Rafael Jiménez

Rafael Jiménez
University of Granada | UGR · Department of Genetics

About

126
Publications
15,757
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1,911
Citations
Citations since 2017
24 Research Items
597 Citations
2017201820192020202120222023020406080100120
2017201820192020202120222023020406080100120
2017201820192020202120222023020406080100120
2017201820192020202120222023020406080100120

Publications

Publications (126)
Article
Full-text available
Background: Severe spermatogenic failure (SPGF) represents one of the most relevant causes of male infertility. This pathological condition can lead to extreme abnormalities in the seminal sperm count, such as severe oligozoospermia (SO) or non-obstructive azoospermia (NOA). Most cases of SPGF have an unknown aetiology, and it is known that this id...
Article
Full-text available
We conducted a genome-wide association study in a large population of infertile men due to unexplained spermatogenic failure (SPGF). More than seven million genetic variants were analysed in 1,274 SPGF cases and 1,951 unaffected controls from two independent European cohorts. Two genomic regions were associated with the most severe histological pat...
Article
Talpid moles and spotted hyenas have become the paradigms of anatomical and behavioral female masculinization. Females of many mole species develop ovotestes that produce testosterone, show external genitalia that resemble that of males, and close their vaginal orifice after every estrus, and female spotted hyenas lack an external vaginal orifice a...
Article
Full-text available
We aimed to analyze the role of the common genetic variants located in the PIN1 locus, a relevant prolyl isomerase required to control the proliferation of spermatogonial stem cells and the integrity of the blood–testis barrier, in the genetic risk of developing male infertility due to a severe spermatogenic failure (SPGF). Genotyping was performed...
Article
Full-text available
Background: Previous studies in animal models evidenced that genetic mutations of KATNAL1, resulting in dysfunction of its encoded protein, lead to male infertility through disruption of microtubule remodelling and premature germ cell exfoliation. Subsequent studies in humans also suggested a possible role of KATNAL1 single-nucleotide polymorphism...
Article
Full-text available
In species with seasonal breeding, male specimens undergo substantial testicular regression during the nonbreeding period of the year. However, the molecular mechanisms that control this biological process are largely unknown. Here, we report a transcriptomic analysis on the Iberian mole, Talpa occidentalis, in which the desquamation of live, nonap...
Article
The nail organ is a specialized appendage in which several ectodermal tissues coordinately function to sustain nail growth, a process that is coupled to digit regeneration. Here we show that the transcription factor Sox9 is expressed in several cell populations in the mouse digit tip. We found a SOX9⁺ cell population in the nail bed and genetic lin...
Preprint
Full-text available
In species with seasonal breeding, male specimens undergo substantial testicular regression during the non-breeding period of the year. However, the molecular mechanisms that control this biological process are largely unknown. Here, we report a transcriptomic analysis on the Iberian mole, Talpa occidentalis , in which the desquamation of live, non...
Article
Full-text available
Non-coding RNAs (ncRNAs) are a group of RNAs that do not encode functional proteins, including long non-coding RNAs (lncRNAs), microRNAs (miRNAs), PIWI-interacting RNAs (piRNAs), and short interfering RNAs (siRNAs). In the last 2 decades an effort has been made to uncover the role of ncRNAs during development and disease, and nowadays it is clear t...
Article
Full-text available
The crucial event in mammalian sexual differentiation occurs at the embryonic stage of sex determination, when the bipotential gonads differentiate as either testes or ovaries, according to the sex chromosome constitution of the embryo, XY or XX, respectively. Once differentiated, testes produce sexual hormones that induce the subsequent differenti...
Article
Full-text available
The frameshift hypothesis is a widely accepted model of bird wing evolution. This hypothesis postulates a shift in positional values, or molecular-developmental identity, that caused a change in digit phenotype. The hypothesis synthesized developmental and paleontological data on wing digit homology. The “most anterior digit” (MAD) hypothesis prese...
Article
Full-text available
Most mammalian species of the temperate zones of the Earth reproduce seasonally, existing a non-breeding period in which the gonads of both sexes undergo functional regression. It is widely accepted that photoperiod is the principal environmental cue controlling these seasonal changes, although several exceptions have been described in other mammal...
Article
Background Severe spermatogenic failure (SpF) represents the most extreme manifestation of male infertility, as it decreases drastically the semen quality leading to either severe oligospermia (SO, < 5 million spermatozoa/mL semen) or non‐obstructive azoospermia (NOA, complete lack of sperm in the ejaculate without obstructive causes). Objectives...
Article
Full-text available
In most mammals with seasonal reproduction, males undergo testis regression during the non-breeding period. We performed a morphological, hormonal, functional, and molecular study of the testes of sexually inactive males of two species of murine rodents, the wood mouse, Apodemus sylvaticus, and the Algerian mouse, Mus spretus, in syntopic populatio...
Article
Full-text available
Infertility is a growing concern in developed societies. Two extreme phenotypes of male infertility are non-obstructive azoospermia (NOA) and severe oligospermia (SO), which are characterized by severe spermatogenic failure (SpF). We designed a genetic association study comprising 725 Iberian infertile men as a consequence of SpF and 1058 unaffecte...
Article
Linking genomic variation to phenotypical traits remains a major challenge in evolutionary genetics. In this study, we use phylogenomic strategies to investigate a distinctive trait among mammals: the development of masculinizing ovotestes in female moles. By combining a chromosome-scale genome assembly of the Iberian mole, Talpa occidentalis, with...
Article
Intersexuality in female moles Female moles are intersexual and develop masculinizing ovotestes, a distinctive trait among mammals. Real et al. investigated the origin of this trait by sequencing the Iberian mole genome and applying comparative strategies that integrate transcriptomic, epigenetic, and chromatin interaction data. They identified mol...
Article
Full-text available
Objective To evaluate whether SOHLH2 intronic variation contributes to the genetic predisposition to male infertility traits, including severe oligospermia (SO) and different nonobstructive azoospermia (NOA) clinical phenotypes. Design Genetic association study. Setting Not applicable. Patient(s) Five hundred five cases (455 infertile patients d...
Article
The identification of new genes involved in sexual development and gonadal function as potential candidates causing male infertility is important for both diagnostic and therapeutic purposes. Deficiency of the onco-miRNA cluster miR-17∼92 has been shown to disrupt spermatogenesis, whereas mutations in its paralog cluster, miR-106b∼25, that is expre...
Article
Full-text available
Testes of seasonally breeding species experience a severe functional regression before the non-breeding period, which implies a substantial mass reduction due to massive germ-cell depletion. Two alternative mechanisms of seasonal germ-cell depletion have been described in mammals, apoptosis and desquamation (sloughing), but their prevalence has not...
Article
Full-text available
MicroRNAs are frequently organized into polycistronic clusters whose transcription is controlled by a single promoter. The miR-17-92 cluster is expressed in most embryonic and postnatal organs. It is a potent oncogene associated to several types of cancer and it is involved in several important developmental processes. In the testis, expression of...
Data
Bioinformatic analysis of the transcriptomes of control and SC-miR-17-92 KO testes. (XLS)
Data
Expression of PCNA and DMC1 in control and SC-miR-17-92 KO testes at P365. No difference between mutant (d-f) and control (a-c) testes was observed in the expression pattern of PCNA (a,d) and DMC1 (b,e) at P365. Scale bar shown in f represents 100 μm for all pictures. (TIF)
Article
Fossorial talpid moles use their limbs predominantly for digging, which explains their highly specialized anatomy. The humerus is particularly short and dorsoventrally rotated, with broadened distal and proximal parts where muscles attach and which facilitate powerful abductive movements. The radius and ulna are exceptionally robust and short. The...
Data
Comparison of the number of SOX9+ cells per testis tubule in both SC-DKO mutants and TX-treated controls (Sox9f/f;Sox8-/-).DOI: http://dx.doi.org/10.7554/eLife.15635.004
Data
List of 8910 genes showing significant differential expression respect to normal testis in both Dmrt1 and Sox9/8 mutants.DOI: http://dx.doi.org/10.7554/eLife.15635.022
Data
Comparison of the number of FOXL2+ cells per transversal testis cord section in Sox9/8 DKO (Sox9) WIN 18,446-treated mice and vehicle-injected controlsDOI: http://dx.doi.org/10.7554/eLife.15635.024
Data
Complete lists of genes included in the 8 molecular pathways mentioned in Figure 2—figure supplement 2. DOI: http://dx.doi.org/10.7554/eLife.15635.031
Data
Genes with significant differential expression among untreated controls, TX-treated controls, Sox8/9 SC-DKO mutants and control ovary at P150 (90 datx) identified from the bioinformatic analysis of our transcriptome.DOI: http://dx.doi.org/10.7554/eLife.15635.013
Data
Log2 fold change of expression of both Dmrt1 and Sox9/8 mutants respect to controls in a set of genes belonging to the all-trans-retinoic acid-mediated apoptosis path and RA receptors-mediated signaling from the PathCards database.DOI: http://dx.doi.org/10.7554/eLife.15635.023
Data
Comparison of the number of TUNEL-positive cells per section area unit in both SC-DKO mutants and TX-treated controls.DOI: http://dx.doi.org/10.7554/eLife.15635.026
Article
Full-text available
The new concept of mammalian sex maintenance establishes that particular key genes must remain active in the differentiated gonads to avoid genetic sex reprogramming, as described in adult ovaries after Foxl2 ablation. Dmrt1 plays a similar role in postnatal testes, but the mechanism of adult testis maintenance remains mostly unknown. Sox9 and Sox8...
Article
Males of all seasonal breeding mammals undergo circannual periods of testis involution resulting in almost complete ablation of the germinative epithelium. We performed a morphometric, histological, hormonal, and gene-expression study of the testes from winter and summer males of the greater white-toothed shrew, Crocidura russula, in populations of...
Article
Full-text available
G- and C-band pattern and NOR's of Talpa occidentalis metaphase chromosomes are described. The C-band pattern shows that the chromosomal pair causing karyotypic differences in the genus Talpa presents their short arm totally heterochromatic. The implication of this fact in the karyotypic evolution of this genus and the taxonomic status of T. occide...
Article
Full-text available
The C- and G-band patterns of Microtus nivalis metaphase chromosomes are described. The C-band pattern shows only centromeric C-bands in every autosome and reveals that the Y-chromosome is a medium sized element. No hetero- chromatic blocks were observed. All autosome pairs can be identified by its characteristic G-band pattern. This results are di...
Article
Males of all seasonal breeding mammals undergo circannual periods of testis involution resulting in almost complete ablation of the germinative epithelium. We performed a morphometric, histological, hormonal, and gene-expression study of the testes from winter and summer males of the greater white-toothed shrew, Crocidura russula, in populations of...
Article
In mammals, sex differentiation depends on gonad development, which is controlled by two groups of sex-determining genes that promote one gonadal sex and antagonize the opposite one. SOX9 plays a key role during testis development in all studied vertebrates, whereas it is kept inactive in the XX gonad at the critical time of sex determination, othe...
Article
Humans can unintentionally induce both positive and negative effects on wildlife presence and abundance, with organisms living in or associated with agricultural areas being good examples. Our study focused on a 1500 ha area (75 sampled 100 m × 50 m plots) at the driest edge of the endemic Iberian mole Talpa occidentalis distribution range, where t...
Article
Full-text available
In males of seasonally breeding species, testes undergo a severe involution at the end of the breeding season, with a major volume decrease due to massive germ-cell depletion associated with photoperiod-dependent reduced levels of testosterone and gonadotropins. Although it has been repeatedly suggested that apoptosis is the principal effector of t...
Article
The humerus of fossorial moles has a highly derived anatomy, reflecting the ecological specialization of these animals for digging. It is short and broad, with enlarged muscle attachment sites and pronounced articulations compared to non-fossorial sister taxa and other mammals. Both condyles are rotated in opposite directions, resulting in a torsio...
Article
No abstract available.
Article
Full-text available
Mammals have an XX/XY sex chromosomal sex determination system in which males represent the heterogametic sex. The Y-linked gene, SRY, determines sex by inducing the undifferentiated, bipotential gonads to differentiate as testes, which produce androgens and promote in this way the development of a male phenotype. Thus, in mammals, sex determinatio...
Article
Since the 1980s, a renewed understanding of molecular development has afforded an unprecedented level of knowledge of the mechanisms by which phenotype in animals and plants has evolved. In this volume, top scientists in these fields provide perspectives on how molecular data in biology help to elucidate key questions in estimating paleontological...
Article
Full-text available
Talpid moles show many specializations in their adult skeleton linked to fossoriality, including enlarged hands when compared to the feet. Heterochrony in developmental mechanisms is hypothesized to account for morphological evolution in skeletal elements. The temporal and spatial distribution of SOX9 expression, which is an early marker of chondri...
Article
This study provides a contribution to the reconstruction of the eulipotyphlan placental morphotype and also may help resolving a long-standing conflict about the interhaemal barrier in moles. As detailed descriptions of talpid placentation, only available for Talpa europaea and Scalopus aquaticus, led to a controversial debate on the nature of inte...
Article
Full-text available
Gonads are the only organs with 2 possible developmental pathways, testis or ovary. A consequence of this unique feature is that mutations in genes controlling gonad development give rise not only to gonadal malformation or dysfunction but also to frequent cases of sex reversal, including XY females, XX males and intersexes. Most of our current kno...
Article
According to the classical paradigm, the vasculature of the embryonic testis is more dense and complex than that of the ovary, but recent studies based on whole-mount detection of Caveolin-1 (CAV1) as an endothelial cell marker, have suggested that the level of ovarian vascularization is higher than previously assumed. However, this new hypothesis...
Article
Full-text available
In the adult testis, Sertoli cells (SCs) are the epithelial supporting cells of the seminiferous tubules that provide germ cells (GCs) with the required nutrients and structural and regulatory support to complete spermatogenesis. SCs also form the blood-testis barrier, phagocytose apoptotic spermatocytes and cell debris derived from spermiogenesis,...
Article
Full-text available
Talpid moles across all northern continents exhibit a remarkably large, sickle-like radial sesamoid bone anterior to their five digits, always coupled with a smaller tibial sesamoid bone. A possible developmental mechanism behind this phenomenon was revealed using molecular markers during limb development in the Iberian mole (Talpa occidentalis) an...
Article
Full-text available
Most testicular features undergo major circannual variation in seasonal breeding species. Although the ultimate cause of these variations is known to be the photoperiod in most cases, very little is known about the genetic mechanisms by which these changes are modulated in the testis. Many genes involved in testis development are known to be expres...
Article
In somatic cells of the rodent Eliomys quercinus (dormouse) nucleoli are found on chromosomes 14 and 22. Variation in silver stainability of nucleolar organizing regions at metaphase was concluded to reflect variation in nucleolar activity in the preceding interphase. It could be demonstrated that variation in nucleolar organizing region stainabili...
Article
Full-text available
Corneal development and structure were studied in the Iberian mole Talpa occidentalis, which has permanently closed eyelids, and the European mole Talpa europaea, in which the eyes are open. The vertebrate cornea typically maintains a three-layered structure - a stratified epithelium with protective and sensory function, an avascular, hypocellular,...
Article
Full-text available
Apoptosis and cell proliferation are two important cellular processes known to be involved in the normal functioning of the testis in nonseasonally breeding mammals, but there is some controversy concerning their roles in the gonads of males from seasonally breeding species. We have studied the processes of apoptosis and cell proliferation in the t...
Article
Full-text available
Animals adapted to dark ecotopes may experience selective pressure for retinal reduction. No previous studies have explicitly addressed the molecular basis of retinal development in any fossorial mammal. We studied retinal development and function in the Iberian mole Talpa occidentalis, which was presumed to be blind because of its permanently clos...
Article
Mammalian sex determination is the genetic process that commits the undifferentiated bipotential gonads to develop as either testes or ovaries. The differentiation of SOX9-expressing Sertoli cells is assumed to be necessary to initiate testis development. Insectivorous moles of the genus Talpa represent a unique case of generalized true hermaphrodi...
Article
Full-text available
Some cellular events are crucial in testis organogenesis, including Sertoli and Leydig cell differentiation, mesonephric cell migration and testis cord formation. These processes are controlled by transcription factors, paracrine signalling and hormones. Using the mole species Talpa occidentalis as an alternative animal model, we report the express...
Article
The mammalian ovary shows extensive variation mainly in relation to the interstitial tissue of the ovary, the so-called interstitial gland, and the degree of gonad regionalisation, which implies the existence of a cortex and a medulla. Three mammalian species, mouse, human, and mole, have been reviewed here as representative animal models for ovari...
Article
Full-text available
Fossorial mammals face natural selection pressures that differ from those acting on surface dwelling animals, and these may lead to reduced visual system development. We have studied eye development in a species of true mole, the Iberian mole Talpa occidentalis, and present the molecular basis of abnormal lens development. This is the first embryol...
Article
Previous studies of the reproductive biology and genetics of European moles (Talpa spp.) showed that all females of these species have ovotestes (gonads with testicular and ovarian tissue) instead of normal ovaries, a unique specialization among mammals. Females are fertile as their ovarian tissue is fully functional. Testicular tissue is abnormal...
Article
Full-text available
In mammals, germ cells are important both during development and for the function of female gonads, whereas male gonads may develop in the absence of germ cells. The gonads of female moles (genus Talpa) develop according to a testis-like pattern which results in the formation of ovotestes. In this paper, we studied the expression pattern of several...
Article
The facultative heterochromatic X chromosome in leptotene spermatocytes of the grasshopper Eyprepocnemis plorans showed marked hypoacetylation for lysine 9 in the H3 histone (H3-K9) with no sign of histone H2AX phosphorylation. Since H3-K9 hypoacetylation precedes the meiotic appearance of phosphorylated H2AX (gamma-H2AX), which marks the beginning...
Article
Moles are unique among mammals because all females of several species of genus Talpa have bilateral ovotestes (gonads with both ovarian and testicular tissue). Based on the analysis of a large sample of embryos, foetuses and infants over a 13-year period, we have studied the development of the gonads in male and female moles of the species Talpa oc...
Article
Full-text available
Moles are the only fertile true hermaphrodites described up to now among mammals. This paper investigates the development and growth of the mole Talpa occidentalis. Fifteen developmental stages (8 prenatal and 7 postnatal) were established and 12 of them, ranging from early gestation to weaning, are described in detail. The growth of moles was show...
Article
Traditionally, B chromosomes have been classified as parasitic or heterotic, depending of whether or not they show selfish behaviour. Nevertheless, experimental evidence has been found supporting the idea that supernumerary chromosomes may evolve from parasitism to neutrality. In this work, B chromosome transmission in Rattus rattus has been analys...
Article
Full-text available
We have performed a morphological, hormonal and molecular study of the development of the sex ducts in the mole Talpa occidentalis. Females develop bilateral ovotestes with a functional ovarian portion and disgenic testicular tissue. The Müllerian ducts develop normally in females and their regression is very fast in males, suggesting a powerful ac...