Hundreds of thousands of copies of DNA sequences have been incorporated into the genomes of higher organisms.

/pdf/repeated-sequences-in-dna-4tcffmb3h2.pdf

Repeated Sequences in DNA

https://www.cell.com/cell/pdf/S0092-8674(05)80085-6.pdf

Role of Insulin-like Growth Factors in Embryonic and Postnatal Growth

The initiation of male development in mammals requires one or more genes on the Y chromosome. A recently isolated gene, termed SRY in humans and Sry in mouse, has many of the genetic and biological properties expected of a Y-located testis-determining gene. It is now shown that Sry on a 14-kilobase genomic DNA fragment is sufficient to induce testis differentiation and subsequent male development when introduced into chromosomally female mouse embryos.

Male development of chromosomally female mice transgenic for Sry

A gene mapping to the sex-determining region of the mouse Y chromosome is deleted in a line of XY female mice mutant for Tdy, and is expressed at a stage during male gonadal development consistent with its having a role in testis determination. This gene is a member of a new family of at least five mouse genes, related by an amino-acid motif showing homology to other known or putative DNA-binding domains.

A gene mapping to the sex-determining region of the mouse Y chromosome is a member of a novel family of embryonically expressed genes

Sources, Effects and Risks of Ionizing Radiation

During embryogenesis, primordial germ cells (PGCs) have the potential to enter either spermatogenesis or oogenesis. In a female genital ridge, or in a non-gonadal environment, PGCs develop as meiotic oocytes. However, male gonadal somatic cells inhibit PGCs from entering meiosis and direct them to a spermatogenic fate. We have examined the ability of PGCs from male and female embryos to respond to the masculinising environment of the male genital ridge, defining a temporal window during which PGCs retain a bipotential fate. To help understand how PGCs respond to the male gonadal environment, we have identified molecular differences between male PGCs that are committed to spermatogenesis and bipotential female PGCs. Our results suggest that one way in which PGCs respond to this masculinising environment is to synthesise prostaglandin D 2 . We show that this signalling molecule can partially masculinise female embryonic gonads in culture, probably by inducing female supporting cells to differentiate into Sertoli cells. In the developing testis, prostaglandin D 2 may act as a paracrine factor to induce Sertoli cell differentiation. Thus part of the response of PGCs to the male gonadal environment is to generate a masculinising feedback loop to ensure male differentiation of the surrounding gonadal somatic cells.

Sexually dimorphic development of mouse primordial germ cells: switching from oogenesis to spermatogenesis.

1. The origin and potential uses of the method of egg transfer in mammals are briefly surveyed. 2. An experiment is described in which genetically labelled fertilized mouse eggs were transferred to the left uterine horns of recipient female mice. Eggs were obtained both by induced ovulation of sexually immature donors and by spontaneous ovulation of adult donors. Both pregnant and pseudo-pregnant recipients were used. The post-coital stages of donors and recipients were independently varied. At 16½ or 17½ days post-coitum the recipients were killed and their uterine contents recorded. 3. The operation had no effect upon the recipients9 chances of becoming pregnant, nor did it have substantial effects upon the implantation and subsequent survival of eggs in the uninjected horn of the uterus. 4. In the injected horn, the implantation rate was reduced by about one-third in recipients both at 2½ and 3½ days post-coitum. Post-implantational mortality in the injected horn was increased in 3½-day recipients, but not in 2½-day recipients, except when the operation was accompanied by gross surgical trauma. 5. The yield of live embryos from eggs transferred to recipients which had themselves been mated to fertile males was highest in the 3½ → 2½ days combination, lowest in the 2½ → 3½ days combination, and intermediate in the two synchronous combinations. These differences may in part be attributable to competition between native and transferred eggs. Such competition was shown mainly to occur before,during or shortly after implantation, and to be a property of non-synchronous rather than synchronous donor-recipient combinations. But the differences were in part independent of the presence of competing native eggs, as shown by transfers to recipients mated to sterile males; the yield from the 3½ → 2½ combination was still very much greater than that obtained from the 2½ → 3½ combination. 6: Transfers of eggs artificially ovulated from sexually immature donors gave results in all respects similar to those obtained with eggs spontaneously ovulated by sexually mature donors. 7. The distribution of alien embryos among the recipients suggested that apart from the random loss of parts of inocula through escape or death of individual eggs, there was another and distinct process at work causing the loss of whole inocula as units. 8. Over the range tested (0-18 eggs) the number of alien embryos and the number of implantations of all sorts in the injected horn rose linearly with increasing numbers of eggs injected. The number of native embryos in the injected horn declined with increasing numbers of eggs injected. 9. When the number of implantations, with increasing numbers of eggs injected, began to exceed the normal quota for one horn, the number of live embryos in the injected horn (alien + native) increased less steeply and the proportion of dead and resorbing embryos began to rise. 10. The 3½-day → 2½-day series gave some evidence that when the number of implantations in the injected horn was raised above the normal level, successful implantation in the uninjected horn was reduced, so that the total number in the two horns combined never exceeded an average of about 8½. 11. The experimental results are discussed in the light of previous work and of future application. We conclude that with reasonable control of natural and technical hazards a yield of about 50% of fertilized mouse eggs recovered as live young should be attainable.

/pdf/studies-on-the-transfer-of-fertilized-mouse-eggs-to-uterine-1561r8vprn.pdf

Studies on the Transfer of Fertilized Mouse Eggs to Uterine Foster-Mothers: I. Factors Affecting the Implantation and Survival of Native and Transferred Eggs

The distribution of XX and XY cells in XX ⇆ XY chimaeric mouse testes was analysed by enzyme marker analysis of separated testicular tissues and by in situ DNA marker analysis of air-dried testicular cells and testis sections. XX cells contributed to the Leydig cells, the peritubular cells and the vascularized connective tissue of the tunica albuginea. The Sertoli cells, on the other hand, appeared to be exclusively XY. These results indicate that during the development of the testis, Sertoli cell differentiation is triggered by cell-autonomous activity of the Y chromosomal testis-determining gene Tdy. Subsequent steps in testis differentiation may be a consequence of Sertoli cell activity.

/pdf/cell-autonomous-action-of-the-testis-determining-gene-2cc8qrrvhl.pdf

Cell-autonomous action of the testis-determining gene: Sertoli cells are exclusively XY in XX—XY chimaeric mouse testes

When pre-implantation embryos were transferred to the oviducts of pseudopregnant recipient females, on the 1st day post coitum, the percentage of females becoming pregnant was greater when a very small inoculum volume was used. The number of eggs injected per oviduct, in the range from two to ten, did not significantly affect the percentage developing into foetuses. The pregnancy rate was lower for one\\x=req-\\ cell than for two-cell and eight-cell eggs, morulae and blastocysts, but the percentage of eggs developing into live foetuses in those females which became pregnant was similar for all stages. Blastocysts transferred to the oviducts of recipients on the first day p.c. passed down the oviduct at a rate similar to that of the recipients' own unfertilized eggs. Removal of the zona pellucida with pronase prevented almost entirely the development of eight-cell eggs to foetuses after transfer to oviducts of recipients on the 1st day p.c., although development in vitro was not affected. Removal of the zona did not reduce the proportion of blastocysts developing successfully, after transfer to either oviduct or uterus. It was concluded that the zona pellucida is necessary for the transit of cleavage stages through the oviduct in normal pregnancy. The rate of transmigration between uterine horns following transfer to the oviduct was very low (0\\m=.\\4%).

/pdf/transfer-to-the-mouse-oviduct-of-eggs-with-and-without-the-azmd94r8cu.pdf

Transfer to the mouse oviduct of eggs with and without the zona pellucida.

Half embryos produced from 8-cell or compacted stages were cultured in vitro for 1-2 days and transferred to oviducts or uteri of recipients at different stages of pseudopregnancy. The proportion of live fetuses was low (8-12%), except for one group (27%) in which half embryos were cultured in vitro for 1 day and transferred into oviducts on the 1st day of pregnancy. Monozygotic twin production rate, however, was low (1 out of 10) even in this group. Fetal weight on the 18th day of gestation was significantly lower after transfer of half embryos than after transfer of similarly treated but undivided embryos. Half embryos produced from the 2-cell stage were inserted into empty zonae, embedded in agar, cultured in ligated mouse oviducts for 2-4 days and transferred to oviducts of recipient females on the 1st day of pregnancy or pseudopregnancy. When twin embryos cultured for 2-3 days were transferred to pseudopregnant recipients together with control embryos, 4 sets of monozygotic twins and 5 singletons out of 10 sets of twin embryos were obtained on Days 18-19 of gestation, giving a survival rate of 65%.

/pdf/effect-of-various-procedures-on-the-viability-of-mouse-3pfjxbroi2.pdf

Anne McLaren

Papers

Sexually dimorphic development of mouse primordial germ cells: switching from oogenesis to spermatogenesis.

Studies on the Transfer of Fertilized Mouse Eggs to Uterine Foster-Mothers: I. Factors Affecting the Implantation and Survival of Native and Transferred Eggs

Cell-autonomous action of the testis-determining gene: Sertoli cells are exclusively XY in XX—XY chimaeric mouse testes

Transfer to the mouse oviduct of eggs with and without the zona pellucida.

Effect of various procedures on the viability of mouse embryos containing half the normal number of blastomeres.