Folliculogenic factors in photoregressed ovaries: Differences in mRNA expression in early compared to late follicle development

Abstract

The early stages of ovarian folliculogenesis generally progress independent of gonadotropins, whereas later stages require signaling initiated by FSH. In Siberian hamsters, cycles of folliculogenesis are mediated by changes in photoperiod which depress the hypothalamic pituitary gonadal axis. Reduced gonadotropins lead to decreases in mature follicle development and ovulation; however, early stages of folliculogenesis have not been explored in regressed ovaries. We hypothesized that intraovarian factors that contribute predominantly to later stages of folliculogenesis would react to changes in photoperiod, whereas factors contributing to earlier stages would not change. To probe if the early stages of folliculogenesis continue in the photoinhibited ovary while late stages decline, we measured the mRNA abundance of factors that interact with FSH signaling (Fshr, Igf1, Cox2) and factors that can function independently of FSH (c-Kit, Kitl, Foxo3, Figla, Nobox, Sohlh1, Lhx8). While plasma FSH, antral follicles, and corpora lutea numbers declined with exposure to inhibitory photoperiod, the numbers of primordial, primary, and secondary follicles did not change. Expression of factors that interact with FSH signaling changed with changes in photoperiod; however, expression of factors that do not interact with FSH were not significantly altered. These results suggest that the photoinhibited ovary is not completely quiescent, as factors important for follicle selection and early follicle growth are still expressed in regressed ovaries. Instead, the lack of gonadotropin support that characterizes the non-breeding season appears to inhibit only final stages of folliculogenesis in Siberian hamsters.

Assessing recrudescence of photoregressed Siberian hamster ovaries using in vitro whole ovary culture

“…Although Kitl mRNA was expressed in the cultured cLD and cSD ovaries in the presence or absence of GT, no significant changes in expression were noted across photoperiod or GT treatments (Figure d). These results mirror in vivo observations in Siberian hamsters where photoperiod changes have no effect on the mRNA expression of multiple early folliculogenic factors, including Kitl and its receptor cKit (Salomon et al, ). Additional studies using the whole ovarian culture of photoregressed ovaries may be able to tease apart the individual contributions of intraovarian factors and GT to the process of recrudescence.…”

“…Consistent with previous in vivo studies, ovaries from adult Siberian hamsters housed for 14 weeks in SD were photoregressed, as demonstrated by reductions in ovarian mass as compared with ovaries from hamsters housed in stimulatory LD (Salverson et al, , Shahed & Young, ). In vivo transfer of photoregressed Siberian hamsters to LD stimulation increases plasma FSH and estradiol concentrations, ovarian mass, antral follicle development, and ovulation (Salomon et al, , Salverson et al, , Shahed, McMichael et al, , Zysling et al, ), with increases in both plasma FSH concentration and fshr mRNA noted after just 4 days after transfer from SD to LD photoperiods (Shahed, McMichael et al, ). While the intraovarian mechanism of in vivo photostimulated recrudescence has not been fully elucidated, less is known about the survival or growth of cultured photoregressed ovaries.…”

“…Seasonally breeding animals reduce their reproductive function after exposure to inhibitory photoperiod regimes, whereas exposure to stimulatory photoperiod promotes recrudescence of gonadal function (Buchanan & Yellon, , Glass, ). In Siberian hamsters ( Phodopus sungorus ), exposure to less than 12 hr of light per day inhibits the hypothalamic pituitary gonadal (HPG) axis, ultimately reducing circulating follicle stimulating hormone (FSH) and luteinizing hormone (LH) concentrations (Buchanan & Yellon, , Glass, , Salomon, Leon, Campbell, & Young, , van den Hurk, Dijkstra, & De Jong, ). As a result, short photoperiod exposure induces declines in folliculogenesis, estradiol production, and ovarian mass (Moffatt‐Blue, Sury, & Young, , Salverson, McMichael, Sury, Shahed, & Young, , Schiatt, Niklowitz, Hoffmann, & Nieschlag, ).…”

“…As a result, short photoperiod exposure induces declines in folliculogenesis, estradiol production, and ovarian mass (Moffatt‐Blue, Sury, & Young, , Salverson, McMichael, Sury, Shahed, & Young, , Schiatt, Niklowitz, Hoffmann, & Nieschlag, ). These regressed ovaries are substantially different both functionally and morphologically from ovaries in reproductively active Siberian hamsters; folliculogenesis does not progress past the secondary follicle stage, no tertiary follicles or corpora lutea are present, and clusters of hypertrophied granulosa cells (hgc, aka luteinized atretic follicles), which may represent atretic secondary follicles are noted (Moffatt‐Blue et al, ; Salomon et al, ; van den Hurk et al, ; Zysling, Park, Mcmillan, & Place, ). Subsequent transfer of reproductively regressed Siberian hamsters to photoperiods longer than 12 hr of light restores the HPG axis, with increases in plasma FSH and estradiol, ovarian mass, tertiary follicle development and corpora luteal formation noted 1–8 weeks after transfer to stimulatory long photoperiod (Salomon et al, , Salverson et al, , Shahed, McMichael, & Young, ).…”

“…These regressed ovaries are substantially different both functionally and morphologically from ovaries in reproductively active Siberian hamsters; folliculogenesis does not progress past the secondary follicle stage, no tertiary follicles or corpora lutea are present, and clusters of hypertrophied granulosa cells (hgc, aka luteinized atretic follicles), which may represent atretic secondary follicles are noted (Moffatt‐Blue et al, ; Salomon et al, ; van den Hurk et al, ; Zysling, Park, Mcmillan, & Place, ). Subsequent transfer of reproductively regressed Siberian hamsters to photoperiods longer than 12 hr of light restores the HPG axis, with increases in plasma FSH and estradiol, ovarian mass, tertiary follicle development and corpora luteal formation noted 1–8 weeks after transfer to stimulatory long photoperiod (Salomon et al, , Salverson et al, , Shahed, McMichael, & Young, ). These in vivo studies suggest that FSH is a key mediator in photostimulated resumption of ovarian function; indeed, in vivo FSH injections to photoregressed Siberian hamsters induce increases in ovarian mass (Zysling et al, ), further conveying the importance of GT stimulation to ovarian recrudescence.…”