Segregation Of Sex Chromosomes Research Articles

12333 46 XX/XY Chimerism - Positive NIPT And Post-natal Karyotype Is It Real?

Abstract Disclosure: K.L. Del Rosario: None. N. Sheriden: None. N. Vijayakanthi: None. Introduction: Non-Invasive Prenatal Testing(NIPT) using cell free fetal DNA in plasma of pregnant women has become a routine part of prenatal care in screening for fetal aneuploidies including sex chromosome abnormalities in most regions around the world. False positive results are increasingly imposing challenges in pre-natal as well as post-natal care. Case Discussion: We report a neonate born at 32+2 weeks gestation to a 42-year-old G2 P2 mother. Pregnancy was complicated by insulin dependent maternal type 2 diabetes mellitus, maternal chronic hypertension and a positive NIPT for high-risk monosomy X. Prenatal ultrasound showed male anatomy. Interestingly on physical exam after birth, the neonate had typical male external genitalia with bilateral normal male gonads. Chromosome analysis done immediately after birth revealed the presence of two cell lines: 40 of the 50 cells (80%) had a normal female 46 XX karyotype and 10 of the 50 cells (20%) had a normal male 46 XY karyotype. These findings could be due to reabsorbed twin, Klinefelter syndrome with two trisomy rescue events, maternal cell contamination or true chimerism. In addition, fluorescence in situ hybridization (FISH) analysis for X and Y probes revealed the presence of two cell lines. The first cell line (70% of the cells) had two hybridization signals for chromosome X and the second cell line (∼25% of the cells) had one hybridization signal for chromosome X and one for chromosome Y. Postnatal ultrasound showed normal testicles with no evidence of Mullerian structures. Newborn screening was negative for congenital adrenal hyperplasia (CAH). Genetics was consulted and recommended repeat chromosomal analysis, parental testing to determine sex chromosome segregation, and follow-up with pediatric endocrinology. Repeat cytogenetic testing at 2 weeks of life resulted in a normal male chromosome complement of 46,XY. Previous abnormal cytogenetics were thought to be due to maternal cell contamination. Further endocrine labs showed LH(1.16 uIU/ml) and testosterone levels ( 87 ng/dL), appropriate levels for age indicating normal Hypothalamic Pituitary Gonadal (HPG) axis and testicular Leydig cell function. Since the family was previously counseled regarding the concept of maternal cell contamination, they expressed understanding and were happy with the update of the normal karyotype result. Conclusion: False-positive results concerning for rare chimerism on NIPT can occur and should prompt a thorough history, physical exam, ultrasound studies and repeat testing to confirm its presence. Careful consideration should be taken when counseling family about the implications of these results, especially communication about gender assignment of the infant. Presentation: 6/3/2024

Evolutionary dynamics of pseudoautosomal region 1 in humans and great apes

BackgroundThe pseudoautosomal region 1 (PAR1) is a 2.7 Mb telomeric region of human sex chromosomes. PAR1 has a crucial role in ensuring proper segregation of sex chromosomes during male meiosis, exposing it to extreme recombination and mutation processes. We investigate PAR1 evolution using population genomic datasets of extant humans, eight populations of great apes, and two archaic human genome sequences.ResultsWe find that PAR1 is fast evolving and closer to evolutionary nucleotide equilibrium than autosomal telomeres. We detect a difference between substitution patterns and extant diversity in PAR1, mainly driven by the conflict between strong mutation and recombination-associated fixation bias at CpG sites. We detect excess C-to-G mutations in PAR1 of all great apes, specific to the mutagenic effect of male recombination. Despite recent evidence for Y chromosome introgression from humans into Neanderthals, we find that the Neanderthal PAR1 retained similarity to the Denisovan sequence. We find differences between substitution spectra of these archaics suggesting rapid evolution of PAR1 in recent hominin history. Frequency analysis of alleles segregating in females and males provided no evidence for recent sexual antagonism in this region. We study repeat content and double-strand break hotspot regions in PAR1 and find that they may play roles in ensuring the obligate X-Y recombination event during male meiosis.ConclusionsOur study provides an unprecedented quantification of population genetic forces governing PAR1 biology across extant and extinct hominids. PAR1 evolutionary dynamics are predominantly governed by recombination processes with a strong impact on mutation patterns across all species.

Histone H3 Methylation and Autosomal vs. Sex Chromosome Segregation During Male Meiosis in Heteroptera

Heteropteran insects exhibit a remarkable diversity of meiotic processes, including coexistence of different chromosomes types with different behavior during the first meiotic division, non-chiasmatic segregation, and inverted meiosis. Because of this diversity they represent suitable models to study fundamental questions about the mechanisms of chromosome behavior during cell division. All heteropteran species possess holokinetic chromosomes and in most of them the autosomal chromosomes synapse, recombine, and undergoe pre-reductional meiosis. In contrast, the sex chromosomes are achiasmatic, behave as univalents at metaphase I and present an inverted or post-reductional meiosis. An exception to this typical behavior is found in Pachylis argentinus, where both the autosomes and the X-chromosome divide reductionally at anaphase I and then divide equationally at anaphase II. In the present report, we analyzed the distribution of histones H3K9me2 and H3K9me3 in P. argentinus and in five species that have simple and multiple sex chromosome systems with typical chromosome segregation, Belostoma elegans, B. oxyurum, Holhymenia rubiginosa, Phthia picta, and Oncopeltus unifasciatellus. We found that H3K9me3 is a marker for sex-chromosomes from early prophase I to the end of the first division in all the species. H3K9me2 also marks the sex chromosomes since early prophase but shows different dynamics at metaphase I depending on the sex-chromosome segregation: it is lost in species with equationally dividing sex chromosomes but remains on one end of the X chromosome of P. argentinus, where chromatids migrate together at anaphase I. It is proposed that the loss of H3K9me2 from the sex chromosomes observed at metaphase I may be part of a set of epigenetic signals that lead to the reductional or equational division of autosomes and sex chromosomes observed in most Heteroptera. The present observations suggest that the histone modifications analyzed here evolved in Heteroptera as markers for asynaptic and achiasmatic sex chromosomes during meiosis to allow the distinction from the chiasmatic autosomal chromosomes.

Meiotic Behavior of Achiasmate Sex Chromosomes in the African Pygmy Mouse Mus mattheyi Offers New Insights into the Evolution of Sex Chromosome Pairing and Segregation in Mammals.

X and Y chromosomes in mammals are different in size and gene content due to an evolutionary process of differentiation and degeneration of the Y chromosome. Nevertheless, these chromosomes usually share a small region of homology, the pseudoautosomal region (PAR), which allows them to perform a partial synapsis and undergo reciprocal recombination during meiosis, which ensures their segregation. However, in some mammalian species the PAR has been lost, which challenges the pairing and segregation of sex chromosomes in meiosis. The African pygmy mouse Mus mattheyi shows completely differentiated sex chromosomes, representing an uncommon evolutionary situation among mouse species. We have performed a detailed analysis of the location of proteins involved in synaptonemal complex assembly (SYCP3), recombination (RPA, RAD51 and MLH1) and sex chromosome inactivation (γH2AX) in this species. We found that neither synapsis nor chiasmata are found between sex chromosomes and their pairing is notably delayed compared to autosomes. Interestingly, the Y chromosome only incorporates RPA and RAD51 in a reduced fraction of spermatocytes, indicating a particular DNA repair dynamic on this chromosome. The analysis of segregation revealed that sex chromosomes are associated until metaphase-I just by a chromatin contact. Unexpectedly, both sex chromosomes remain labelled with γH2AX during first meiotic division. This chromatin contact is probably enough to maintain sex chromosome association up to anaphase-I and, therefore, could be relevant to ensure their reductional segregation. The results presented suggest that the regulation of both DNA repair and epigenetic modifications in the sex chromosomes can have a great impact on the divergence of sex chromosomes and their proper transmission, widening our understanding on the relationship between meiosis and the evolution of sex chromosomes in mammals.

Flavors of Non-Random Meiotic Segregation of Autosomes and Sex Chromosomes

Segregation of chromosomes is a multistep process occurring both at mitosis and meiosis to ensure that daughter cells receive a complete set of genetic information. Critical components in the chromosome segregation include centromeres, kinetochores, components of sister chromatid and homologous chromosomes cohesion, microtubule organizing centres, and spindles. Based on the cytological work in the grasshopper Brachystola, it has been accepted for decades that segregation of homologs at meiosis is fundamentally random. This ensures that alleles on chromosomes have equal chance to be transmitted to progeny. At the same time mechanisms of meiotic drive and an increasing number of other examples of non-random segregation of autosomes and sex chromosomes provide insights into the underlying mechanisms of chromosome segregation but also question the textbook dogma of random chromosome segregation. Recent advances provide a better understanding of meiotic drive as a prominent force where cellular and chromosomal changes allow autosomes to bias their segregation. Less understood are mechanisms explaining observations that autosomal heteromorphism may cause biased segregation and regulate alternating segregation of multiple sex chromosome systems or translocation heterozygotes as an extreme case of non-random segregation. We speculate that molecular and cytological mechanisms of non-random segregation might be common in these cases and that there might be a continuous transition between random and non-random segregation which may play a role in the evolution of sexually antagonistic genes and sex chromosome evolution.

Occurrence of Hypopituitarism in Tunisian Turner Syndrome patients: familial versus sporadic cases

Objective To explore unusual association between Turner Syndrome (TS) and Hypopituitarism in a Tunisian cohort. Methods We reported 6 patients with TS associated to Hypopituitarism, including three familial cases except the fourth sister who showed only a TS phenotype. Biochemical analysis, resonance magnetic imaging and cytogenetic analyses were performed. Results The average age of our patients was 17.2 years (11–31 years). They were all referred for short stature and pubertal delay, except for the fourth sister who presented spontaneous puberty with the integrity of the pituitary axis and the presence of an X ring chromosome. Karyotype analysis showed monosomy in 3 cases and a mosaic TS in the 3 remaining cases, including one patient with abnormal X chromosome structure. Somatotropic and corticotropic deficiencies were confirmed in 2 sporadic cases while the gonadotropic and thyrotropic axes were spared. In contrast; familial cases were consistently affected by the integrity of the corticotropic axis. MRI showed pituitary hypoplasia in all familial cases and pituitary stalk interruption syndrome in only one sporadic case. No correlation was found between the chromosome formula and the anterior pituitary involvement. Conclusion Co-segregation of congenital Hypopituitarism with pituitary hypoplasia and X chromosome aberrations could imply a molecular anomaly of transcription factors responsible for the differentiation and development of pituitary cells such as PROP1, POUF1, Hesx1, Lhx3, Lhx4. The etiopathogenic link between X chromosome abnormalities and the occurrence of Hypopituitarism remains unclear; however, the progress of molecular biology may clarify the interrelation between transcription factors and sex chromosome segregation abnormalities.

Exogenous Progesterone for Offspring Sex Ratio Manipulation in Arabic Chickens (Gallus turcicus) Leading to Increasing Female Chicks Proportion

Female birds of egg-laying hens are more valuable than males, because males bird have no commercial value. The opportunity to manipulate offspring sex ratio in poultry has been observed in female birds; hence, female birds have heterogametic ZW chromosomes. High progesterone concentration 2-5 h before ovulation is thought to affect the segregation of female sex chromosomes as the basis for determining the sex of offspring. This study aimed to investigate the effect of progesterone induction in Arabic hens, which was conducted 5 h before ovulation, along with the time of the first meiosis; therefore, segregation of sex chromosomes leading to an increase in female offspring. The study utilized on 60 Arabic hens divided into three treatment groups: Without injection (P0), progesterone injection 1 mg/hen, (P1), progesterone injection 2 mg/hen (P2). The results showed that the percentage of female offspring at P0 and P1 was 54.74 and 53.33%, respectively, while P2 hens resulted in 62.92% females, the highest female offspring rate than the other groups. Chi-square analysis of sex ratio showed that P0 and P1 hens had no significant effect (P>0.05) while P2 hens being significant (P<0.05) from the expected sex ratio (50:50). Progesterone concentration of hens produced female offspring in the P2 group was 7.15 ng/ml being highly significant (P<0.05) than that found in the hens produced male offspring (4.53 ng/ml). Progesterone 5 h preceding ovulation in the Arabic hens with a 2 mg/hen dose can increase the proportion of female offspring; therefore, an opportunity for sex ratio manipulation in Arabic chickens.

Corticosterone and testosterone treatment influence expression of gene pathways linked to meiotic segregation in preovulatory follicles of the domestic hen.

Decades of work indicate that female birds can control their offspring sex ratios in response to environmental and social cues. In laying hens, hormones administered immediately prior to sex chromosome segregation can exert sex ratio skews, indicating that these hormones may act directly on the germinal disc to influence which sex chromosome is retained in the oocyte and which is discarded into an unfertilizable polar body. We aimed to uncover the gene pathways involved in this process by testing whether treatments with testosterone or corticosterone that were previously shown to influence sex ratios elicit changes in the expression of genes and/or gene pathways involved in the process of meiotic segregation. We injected laying hens with testosterone, corticosterone, or control oil 5h prior to ovulation and collected germinal discs from the F1 preovulatory follicle in each hen 1.5h after injection. We used RNA-sequencing (RNA-seq) followed by DESeq2 and gene set enrichment analyses to identify genes and gene pathways that were differentially expressed between germinal discs of control and hormone-treated hens. Corticosterone treatment triggered downregulation of 13 individual genes, as well as enrichment of gene sets related to meiotic spindle organization and chromosome segregation, and additional gene sets that function in ion transport. Testosterone treatment triggered upregulation of one gene, and enrichment of one gene set that functions in nuclear chromosome segregation. This work indicates that corticosterone can be a potent regulator of meiotic processes and provides potential gene targets on which corticosterone and/or testosterone may act to influence offspring sex ratios in birds.

Y/15 and Y/22 Derivative Chromosomes in Couples with Reproductive Failures: Algorithm of Preimplantation Genetic Testing and Specificity of Inheritance

The present study reports on the results of preimplantation genetic testing and IVF outcomes in four families, where one of the spouses is a carrier of Y/15 or Y/22 derivative chromosome: three cases of male carriers and one—of female carrier. In the cases of male carriers, we detected the predominant inheritance of the derivative chromosomes by the embryos and no abnormalities in sex chromosome segregation. In the case of female carrier, we did not observe either predominant inheritance of derivative chromosome by the embryos or effect of derivative chromosome on sex chromosome segregation. In all families, we revealed a high frequency of embryonic aneuploidies of chromosomes other than those involved in translocation. To exclude inheritance of the derivative chromosome by the offspring, preimplantation genetic testing should be recommended: fluorescent in situ hybridization (FISH), which allows identification of the Y-chromosome satellite DNA, followed by next generation sequencing (NGS) or microarray comparative genomic hybridization (aCGH) to detect other genomic and chromosomal abnormalities.

Sex expression and genotypic sex ratio vary with region and environment in the wetland moss Drepanocladus lycopodioides

Abstract Sex ratio variation is common among organisms with separate sexes. In bryophytes, sex chromosome segregation at meiosis suggests a balanced progeny sex ratio. However, most bryophyte populations exhibit female-biased phenotypic sex ratios based on the presence of reproductive structures on gametophytes. Many bryophyte populations do not form sexual organs, and genotypic sex ratio variation in such populations is mostly unknown. We tested sex expression, and phenotypic and genotypic sex ratios against environmental parameters in natural populations of the unisexual wetland moss Drepanocladus lycopodiodes at 11 sites in each of three regions in southern Sweden. We identified sex in 660 individual ramets, based on sexual structures, when present, or with a specifically designed molecular marker, when absent. All regions exhibited a female bias in phenotypic and genotypic sex ratios. Sex ratio biases and sex expression differed between regions. Sex ratios were less female-biased in larger patches. Wetter patches exhibited a stronger female bias in genotypic sex ratio and lower sex expression. This is the first evidence of environmental effects on genotypic sex ratio in mosses. A higher frequency of females in wet patches could be due to higher female resource demands for sporophyte production or higher male sensitivity to wetness. A higher incidence of females than males in moister sites aligns with female flowering plants, but differs from reproductive bryophytes in drier environments. Taken together with previous results, our data indicate that sex ratio variation and its drivers differ among species, their life histories and environments.

Drivers of sex ratio bias in the eastern bongo: lower inbreeding increases the probability of being born male.

Parent sex ratio allocation has consequences for individual fitness, population dynamics, and conservation. Theory predicts that parents should adjust offspring sex ratio when the fitness returns of producing male or female offspring varies. Previous studies have assumed that only mothers are capable of biasing offspring sex ratios, but have neglected fathers, given the expectation of an equal proportion of X- and Y-chromosome-bearing (CBS) sperm in ejaculates due to sex chromosome segregation at meiosis. This assumption has been recently refuted and both paternal fertility and paternal genetic quality have been shown to bias sex ratios. Here, we simultaneously test the relative contribution of paternal, maternal, and individual genetic quality, as measured by inbreeding, on the probability of being born a son or a daughter, using pedigree and lifelong offspring sex ratio data for the eastern bongo ( Tragelaphus eurycerus isaaci). Our models showed first, that surprisingly, as individual inbreeding decreases the probability of being born male increases, second, that paternal genetic effects on sex ratio were stronger than maternal genetic effects (which were absent). Furthermore, paternal effects were opposite in sign to those predicted; father inbreeding increases the probability of having sons. Previous paternal effects have been interpreted as adaptive due to sex-specific inbreeding depression for reproductive traits. We argue that in the eastern bongo, the opposite sign of the paternal effect on sex ratios results from a reversed sex-specific inbreeding depression pattern (present for female but not male reproductive traits). We anticipate that this research will help stimulate research on evolutionary constraints to sex ratios. Finally, the results open a new avenue of research to predict sex ratio allocation in an applied conservation context. Future models of sex ratio allocation should also include the predicted inbreeding level of the offspring and paternal inbreeding levels.

RNAi Doxxes Segregation Distorters on the X

Species with chromosomal sex determination are susceptible to an evolutionary tug-of-war over sex chromosome segregation. RNA silencing has been proposed to play a role in this intragenomic conflict. Reporting in Developmental Cell, Lin etal. (2018) demonstrate that RNA interference is key to this conflict as a genome defender.

Relationship Between Sequence Homology, Genome Architecture, and Meiotic Behavior of the Sex Chromosomes in North American Voles.

In most mammals, the X and Y chromosomes synapse and recombine along a conserved region of homology known as the pseudoautosomal region (PAR). These homology-driven interactions are required for meiotic progression and are essential for male fertility. Although the PAR fulfills key meiotic functions in most mammals, several exceptional species lack PAR-mediated sex chromosome associations at meiosis. Here, we leveraged the natural variation in meiotic sex chromosome programs present in North American voles (Microtus) to investigate the relationship between meiotic sex chromosome dynamics and X/Y sequence homology. To this end, we developed a novel, reference-blind computational method to analyze sparse sequencing data from flow-sorted X and Y chromosomes isolated from vole species with sex chromosomes that always (Microtus montanus), never (Microtus mogollonensis), and occasionally synapse (Microtus ochrogaster) at meiosis. Unexpectedly, we find more shared X/Y homology in the two vole species with no and sporadic X/Y synapsis compared to the species with obligate synapsis. Sex chromosome homology in the asynaptic and occasionally synaptic species is interspersed along chromosomes and largely restricted to low-complexity sequences, including a striking enrichment for the telomeric repeat sequence, TTAGGG. In contrast, homology is concentrated in high complexity, and presumably euchromatic, sequence on the X and Y chromosomes of the synaptic vole species, M. montanus Taken together, our findings suggest key conditions required to sustain the standard program of X/Y synapsis at meiosis and reveal an intriguing connection between heterochromatic repeat architecture and noncanonical, asynaptic mechanisms of sex chromosome segregation in voles.

Cytogenetic analysis of five Ctenidae species (Araneae): detection of heterochromatin and 18S rDNA sites.

The present study aimed to cytogenetically analyse five Ctenidae species Ctenus ornatus (Keyserling, 1877), Ctenus medius (Keyserling, 1891), Phoneutria nigriventer (Keyserling, 1891), Viracucha andicola (Simon, 1906), and Enoploctenus cyclothorax (Philip Bertkau, 1880), from Brazil. All species presented a 2n♂ = 28 except for V. andicola, which showed 2n♂ = 29. Analysis of segregation and behavior of sex chromosomes during male meiosis showed a sex chromosome system of the type X1X20 in species with 28 chromosomes and X1X2X30 in V. andicola. C banding stained with fluorochromes CMA3 and DAPI revealed two distributions patterns of GC-rich heterochromatin: (i) in terminal regions of most chromosomes, as presented in C. medius, P. nigriventer, E. cyclothorax and V. andicola and (ii) in interstitial regions of most chromosomes, in addition to terminal regions, as observed for C. ornatus. The population of Ubatuba (São Paulo State) of this same species displayed an additional accumulation of GC-rich heterochromatin in one bivalent. Fluorescent in situ hybridization revealed that this bivalent corresponded to the NOR-bearing chromosome pair. All analyzed species have one bivalent with 18S rDNA site, except P. nigriventer, which has three bivalents with 18S rDNA site. Karyotypes of two species, C. medius and E. cyclothorax, are described for the first time. The latter species is the first karyotyped representative of the subfamily Acantheinae. Finally, 18S rDNA probe is used for the first time in Ctenidae at the present study.

A father effect explains sex-ratio bias.

Sex ratio allocation has important fitness consequences, and theory predicts that parents should adjust offspring sex ratio in cases where the fitness returns of producing male and female offspring vary. The ability of fathers to bias offspring sex ratios has traditionally been dismissed given the expectation of an equal proportion of X- and Y-chromosome-bearing sperm (CBS) in ejaculates due to segregation of sex chromosomes at meiosis. This expectation has been recently refuted. Here we used Peromyscus leucopus to demonstrate that sex ratio is explained by an exclusive effect of the father, and suggest a likely mechanism by which male-driven sex-ratio bias is attained. We identified a male sperm morphological marker that is associated with the mechanism leading to sex ratio bias; differences among males in the sperm nucleus area (a proxy for the sex chromosome that the sperm contains) explain 22% variation in litter sex ratio. We further show the role played by the sperm nucleus area as a mediator in the relationship between individual genetic variation and sex-ratio bias. Fathers with high levels of genetic variation had ejaculates with a higher proportion of sperm with small nuclei area. This, in turn, led to siring a higher proportion of sons (25% increase in sons per 0.1 decrease in the inbreeding coefficient). Our results reveal a plausible mechanism underlying unexplored male-driven sex-ratio biases. We also discuss why this pattern of paternal bias can be adaptive. This research puts to rest the idea that father contribution to sex ratio variation should be disregarded in vertebrates, and will stimulate research on evolutionary constraints to sex ratios-for example, whether fathers and mothers have divergent, coinciding, or neutral sex allocation interests. Finally, these results offer a potential explanation for those intriguing cases in which there are sex ratio biases, such as in humans.

Differential cohesin loading marks paired and unpaired regions of platypus sex chromosomes at prophase I

Cohesins are vital for chromosome organisation during meiosis and mitosis. In addition to the important function in sister chromatid cohesion, these complexes play key roles in meiotic recombination, DSB repair, homologous chromosome pairing and segregation. Egg-laying mammals (monotremes) feature an unusually complex sex chromosome system, which raises fundamental questions about organisation and segregation during meiosis. We discovered a dynamic and differential accumulation of cohesins on sex chromosomes during platypus prophase I and specific reorganisation of the sex chromosome complex around a large nucleolar body. Detailed analysis revealed a differential loading of SMC3 on the chromatin and chromosomal axis of XY shared regions compared with the chromatin and chromosomal axes of asynapsed X and Y regions during prophase I. At late prophase I, SMC3 accumulation is lost from both the chromatin and chromosome axes of the asynaptic regions of the chain and resolves into subnuclear compartments. This is the first report detailing unpaired DNA specific SMC3 accumulation during meiosis in any species and allows speculation on roles for cohesin in monotreme sex chromosome organisation and segregation.

Dosage Compensation in Drosophila-a Model for the Coordinate Regulation of Transcription.

The sex chromosomes have special significance in the history of genetics. The chromosomal basis of inheritance was firmly established when Calvin Bridges demonstrated that exceptions to Mendel's laws of segregation were accompanied at the cytological level by exceptional sex chromosome segregation. The morphological differences between X and Y exploited in Bridges' experiments arose as a consequence of the evolution of the sex chromosomes. Originally a homologous chromosome pair, the degeneration of the Y chromosome has been accompanied by a requirement for increased expression of the single X chromosome in males. Drosophila has been a model for the study of this dosage compensation and has brought key strengths, including classical genetics, the exceptional cytology of polytene chromosomes, and more recently, comprehensive genomics. The impact of these studies goes beyond sex chromosome regulation, providing valuable insights into mechanisms for the establishment and maintenance of chromatin domains, and for the coordinate regulation of transcription.

Endogenous Corticosterone Elevations Five Hours Prior to Ovulation do not Influence Offspring Sex Ratios in Zebra Finches

Previous research suggests that environmental and social factors can drive female birds to bias offspring sex ratios. The underlying mechanisms controlling these adjustments remain unclear. Results from experimental and correlative research suggest that maternal corticosterone plays an important role in this process. Since females are the heterogametic sex in birds, corticosterone may potentially bias offspring sex ratios during meiotic segregation, through non-random segregation of sex chromosomes. In a previous study, we showed that pharmacological elevations of corticosterone near the time of meiotic segregation exerted an effect on offspring sex ratio, causing female Zebra Finches ( Taeniopygia guttata) to produce significantly more males. Here, we aimed to determine whether endogenous elevations in the physiological range have similar effects on offspring sex. First we examined offspring sex ratio in relation to baseline corticosterone levels to determine if natural variation in circulating corticosterone near the time of meiotic segregation is related to offspring sex ratio. Next, we used a 5-minute bag handling protocol to induce corticosterone elevations 5 hours prior to ovulation. Maternal baseline corticosterone levels did not correlate with average clutch sex ratios. In addition, the sex ratios produced by females exposed to handling stress did not differ from sex ratios produced by unmanipulated females. Together these results suggest that physiological levels of endogenous corticosterone, both baseline and acutely elevated near the time of sex determination may not be involved in the adjustment of primary sex ratios in Zebra Finches.

Back to the roots: segregation of univalent sex chromosomes in meiosis.

In males of many taxa, univalent sex chromosomes normally segregate during the first meiotic division, and analysis of sex chromosome segregation was foundational for the chromosome theory of inheritance. Correct segregation of single or multiple univalent sex chromosomes occurs in a cellular environment where every other chromosome is a bivalent that is being partitioned into homologous chromosomes at anaphase I. The mechanics of univalent chromosome segregation vary among animal taxa. In some, univalents establish syntelic attachment of sister kinetochores to the spindle. In others, amphitelic attachment is established. Here, we review how this problem of segregation of unpaired chromosomes is solved in different animal systems. In addition, we give a short outlook of how mechanistic insights into this process could be gained by explicitly studying model organisms, such as Caenorhabditis elegans.

Sex chromosome recombination failure, apoptosis, and fertility in male mice.

Lack of crossing-over in meiosis can trigger an apoptotic response at metaphase I by the spindle assembly checkpoint (SAC). In contrast to females, segregation of sex chromosomes in males poses a particular challenge as recombination and chiasma formation is restricted to the pseudoautosomal region, the small region of homology between X and Y chromosomes. Existing data indicate that low levels of crossover failure in male meiosis can be tolerated without compromising fertility, while high levels of X-Y dissociation (in ≥70% of cells) result in widespread apoptosis and subsequent infertility, demonstrated earlier, e.g., in Spo11β-only mice. Here, we explore the threshold of X-Y recombination failure frequency that is compatible with fertility. We show that in Spo11β-only(mb) mice with a mixed genetic background, in contrast to Spo11β-only mice with a C57BL/6 background, X-Y pairing fails in ~50% of cells but this still allows for sperm production without any overt impact on fertility. We also review data on apoptosis and fertility from other achiasmate mouse models and propose that the incidence of homolog dissociation that can be tolerated in vivo without compromising male fertility lies between 50 and 70%.