Brief introduction of drug reproductive toxicity research

- Nov 25, 2020-

Medicine is a double-edged sword. It can not only cure diseases and save people, but also produce adverse reactions that damage human health. Reproductive toxicity research is one of the important contents of drug toxicity research, which refers to the damage of drugs to reproductive function and ability and the unfavorable mailbox for offspring. For drugs to be used in humans, animal reproductive toxicity tests need to be comprehensively considered based on the intended indications and characteristics of the test substance.

Understanding the reproductive toxicity of drugs is very important for guiding the safety of clinical medication. The reproductive toxicity of drugs has two characteristics: sensitive to the toxic effects of drugs, at a certain dose, before damage to other systems occurs, a certain part of the reproductive process may have been damaged; the reproductive toxicity of drugs is not only manifested in the exposure of drugs The body itself can also affect offspring. Therefore, reproductive toxicity can occur both during pregnancy and during pregnancy and lactation. The drug reproductive toxicity test should implement GLP specifications. There are many research methods for the reproductive and developmental toxicity of drugs. Commonly used reproductive toxicity test programs include the following three parts of joint research:


(1) Section I (fertility and early embryonic development):


Also known as general reproductive toxicity test, it studies the effects of drugs on the entire reproductive process, and evaluates whether germ cells have adverse effects on conception ability, reproductive system and offspring after exposure to drugs. At least one animal is used in the selection of experimental animals, and rats are the first choice. Fertility and early embryo developmental toxicity tests are an important part of drug reproductive toxicity research, and they are also an indispensable content in the development of innovative drugs. The staff of Medicilon's reproductive toxicity research service platform is composed of a professional technical team led by senior domestic reproductive toxicity experts with 30 years of research experience; the animal laboratory was jointly established by Medicilon and MPI Research (American Toxicology Research Company) , Passed the International Laboratory Animal Assessment and Approval (AAALAC) and reached the GLP dual standards of FDA and CFDA.


(2) Section II (embryo-fetal development):


Teratogenic experiment to evaluate the possible embryo toxicity and teratogenicity of the drug. The purpose is to evaluate the harmful effects of exposure to the test substance from the blastocyst implantation to the closure of the hard palate (the organogenesis period) on pregnant females and on the development of embryo-fetal body. The consequences of embryo-fetal developmental toxicity are relatively more serious, and more attention should be paid to the results of this section of the test. If a variety of animals are used for testing, it may provide a more adequate test basis when the test results are extrapolated to humans. The test usually uses two animals, one is a rodent, and rats are recommended, and the other is a non-rodent, and rabbits are recommended.


(3) Section III (developmental toxicity test before and after birth)


Perinatal toxicity test, to evaluate the effects of drugs on the growth and development of fetuses after birth, to detect the adverse effects of drug administration on pregnant/lactating females and the development of embryos and offspring from embryo implantation to pup weaning. At least one animal is used in the selection of experimental animals, and rats are recommended.


The reproductive toxicity research of innovative drugs in my country basically adopts the conventional three-stage test design. The current reproductive toxicity test research of drugs is often divided into the above three-stage design. When adopting the segmented test design, pay attention to the animal adulthood and from conception The pups are administered at all stages of sexual maturity. The observation should continue for a complete life cycle (from the conception of one generation to the conception of the next generation). In actual operation, a single (full course) experimental design and a two-stage experimental design can be used for rodents according to the indications and the characteristics of the test substance.


In the study of drug reproductive toxicity, other test schemes can also be considered comprehensively according to the characteristics of the test substance, intended indications and clinical medication.