Hydroxysteroid (17-beta) dehydrogenases (HSD17Bs) have a significant role in steroid metabolism by catalysing the conversion between 17-keto and 17b-hydroxysteroids. However, several studies in vitro have shown that some of these enzymes may also be involved in other metabolic pathways. Among these enzymes, HSD17B12 has been shown to be involved both in the biosynthesis of estradiol and in the fatty acids synthesis in vitro. We have earlier shown that mice with a null mutation of the Hsd17b12 gene are embryonic lethal. The aim of the present study was to investigate the role of HSD17B12 enzyme in the female mouse fertility by using mice having only one functional allele of Hsd17b12 gene (HSD17B12HE mice). Our preliminary data show that HSD17B12HE female mice are subfertile. As compared with wild type (WT), HSD17B12HE mice have significantly smaller litter sizes and longer periods between parturitions. In line with this, the length of the estrous cycle, specifically the diestrus phase, is prolonged. Histological analysis further revealed double-oocyte follicles in the HSD17B12HE mouse ovaries. In addition, trapped oocytes were seen in the corpus luteum indicating that follicles do not rupture properly during the ovulation. According to previous studies, prostaglandins (PGs), especially PGE2 are needed for follicular rupture during the ovulation in mouse. We have previously shown that the amount of arachidonic acid, a substrate for prostaglandin synthetase (COX-2), is significantly decreased in the tissues of HSD17BHE mice. We, thus, hypothesize that HSD17B12 and consequently arachidonic acid as a substrate for COX-2 is needed for normal oocyte development, ovulation and fertility in mouse