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PubMed2004

Using real time RT-PCR analysis to determine multiple gene expression patterns during XX and XY mouse fetal gonad development.

New techniques are being applied to identify all the genes involved in mammalian gonad development and differentiation. As this list of genes increases, understanding the potential interactions between these genes will become increasingly difficult. We used a real time reverse transcription PCR (real time RTPCR) protocol to examine and compare the relative expression levels of 55 genes in individual mouse fetal gonads. Real time PCR analysis demonstrated that except for Sry, no differences in relative gene expression were detectable between XX and XY gonad/mesonephroi complexes at embryonic day (E)11.5. Following Sry peak expression at E11.5, a number of genes were expressed at significantly higher relative levels in E12-14 XY than XX gonads. Of six genes expressed at higher levels in E12.5-14 XX than XY gonads, three, Bmp2, Emx2, and Fgfr2, had not been reported previously. Our results caution that differential localization patterns observed with whole mount in situ hybridization techniques may not accurately reflect changes in transcript levels. We conclude that real time PCR is an efficient and powerful tool for studying multiple gene expression patterns during gonad development and differentiation, and can provide insight into gene interactions.

Animals↗

PubMed1985

Gonadal development and fertility of mice treated prenatally with cadmium during the early organogenesis stages.

Gonadal development was studied in mouse embryos that were exposed to cadmium during the early organogenesis stages. At 13.5 days, both the male and the female embryos had small genital ridges. Fewer primordial germ cells were found in the male embryos. In both sexes, many primordial germ cells were left outside the genital ridges, presumably as a result of retarded cell migration. In 16.5-day embryos, the size of the testes and ovaries and the number of differentiating germ cells were reduced. Many germ cells degenerated during the differentiation to spermatogonia and meiotic oocytes. The perturbed gonadal development was less likely to be caused primarily by a defective hypothalamopituitary axis but was more a part of the general cadmium-induced damage. The fertility of the male offspring was impaired by the prenatal cadmium insult, but the females were apparently fertile. The epididymal spermatozoa of the cadmium-affected offspring showed a lower fertilizing capacity in vitro. The impaired fertility of the cadmium-affected mice was the result of poor gonadal growth, paucity of germ cells, and defective maturation of the gametes.

Abnormalities, Drug-Induced↗

PubMed2003

Gonad development characteristics and sex ratio in triploid Chinese shrimp ( Fenneropenaeus chinensis).

This paper details for the first time the gonad development characteristics and sex ratio of triploid shrimp ( Fenneropenaeus chinensis). In triploid shrimp the development of gonad is apparently impaired, especially in females. In the ovary of triploids, germ cells mainly remain at oogonia stage during September through December. From January to February of the next year, partial primary oocytes developed in the ovary lobes. Spermatocytes and spermatids could be observed in the testes of triploids, and a few sperm were observed in the vas deferens and spermatophores. The morphology of sperms in triploid shrimp was abnormal. Flow cytometry was used to detect the ploidy of sperm in the vas deferens. The data showed that triploidy could affect the sex ratio in Chinese shrimp. The female-to-male ratio in triploids of about 4:1 will favor triploid shrimp aquaculture.

Animals↗

PubMed1996

Bioactivation of Müllerian inhibiting substance during gonadal development by a kex2/subtilisin-like endoprotease.

During male gonadal development Müllerian duct regression is mediated by the actions of the hormone Müllerian inhibiting substance (MIS), a member of the transforming growth factor beta superfamily. MIS is considered to be unique among members of this superfamily because bioactivation of MIS via proteolytic processing is hypothesized to occur at its target organ, the Müllerian duct. We find instead that the majority of MIS is processed and secreted from the embryonic testes as a complex in which the mature region remains noncovalently associated with the prodomain. In addition, we have identified two candidate endoproteases that are expressed in the testes and that may be capable of processing MIS in vivo. These kex2/subtilisin-like enzymes, PC5 and furin, are members of the proprotein convertase family that have been implicated in hormone bioactivation via proteolytic processing after dibasic amino acid cleavage recognition sites. Coexpression of PC5 and MIS in transfected mammalian cells results in efficient processing and bioactivation of MIS. Our results suggest that MIS is a natural substrate for PC5, thereby supporting a role for prohormone convertases in the activation of transforming growth factor beta-related hormones during development.

Animals↗

PubMed1991

Correlation of annual change of luteinizing hormone-releasing hormone (LH-RH) with gonadal development in amphioxus.

The present study demonstrates for the first time by RIA that LH-RH is present in the heads as well as the bodies of the amphioxuses of both sexes. Gonadoliberin increases gradually during the course of gonadal development. At the time of gonadal maturity, LH-RH content reaches a maximum. The annual change of LH-RH correlates well with gonadal development and the gonadosomatic index (GSI). The reproductive season of the amphioxus covers about three months from May to July, and LH-RH content starts to increase in May (66.89 +/- 5.26 ng) and reaches the peak in June (158.57 +/- 3.17 ng), indicating that LH-RH is likely also to be involved in the reproductive activity of the chordate. This finding is of significance in understanding the evolutionary process of the reproductive endocrine in the vertebrate.

Animals↗

PubMed2004

lin-35/Rb and xnp-1/ATR-X function redundantly to control somatic gonad development in C. elegans.

In screens for genetic modifiers of lin-35/Rb, the C. elegans retinoblastoma protein (Rb) homolog, we have identified a mutation in xnp-1. Mutations in xnp-1, including a presumed null allele, are viable and, in general, appear indistinguishable from the wild type. In contrast, xnp-1 lin-35 double mutants are typically sterile and exhibit severe defects in gonadal development. Analyses of the abnormal gonads indicate a defect in the lineages that generate cells of the sheath and spermatheca. xnp-1 encodes the C. elegans homolog of ATR-X, a human disease gene associated with severe forms of mental retardation and urogenital developmental defects. xnp-1/ATR-X is a member of the Swi2/Snf2 family of ATP-dependent DEAD/DEAH box helicases, which function in nucleosome remodeling and transcriptional regulation. Expression of an xnp-1 Colon, two colons GFP promoter fusion is detected throughout C. elegans development in several cell types including neurons and cells of the somatic gonad. Our findings demonstrate a new biological role for Rb family members in somatic gonad development and implicate lin-35 in the execution of multiple cell fates in C. elegans. In addition, our results suggest a possible conserved function for xnp-1/ATR-X in gonadal development across species.

Animals↗

PubMed2026

Genomic identification and functional characterization of the nuclear receptor gene family in relation to sex determination and gonad development in the Pacific oyster (Crassostrea gigas).

Nuclear receptors (NRs) are a large superfamily of transcription factors that control a wide range of physiological processes by modulating the expression of downstream target genes. Numerous studies have confirmed that NR family members play critical and conserved roles in sex determination and gonadal development across metazoans. However, in mollusks, systematic characterization of NRs and their potential functions in gonadal regulation remain largely unexplored. In this study, 46 NR gene family members in the Pacific oyster (Crassostrea gigas) were identified and assigned to eight subfamilies. All NR family members contain at least one of the two core domains (DNA-binding domain, DBD; ligand-binding domain, LBD), and conserved exon-intron structures were observed within the same subgroup, indicating their evolutionary conservation. Furthermore, expression profiling revealed high expression of CgNR2F, CgNR5A1-1, and CgNR0B1 in undifferentiated gonads, suggesting their potential involvement in sex determination. CgNR1A and CgNR2E5 were specifically expressed in female gonads and exhibited female-biased expression patterns, indicating a putative role in ovarian development. Moreover, CgNR3A and CgNR3B showed high expression levels during the undifferentiated stage and early male development stage, implying their possible participation in male gonadal development and gametogenesis. These results expand the understanding of the NR gene family in C. gigas and help elucidate the potential functions of NR genes in sex determination and gonadal development.

Animals↗

PubMed1995

Preliminary evidence suggesting variations of GtH 1 and GtH2 mRNA levels at different stages of gonadal development in rainbow trout, Oncorhynchus mykiss.

To study the variations of alpha and beta GtH 1 and 2 gene expression during gonadal development in male and female rainbow trout, chum salmon alpha and beta GtH 1 and 2 probes were used. The alpha subunit cDNA probe used is identical to the cDNA encoding the alpha subunit common to both GtH 1 and 2. Total RNAs were prepared from pooled pituitaries and the validation of the use of these probes for studying the variation of GtH mRNAs was made by Northern blot analysis. The quantitative determination of GtH mRNAs employed slot blot hybridization. In males and females, beta GtH 1 predominates in early stages of gonadal development (spermatogonia A and previtellogenesis), beta GtH 2 being weakly expressed. Both beta GtH 1 and beta GtH 2 are expressed during prespermiation, spermiation, and the periovulatory period with a predominance of beta GtH 2. In both sexes alpha GtH variations follow beta GtH 2 variations.

Animals↗

PubMed1989

Pineal and ocular influences on male and female turkeys: plasma luteinizing hormone and prolactin levels during gonadal development.

Plasma levels of prolactin (PRL) and luteinizing hormone (LH) were determined in pinealectomized (PX) and/or bilateral ocular enucleated (EX) turkey hens and toms during gonadal development. Measurements were obtained weekly for 6 weeks following photo-induced ovarian recrudescence in adult hens and biweekly from 12 to 34 weeks of age in sexually developing toms. Both hens and toms were maintained on a photoperiod of 16L:8D. Plasma PRL levels were significantly correlated with time (P less than 0.01) and were linear with significant slopes (P less than 0.01) in all treatment groups of hens and toms. However, the regression coefficients were positive for the hens and negative for the toms. Both PX and EX reduced PRL levels in the hens. PX did not significantly affect PRL levels of toms but EX depressed PRL levels. In hens LH was not correlated with weeks of photostimulation but in toms LH was positively correlated to age and linear with significant slopes in all treatment groups. There were no significant treatment effects on plasma LH levels of hens or toms. It was concluded that neither the pineal gland nor the eyes affect plasma LH levels of male turkeys during testicular development or female turkeys during photostimulated ovarian recrudescence. Although the eyes affected plasma PRL of both males and females during gonadal development, the pineal only influenced female PRL levels.

Animals↗

PubMedDate not supplied

Signaling at the crossroads of gonad development.

In mammals, the gonads arise as bipotential primordia that are capable of developing as either testes or ovaries. Expression of the Y-linked gene Sry in the XY gonad initiates testis differentiation; in the absence of Sry, ovarian pathways prevail. Although the molecular targets of SRY are not known, many of the early cellular and morphological events that occur downstream of Sry have been characterized. These include increased cell proliferation, Sertoli cell differentiation, testis cord formation, development of a testis-specific vasculature and differentiation of interstitial lineages. Recently, several of the molecular signals that direct these processes have been identified. In addition, the pathways that suppress features of testis development in the XX gonad are being elucidated.

Animals↗

PubMed1999

Expression of steroidogenic factor 1 and Wilms' tumour 1 during early human gonadal development and sex determination.

The transcription factors SF-1 and WT1 play pivotal roles in mammalian gonadal development and sexual differentiation. In human embryos, both SF-1 and WT1 are expressed when the indifferent gonadal ridge first forms at 32 days post-ovulation. As the sex cords develop - providing morphological evidence of testis differentiation - SF-1 localises predominantly to developing Sertoli cells in the sex cords, whereas WT1 retains a broader pattern of expression. Later, SF-1 localises predominantly to steroidogenic Leydig cells, and WT1 localises to the sex cords. In the ovary, SF-1 and WT1 transcripts persist in the gonadal ridge from the earliest developmental stages throughout the critical period of sex determination. These studies, which delineate for the first time the sequential expression profiles of SF-1 and WT1 during human gonadal development, provide a framework for understanding human sex reversal phenotypes associated with their mutations.

DNA-Binding Proteins↗

PubMed2001

Genes essential for early events in gonadal development.

The acquisition of a sexually dimorphic phenotype is a critical event in mammalian development. The basic underlying principle of sexual development is that genetic sex--determined at fertilization by the presence or absence of the Y chromosome--directs the embryonic gonads to differentiate into either testes or ovaries. Thereafter, hormones produced by the testes direct the developmental program that leads to male sexual differentiation. In the absence of testicular hormones, the female pathway of sexual differentiation occurs. Recent studies have defined key roles in gonadal development for two transcription factors: Wilms' tumor suppressor 1 (WT1) and steroidogenic factor 1 (SF-1). After presenting a brief overview of gonadal development and sexual differentiation, this chapter reviews the studies that led to the isolation and characterization of WT1 and SF-1, and then discusses how interactions between these two genes may mediate their key roles in a common developmental pathway.

Animals↗

PubMed1986

Effect of a mercurial fungicide on the gonadal development of the teleostean fish Channa punctatus (Bloch).

Channa punctatus exposed to a "safe" concentration of 0.20 ppm of a commercial mercurial fungicide, Emisan (MeEHgCl), for 6 months, from January to June, exhibited significant inhibition of gonadal development as evidenced by their histology and reduced gonadosomatic index. Degenerative changes were also evident. Correlative histological changes were also noted in the pituitary gonadotrophs which were reduced in the exposed fish. Several stage I oocytes exhibited proteinaceous extra and intranuclear "inclusion bodies," and intranuclear "ring-like bodies" associated with the ultimate degeneration of the oocytes. These observations suggest that MeEHgCl inhibits gonadal development through the hypothalamic-pituitary-gonadal axis in this species.

Animals↗

PubMed2004

Minireview: transcriptional regulation of gonadal development and differentiation.

The embryonic gonad is undifferentiated in males and females until a critical stage when the sex chromosomes dictate its development as a testis or ovary. This binary developmental process provides a unique opportunity to delineate the molecular pathways that lead to distinctly different tissues. The testis comprises three main cell types: Sertoli cells, Leydig cells, and germ cells. The Sertoli cells and germ cells reside in seminiferous tubules where spermatogenesis occurs. The Leydig cells populate the interstitial compartment and produce testosterone. The ovary also comprises three main cell types: granulosa cells, theca cells, and oocytes. The oocytes are surrounded by granulosa and theca cells in follicles that grow and differentiate during characteristic reproductive cycles. In this review, we summarize the molecular pathways that regulate the distinct differentiation of these cell types in the developing testis and ovary. In particular, we focus on the transcription factors that initiate these cascades. Although most of the early insights into the sex determination pathway were based on human mutations, targeted mutagenesis in mouse models has revealed key roles for genes not anticipated to regulate gonadal development. Defining these molecular pathways provides the foundation for understanding this critical developmental event and provides new insight into the causes of gonadal dysgenesis.

Animals↗

PubMedDate not supplied

Prenatal ethanol exposure: effects on androgen and nonandrogen dependent behaviors and on gonadal development in male rats.

Prenatal exposure to alcohol may impair gonadal and behavioral development in male rats, possibly via reduction of perinatal androgenization. We examined locomotor activity on postnatal day 18 (PND 18), which is not influenced by perinatal androgens and juvenile play and testicular development (testes weight), which are dependent on perinatal androgen exposure, in rats whose dams consumed ethanol during pregnancy. Male offspring of pair-fed and lab chow-fed dams served as controls. Despite reduced anogenital distance at birth, indicating compromised perinatal androgenization, fetal ethanol-exposed males did not exhibit demasculinization of play behavior. Hyperactivity in fetal ethanol-exposed males indicated that the treatment regimen was sufficient to produce behavioral deficits. Testes weight was reduced in both ethanol-exposed and pair-fed offspring, indicating that nutritional deficits associated with maternal ethanol intake may impair normal gonadal development in male rats. The findings suggest that fetal ethanol exposure may influence gonadal development but not necessarily affect a gonadal hormone-dependent behavior.

Androgens↗

PubMed1999

Genes essential for early events in gonadal development.

The acquisition of a sexually dimorphic phenotype is a critical event in mammalian development. The basic underlying principle of sexual development is that genetic sex-determined at fertilization by the presence or absence of the Y chromosome--directs the embryonic gonads to differentiate into either testes or ovaries. Thereafter, hormones produced by the testes direct the developmental program that leads to male sexual differentiation. In the absence of testicular hormones, the female pathway of sexual differentiation occurs. Recent studies have defined key roles in gonadal development for two transcription factors: Wilms' tumor suppressor 1 (WT1) and steroidogenic factor 1 (SF-1). After presenting a brief overview of gonadal development and sexual differentiation, this paper reviews the studies that led to the isolation and characterization of WT1 and SF-1, and then discusses how interactions between these two genes may mediate their key roles in a common developmental pathway.

Animals↗

PubMed2000

Branchial Na(+)K(+)ATPase activity in brook charr (Salvelinus fontinalis): effect of gonadal development in hypo- and hyperosmotic environments.

Changes in gill Na(+)K(+)ATPase activity were examined following the transfer of brook charr (Salvelinus fontinalis) from fresh water (FW) to seawater (SW). Gonadal development was altered at the hatching stage using three doses of ionizing radiation (IR): 6.2, 7.8, and 11.4 Gray (Gy). A non-irradiated control group was also included in the experimental set-up. Following 15 and 19 months of growth in FW, assessment of gill activity in regard to gonadal status (sterile vs. mature) and level of IR exposure was realized by conducting two estuarine challenge tests. A first introduction was performed during June (period of highest osmoregulatory capacities for this species) (summer experiment). A second introduction was conducted during October (period of diminished osmoregulatory capacities) (fall experiment). Gill Na(+)K(+)ATPase activity and water content were measured at different times and two FW control samplings were added in October and January. In the summer experiment (June-December), normal gonadal development of female brook charr was related to reduced gill Na(+)K(+)ATPase activity during the spawning period as compared to sterile fish (4.0+/-1.5 and 7.2+/-1.9 micromole Pi. mg protein(-1). hr(-1)) (P<0.0002). Similar results were not observed in FW conditions, implying that a lack of gonadal growth does not initiate a significant advantage when the osmoregulatory system including the gills are not highly in demand, i.e. in a FW environment. Ionizing radiation exposure of < or =11.4 Gy at the hatching stage had no significant negative or positive effect on Na(+)K(+)ATPase activity either in FW or SW conditions.

Adaptation, Physiological↗

PubMed2002

Disrupting effects of polychlorinated biphenyls on gonadal development and reproductive functions in chickens.

Polychlorinated biphenyls (PCBs) are worldwide persistent pollutants that have produced detrimental effects on endocrine function and reproduction in a variety of species. The present study revealed effects of PCBs on gonadal development and functions in chickens of different ages. Aroclor 1254 (0-100 microg/egg) was injected into Hyline chicken eggs before incubation. The adult chickens received Aroclor 1254 by gavage (50 mg/kg BW). It was observed that in day 5 embryos, PCBs resulted in a dose-dependent decrease of primordial germ cell (PGC) numbers, and caused PGCs pyknosis and vacuolation. Clomiphen failed to block the effects of PCBs. In the newly hatched chicken, PCBs induced a marked decrease in area of the transverse sections, diameter and relative area of the testicular tubules. The differentiation of germ cells was retarded after PCB treatment. In contrast, the area of the left ovarian transverse sections, the thickness of ovarian cortex and the number of oocytes increased dramatically in the female chickens after PCB exposure. In the adult chickens, PCBs caused no significant changes in body weight, respiration, heart rate, body temperature, red and white blood cell number, but induced a marked decrease in the testicular weight, and severe damage of the seminiferous tubules. The number of the spermatogenic cells and serum testosterone level were decreased significantly by PCBs. On the contrary, in the laying hens there was no significant effect of PCB on egg quality except a slight decrease in egg weight. These results indicated that PCBs exerted its disrupting effects on chicken reproduction with a sex and stage-related pattern, and in vivo disruption of gonadal development represents a possible model for risk assessment of environmental endocrine disrupters by in ovo treatment.

Administration, Oral↗