All‐trans retinoic acid improves goat oocyte nuclear maturation and reduces apoptotic cumulus cells during in vitro maturation

Abstract

All-trans retinoic acid (t-RA) is a natural component and representative physiologically active metabolite of vitamin A, having multiple physiologic functions. The objective of this study was to evaluate the effect of t-RA on goat oocyte maturation and cumulus cell apoptosis during in vitro maturation (IVM). Immature goat cumulus-oocyte complexes (COCs) were matured in vitro in the absence or presence of t-RA at concentrations of 10 nmol/L, 100 nmol/L and 1000 nmol/L. Oocyte maturation and embryo development were assessed by polar body formation and parthenogenetic activation, respectively. Oocyte survival was checked by Trypan blue staining. Apoptosis of cumulus cells was analyzed by terminal deoxynucleotidyl transferase nick end labeling staining and quantitative real-time PCR. In comparison with the control group, 100 nmol/L and 10 nmol/L t-RA significantly improved goat nuclear oocyte maturation and survival (P < 0.05). Addition of 1000 nmol/L t-RA improved nuclear maturation (P < 0.05), but had no effect on survival of goat oocytes. t-RA had no positive effect on goat parthenogenetic embryonic cleavage, blastocyst formation or total cell numbers. However, t-RA inhibits the apoptosis of cumulus cells (P < 0.01). t-RA treatment up-regulated the expression of B-cell lymphoma 2 (BCL-2), catalase (CAT) (P < 0.05) and down-regulated the expression of Caspase-8 (P < 0.05). In conclusion, t-RA has positive effects on goat oocyte nuclear maturation and reduces apoptotic cumulus cells during IVM.

Retinoic Acid and Germ Cell Development in the Ovary and Testis

“…Recent in vitro studies have proposed that both all-trans and 9-cis RA can act on granulosa cells to improve oocyte maturation in several mammals, including cows [89][90][91][92][93], goats [94], pigs [95], rats [96], and mice [97,98] (reviewed in [99,100]). RARs and RXRs are expressed in granulosa cells surrounding full-grown oocytes [96,101,102].…”

“…RARs and RXRs are expressed in granulosa cells surrounding full-grown oocytes [96,101,102]. Supplementation of culture medium with all-trans or 9-cis RA induces granulosa cells to express genes that regulate differentiation and prevent apoptosis [90,[92][93][94]103,104] (reviewed in [99]), suggesting that RA acts on granulosa cells to prevent their aberrant differentiation state and apoptosis. In vivo, RARE-lacZ signal is detected in granulosa cells of mouse ovarian follicles at 3 weeks of age, and increased after injection of a gonadotropic hormone [102], supporting a role for RA on these cells.…”

Effects of all<i>-trans</i> retinoic acid on the <i>in vitro</i> maturation of camel (<i>Camelus dromedarius</i>) cumulus-oocyte complexes

“…Retinoic acid (RA) is a metabolite of vitamin A (retinol) that mediates the functions of vitamin A, such as cell growth, development, and differentiation, and has been implicated in reproductive processes including folliculogenesis and embryonic survival [8]. In the last two decades, several reports have revealed the crucial role of the two major retinol metabolites, all- trans and 9- cis retinoic acid, on oocyte maturation and its developmental competence in different mammalian species, both in vivo and in vitro [9,10,11,12,13,14,15,16,17,18,19,20,21]. However, to the best of our knowledge, there are no reports regarding the effects of RA on camel oocytes.…”

All‐trans retinoic acid exposure increases connexin 43 expression in cumulus cells and improves embryo development in bovine oocytes

“…Another study, by Pauli et al () showed that oocytes obtained from follicles with higher ATRA concentrations yielded a higher percentage of embryos with higher quality grades. Further, goat oocytes treated with ATRA had increased nuclear maturation compared to control oocytes (Pu et al, ). While it has been shown that retinol treatment in vivo improves the blastocyst rate of recovered bovine COCs (Shaw et al, ), currently we are not aware of any studies investigating ATRA's effects on development.…”