Estrogen and progesterone receptors and antioxidant enzymes are expressed differently in the uterus of domestic cats during the estrous cycle

The domestic cat, similar to the mare, ewe and goat, is a photopositive seasonal polyestric species, so that its estrous cycle is influenced by luminosity and there are multiple cycles within a season followed by a period of non-cyclicity (anestrus) [1,2]. However, unlike these species, the cat is a domestic animal species that has induced ovulation, so that the cat estrous cycle includes proestrus, estrus, interestrus and, if ovulation occurs, diestrus [1,3]. However, the molecular mechanisms involved in the control of the cat reproductive function are still poorly known [4,5].

It is known that different factors modulate the function of the female reproductive tract, including sex hormones and antioxidant enzymes [[6], [7], [8]], and alterations in the signaling or expression of these mediators in women and animals are associated with reproductive dysfunction and gestational diseases such as infertility, anovulation, premature birth, and spontaneous abortion [[8], [9], [10], [11], [12], [13]].

Studies on the expression of the progesterone (P4) receptor (PR) in the genital tract of women and female dogs have demonstrated its relationship with the development of breast, ovarian, and uterine cancer [14,15], while infertility and subfertility were demonstrated in knockout mice for estrogen receptors alpha (ERα) and beta (ERβ), respectively [9,16]. Androgen receptor total knockout mice (ArKO) show greater follicular atresia and reduced folliculogenesis [17], while the gene deletion of androgen receptors (AR) in granulosa cells (GrC-ArKO) of female mice caused subfertility and reduced folliculogenesis and birth rate [17,18].

Studies in female mice have also demonstrated that sex hormones act in the uterus by regulating antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX), and the enzymatic profile is variable according to the phase of the estrous cycle [19]. This suggests that changes in the expression of these mediators may be involved in preparing the uterus for the gestation process. The oxidative and antioxidant conditions must be carefully balanced so that processes such as placental steroidogenesis, angiogenesis, embryo implantation, pregnancy, and parturition can occur properly [8,[20], [21], [22]]. Hence, it was demonstrated in the uterus of rats that the increase in estradiol (E2) and androgens increased oxidative stress and decreased the activity of antioxidant enzymes such as catalase [19]. Conversely, progesterone stimulated glutathione peroxidase activity in the uterus of rats and mice [19,23].

However, even though the domestic cat is an ovulation-induced species, which differs from other domestic animal species and women [24], studies on the expression profile of receptors for sex steroids and antioxidant enzymes in the female genital system of this animal species are scarce. The only study carried out by Li et al. [25] and Weiguo et [25]. showed that the expression of ERα and PR in the uterus of female cats varies according to the phase of the estrous cycle, with higher expression in proestrus, being that estradiol and progesterone are the primary regulators of ER and PR expression in uterus of the cat, while Amelkina et al. [26] showed that the gene expression of these receptors and AR varies according to the stage of luteal development. Thus far, there is no description of the profile of antioxidant enzymes in the uterus of the domestic cat and whether there is a correlation between their expression with the plasma profile of sex hormones and the tissue expression of their receptors. Therefore, the present study evaluated the expression profile of sex steroid receptors and antioxidant enzymes in the uterus of domestic cats during the estrous cycle.

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