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Sterilization of female rats by single-injection of estrogen: proof-of-concept for a nonsurgical alternative

ABSTRACT: Sterilization of female rats by single-injection of estrogen: proof-of-concept for a nonsurgical alternative

PROVIDER: PRJNA912242 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR22743079_1.fastq.gz	Fastqsanger.gz
	SRR22743079_2.fastq.gz	Fastqsanger.gz
	SRR22743080_1.fastq.gz	Fastqsanger.gz
	SRR22743080_2.fastq.gz	Fastqsanger.gz

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Sterilization of female rats by single-injection of estrogen: proof-of-concept for a nonsurgical alternative

Project description:Reproductive sterilization via surgical gonadectomy is strongly advocated to help manage animal populations, especially domesticated pets, and to prevent reproductive diseases. The present study explored the feasibility of using a single-injection method for inducing sterility in female animals as an alternative to surgical sterilization. The idea was based upon our recent finding that repetitive daily injection of estrogen into neonatal rats disrupted hypothalamic expression of Kisspeptin, the neuropeptide that triggers and regulates pulsatile secretion of GnRH in the hypothalamus. In this study, neonatal female rats were dosed with estradiol benzoate (EB) by daily injection for 11 days or subcutaneously implanted with an EB-containing Silastic capsule designed to release EB over a 2- to 3-week period. Rats treated by either method did not exhibit estrous cyclicity, were anovulatory, and became infertile. The EB-treated rats had fewer Kisspeptin neurons in their hypothalami, but their GnRH-LH axis retained responsiveness to Kisspeptin stimulation. To simplify usage, an injectable EB carrier was developed in the forms of biodegradable microspheres or pellets with pharmacokinetics comparable to the EB-containing Silastic capsule. A single injection of EB microspheres (300 µg EB) to neonatal rats made them sterile and female beagles implanted with an EB pellet at a neonatal age had lower KISS expression in their hypothalami. No concerning health impact other than infertility was observed in animals that received EB treatment at a neonatal age. Taken together, this study shows that neonatal EB administration could be developed as a non-surgical animal sterilization method.

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Project description:In this proof-of-concept study, spatial transcriptomics combined with public single-cell RNA sequencing data were used to explore the potential of this technology to study kidney allograft rejection. We aimed to map gene expression patterns within diverse pathological states by examining biopsies classified across non-rejection, T cell-mediated acute rejection, and interstitial fibrosis and tubular atrophy (IFTA). Our results revealed distinct immune cell signatures, including those of T and B lymphocytes, monocytes, mast cells, and plasma cells, and their spatial organization within the renal interstitium. We also mapped chemokine receptors and ligands to study immune-cell migration and recruitment. Finally, our analysis demonstrated differential spatial enrichment of transcription signatures associated with kidney allograft rejection across various biopsy regions. Interstitium regions displayed higher enrichment scores for rejection-associated gene expression patterns than did tubular areas, which had negative scores. This implies that these signatures are primarily driven by processes unfolding in the renal interstitium. Overall, this study highlights the value of spatial transcriptomics for revealing cellular heterogeneity and immune signatures in renal transplant biopsies, and demonstrates its potential for studying the molecular and cellular mechanisms associated with rejection. However, certain limitations must be borne in mind regarding the development and future applications of this technology.

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Project description:Estrogen induce organ-specific cell proliferation and development in female reproductive organs, though the reproductive differentiation, sex maturation, implantation and lactation. However, the mechanism of organ-specific estrogen responsive genes is unknown. Thus, we examined early estrogen responsive genes in mouse uterus, vagina and mammary gland. Keywords: organ specificity 70-day-old ovariectomized mice (C57BL/6J)(n=4) were treated with 17beta-estradiol (5micro g/kg) or sesame oil. Whole uterus (Ut), vagina (Vg) and mammary gland (Mg) were sacrificed 6h after the injection.

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