal gamma-irradiation.

In mammals, the primordial follicle stock is not renewable, and its size, therefore, limits the reproductive life span of the female. In this study we have investigated the morphological and functional differentiation of dysgenesic ovaries in female rats exposed in utero to 1.5 Gy gamma-irradiation.

Different patterns of anti-Müllerian hormone expression, as related to DMRT1, SF-1, WT1, GATA-4, Wnt-4, and Lhx9 expression, in the chick differentiating gonads.

In mammals, anti-Müllerian hormone (AMH) is produced by Sertoli cells from the onset of testicular differentiation and by granulosa cells after birth. In birds, AMH starts to be expressed in indifferent gonads of both sexes at a similar level and is later up-regulated in males. We previously demonstrated that, unlike in mammals, the onset of AMH expression occurs in chick embryo in the absence of SOX9.