Abstract
The transcription factor p63, one of the p53 family members, plays an essential role in regulating maternal reproduction and genomic integrity as well as epidermal development. TP63 (human)/Trp63 (mouse) produces multiple isoforms: TAp63 and ΔNp63, which possess a different N-terminus depending on two different promoters, and p63a, p63b, p63g, p63δ, and p63ε as products of alternative splicing at the C-terminus. TAp63 expression turns on in the nuclei of primordial germ cells in females and is maintained mainly in the oocyte nuclei of immature follicles. It has been established that TAp63 is the genomic guardian in oocytes of the female ovaries and plays a central role in determining the oocyte fate upon oocyte damage. Lately, there is increasing evidence that TP63 mutations are connected with female infertility, including isolated premature ovarian insufficiency (POI) and syndromic POI. Here, we review the biological functions of p63 in females and discuss the consequences of p63 mutations, which result in infertility in human patients.
Highlights
The p53 family proteins play essential roles in maintaining maternal reproduction and genomic integrity, and these essential roles appear to be conserved across different organisms from invertebrates to mammals
The transcriptional p53 family members consist of p53, p63, and p73, which have a common structural backbone composed of transactivation (TA), DNA-binding domain (DBD) and oligomerization domain (OD) with differences at the C-terminal region
The current clinical literature reporting TP63-related ovarian insufficiency is diverse in patient presentations and includes isolated premature ovarian insufficiency (POI) and syndromic POI with Rapp Hodgkin syndrome (RHS), Limb-mammary syndrome (LMS), and AEC
Summary
The p53 family proteins play essential roles in maintaining maternal reproduction and genomic integrity, and these essential roles appear to be conserved across different organisms from invertebrates to mammals. While the separation between p63 and p73 is observed in vertebrates, these proteins retain highly conserved female germline-protecting roles with distinct mechanisms in oocytes [3]. TAp63 is highly expressed in the oocytes of primordial follicles, which represent the ovarian reserve and support female fertility with little to no significant expression in preovulatory follicles [4]. Aging-related maternal infertility has been associated with defects in chromosome alignment and embryonic development [7]. These observations suggest a possible implication of TAp73/∆Np73 in aging-related infertility in women. A diminished ovarian reserve (DOR) in women indicates a loss of their reproductive potential and is one of the leading causes of infertility [8]. This review will focus on the biological roles of TAp63 in oocytes and its association with fertility
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