Nlrp5, a member of the NLR family pyrin domain-containing genes, is a key maternal-effect gene. It is crucial for normal pre-implantation and embryonic development, being part of the subcortical maternal complex (SCMC) [1,2,3,6,8]. It may be involved in processes related to oocyte maturation, fertilization, and early embryonic development, with potential links to infertility-related pathways [2,4,5,6,8]. Genetic models, such as knockout mouse models, have been valuable in studying its function.

In sows, knockdown of NLRP5 using RNA interference arrested early embryonic development, suggesting its essential role in zygotic genome activation [7]. In mice, Nlrp5 mutant oocytes showed abnormal mitochondrial localization, increased mitochondrial activity, reactive oxygen species accumulation, and ultimately mitochondrial depletion, leading to embryo arrest at the two-cell stage [9]. In humans, mutations in NLRP5 have been identified in patients with early embryonic arrest, oocyte maturation abnormality, and female infertility [2,5,8]. For instance, six novel NLRP5 variants were found in patients with arrested and severely fragmented embryos [2], and a novel homozygous frameshift variant in NLRP5 was associated with oocyte maturation abnormality [5].

In conclusion, Nlrp5 is essential for early embryogenesis, with its function manifested through mitochondrial regulation in oocytes and embryos. Research using gene-knockout models, both in mice and other species, has revealed its critical role in early embryonic development, and its mutations are associated with human infertility and early embryonic arrest. This understanding contributes to the study of reproductive diseases and may offer potential targets for diagnosis and treatment.

References:

1. Huang, Xingchen, Sun, Qinqiang, Chen, Dongrong, Zhang, Ming, Fu, Qiang. 2022. Nlrp5 and Tle6 expression patterns in buffalo oocytes and pre-implantation embryos. In Reproduction in domestic animals = Zuchthygiene, 57, 481-488. doi:10.1111/rda.14084. https://pubmed.ncbi.nlm.nih.gov/35044003/

2. Tong, Xiaomei, Jin, Jiamin, Hu, Zhanhong, Zhang, Yin-Li, Zhang, Songying. 2022. Mutations in OOEP and NLRP5 identified in infertile patients with early embryonic arrest. In Human mutation, 43, 1909-1920. doi:10.1002/humu.24448. https://pubmed.ncbi.nlm.nih.gov/35946397/

3. Unoki, Motoko, Uemura, Shuhei, Fujimoto, Akihiro, Sasaki, Hiroyuki. . The maternal protein NLRP5 stabilizes UHRF1 in the cytoplasm: implication for the pathogenesis of multilocus imprinting disturbance. In Human molecular genetics, 33, 1575-1583. doi:10.1093/hmg/ddae096. https://pubmed.ncbi.nlm.nih.gov/38868925/

4. Xue, Yamei, Cheng, Xiaohong, Xiong, Yuping, Li, Kun. 2022. Gene mutations associated with fertilization failure after in vitro fertilization/intracytoplasmic sperm injection. In Frontiers in endocrinology, 13, 1086883. doi:10.3389/fendo.2022.1086883. https://pubmed.ncbi.nlm.nih.gov/36589837/

5. Huang, Lingli, Wang, Yu, Lu, Fangting, Jin, Rentao, Tong, Xianhong. 2022. Novel mutations in NLRP5 and PATL2 cause female infertility characterized by primarily oocyte maturation abnormality and consequent early embryonic arrest. In Journal of assisted reproduction and genetics, 39, 711-718. doi:10.1007/s10815-022-02412-4. https://pubmed.ncbi.nlm.nih.gov/35091966/

6. Sang, Qing, Zhou, Zhou, Mu, Jian, Wang, Lei. 2021. Genetic factors as potential molecular markers of human oocyte and embryo quality. In Journal of assisted reproduction and genetics, 38, 993-1002. doi:10.1007/s10815-021-02196-z. https://pubmed.ncbi.nlm.nih.gov/33895934/

7. Peng, Hui, Liu, Fang, Li, Wenhao, Zhang, Wenchang. 2015. Knockdown of NLRP5 arrests early embryogenesis in sows. In Animal reproduction science, 163, 151-6. doi:10.1016/j.anireprosci.2015.11.004. https://pubmed.ncbi.nlm.nih.gov/26585895/

8. Xu, Yao, Qian, Ying, Liu, Yu, Xue, Songguo, Sun, Lihua. 2020. A novel homozygous variant in NLRP5 is associate with human early embryonic arrest in a consanguineous Chinese family. In Clinical genetics, 98, 69-73. doi:10.1111/cge.13744. https://pubmed.ncbi.nlm.nih.gov/32222962/

9. Fernandes, Roxanne, Tsuda, Chiharu, Perumalsamy, Alagammal L, Nelson, Lawrence M, Jurisicova, Andrea. 2012. NLRP5 mediates mitochondrial function in mouse oocytes and embryos. In Biology of reproduction, 86, 138, 1-10. doi:10.1095/biolreprod.111.093583. https://pubmed.ncbi.nlm.nih.gov/22357545/