Developmental and Reproductive Toxicity Evaluation
Preclinical evaluation for innovative drugs plays an essential role in predicting potential drug toxicity before they are first applied to humans. Our company provides leading-edge drug developmental and reproductive toxicity evaluation services and essential platforms to help you get ahead of the curve in the therapeutics development for autoimmune diseases & inflammation.
Reproductive toxicology focuses on the damaging effects of drugs on the reproductive system and their impact on the offspring, including the processes of germ cell genesis and maturation, fertilization of the oocyte, and development and implantation of the fertilized egg. Developmental toxicology, on the other hand, focuses on the effects of drugs on the embryonic development of the newborn child after maternal drug administration.
Reproductive Toxicity of Drugs
Reproductive toxicity of drugs includes impairment of reproductive function and harmful effects on the offspring. Reproductive toxicity can occur during pregnancy, as well as during pre-pregnancy or breastfeeding, and is manifested by drug damage to the entire reproductive process, including germ cell genesis, fertilization of the oocyte, embryo formation and development, delivery and breastfeeding.
Reproductive Toxicity to Females
Reproductive toxicity to females is mainly seen in their effects on the processes of oogenesis, ovulation and fertilized egg implantation.
Fig.1 Hypothalamic-pituitary-gonadal (HPG) axis
(Chung D.D., et al., 2021)
- Effects on Follicles and Eggs
Follicle development goes through four stages: primordial follicle, primary follicle, secondary follicle and mature follicle. During follicular development, the three periods of mitosis of the oogonia and granulosa cells, meiosis of the oogonia to form the oocyte, and differentiation of the granulosa cells and membrane cells are the most sensitive to drugs. - Effects on Ovarian Somatic Cells and Reproductive Tracts
Some drugs may affect the developmental integrity of mature follicles or the transport of fertilized eggs for implantation. For example, nitrofurantoin may be associated with ovarian atrophy, and the heavy metal cadmium may cause atrophy of the fallopian tubes and uterus, further affecting implantation of the fertilized egg. - Effects on Hormonal Regulation of Reproductive Function
The endocrine regulation of female reproductive function is complex, with the release of GnRH from the hypothalamic-pituitary-gonadal axis and the two major gonadotropins LH and FSH regulating the ovarian cycle, and is closely related to the feedback mechanisms of estrogen and progesterone.
Reproductive Toxicity to Males
The toxicity of drugs to the male reproductive system can be seen in their effects on germ cell genesis and maturation, as well as indirect damage to the nervous and endocrine systems that regulate reproductive function.
Fig.2 Consequences of Prenatal Alcohol Exposure
(Chung D.D., et al., 2021)
- Effects on Spermatogenesis
Some drugs are particularly prone to damage DNA or affect cell protein function or cellular respiration needed for fast-growing tissues, which can impair spermatogenesis by causing damage to the processes of genetic material replication and cell division during spermatogenesis. - Impairment of Endocrine System
Impairment of male reproductive system function can also be secondary to endocrine system toxicity reactions. The reproductive toxicity of drugs in males may involve complex regulatory mechanisms in the central nervous system and the endocrine system, and thus any impairment of this regulatory system can lead to reproductive toxicity.
Our Services
With the development of molecular biology technology and its wide application in the medical field, it provides more and more choices and possibilities for the development of novel therapies for autoimmune diseases. Our company provides drug safety evaluation services with the support from multidisciplinary experts and utilization of various technological platforms.
The purpose of developmental and reproductive toxicity trials is to reveal the effects of drugs relevant to human risk assessment on mammalian reproduction. The following stages of reproduction are generally assessed:
Stage A
From pre-mating to conception
Adult male and female reproductive function, gamete development and maturation, mating behavior, fertilization
Stage B
From conception to implantation
Adult female reproductive function, preimplantation development, implantation
Stage C
From implantation to hard palate closure
Adult female reproductive function, embryonic development, major organ formation
Stage D
From hard palate closure to end of pregnancy
Adult female reproductive function, litter development and growth, organ development and growth
Stage E
From birth to weaning
Labor and lactation, adaptation of newborn pups to life outside the uterus, pre- weaning development and growth
Stage F
From weaning to sexual maturity
Post- weaning development and growth, adaptation to independent living, onset of puberty and attainment of full sexual function, effects on the second generation
For each drug, the phase being assessed should be identified and the most appropriate test to conduct should be determined. In developing a comprehensive and integrated trial strategy to assess effects on reproduction and development, these stages are typically assessed using three in vivo tests:
- Fertility and Early Embryonic Development Tests (FEED) - Stages A and B
- Embryo-Fetal Development Tests (EFD) - Stages C and D
- Perinatal Development Tests (PPND) - Stages C to F
Our Advantages
Extensive Experience
We have extensive experience in drug safety evaluation.
Advanced Technology
We have advanced laboratory facilities and technology platforms.
Customizable Solution
We can provide customized solutions based on specific project objectives.
Competitive Price
Our prices for quality services are highly competitive.
Staffed by experts in novel drug discovery and researchers engaged in pharmacology and toxicology with a solid foundation in preclinical safety evaluation of therapeutic drugs, our company is committed to providing you with professional services in the development of therapeutic drugs for Autoimmune Diseases & Inflammation. If you are interested in our services, please don't hesitate to contact us.
Reference
- Chung, Dae D et al. "Toxic and Teratogenic Effects of Prenatal Alcohol Exposure on Fetal Development, Adolescence, and Adulthood." International journal of molecular sciences 22,16 (2021) 8785.