Elsevier

Animal Reproduction Science

Volume 155, April 2015, Pages 89-98
Animal Reproduction Science

Influence of 4-hydroxylated polychlorinated biphenyls on the secretory function of bovine ovarian cells: Role of the steroidogenic factor-1 receptor

https://doi.org/10.1016/j.anireprosci.2015.02.005Get rights and content

Highlights

  • The effect of 4-hydroxylated PCBs on the ovarian hormones production was studied.

  • As the model, cultured bovine granulosa and luteal cells were used.

  • The possible way of 4OHPCBs action throughout SF-1 receptor was tested.

  • The adverse influence used 4OHPCBs on steroid hormones secretion from studied cells was observed.

  • It is possible that 4OHPCBs affect OT secretion by SF-1 receptor.

Abstract

The hydroxy-derivatives (OHPCBs) of polychlorinated biphenyls (PCBs) can accumulate in the tissues of the reproductive tract in animals and humans and may still have estrogen-like properties. Moreover, the “orphan” nuclear receptor Steroidogenic Factor-1 (SF-1) can be the target of PCBs.

The aim of the present study was to determine the effect 4OH4CB and 4OH3CB on the secretion of estradiol (E2), progesterone (P4), and oxytocin (OT) from granulosa cells of follicles <1 cm and >1 cm in diameter and from luteal cells collected at four stages of the estrous cycle of cows. Furthermore, the possibility that 4OHPCBs have an effect on OT synthesis and secretion via the SF receptor was studied using receptor blocker (F0160).

Used OHPCBs increased the secretion of P4 from the granulosa cells of follicles of both sizes and increased the secretion of OT from follicles with a diameter of >1 cm. These increases were inhibited by an SF-1 receptor blocker. In luteal cells, 4OH3CB increased the secretion of P4 and OT from luteal cells at all phases of the estrous cycle, while 4OH4CB increased OT secretion during the first half of the estrous cycle. Concomitant with the increase in OT secretion from the cells, an increase in the expression of OT precursor mRNA (NP-I/OT) was observed. This effect was inhibited by SF-1 receptor blocker.

These results indicate that 4OHPCBs impair the secretory function of ovarian steroidogenic cells by disrupting steroidogenesis and increasing OT secretion, and the receptor SF-1 appears to be essentially involved in these processes.

Introduction

Polychlorinated biphenyls (PCBs) are a group of organic chemicals that permanently pollute the environment. Many of these chemicals can mimic or block the effects of hormones involved in the regulation of reproduction in animals and humans; hence, they are referred to as “endocrine disruptors” (Roselli et al., 2000). Despite their high resistance to biodegradation in the environment, PCBs can be decomposed under the influence of physical factors (mainly light and temperature), via biological dechlorination processes by anaerobic or aerobic bacterial degradation (Fish and Principe, 1994), and by hydroxylation (Furukawa and Fujihara, 2008). Thus, hydroxylated PCBs derivatives, which are relatively stable compounds, may also accumulate in the environment (Berg et al., 2010, Nomiyama et al., 2010). As a result, the amount of PCBs in the environment declines, while the amount of 4OHPCBs, increases (Marek et al., 2013).

Depending on their chemical structure, PCBs biodegrade in different ways. Low chlorinated congeners (1–4 chlorine atoms per molecule), and congeners that have aromatic rings chlorinated at the meta-, or para-position (Komancová et al., 2003, Borja et al., 2006) are hydroxylated particularly easily. Hence, they are the most common 4-hydroxy derivatives of PCBs (Furukawa et al., 2004). Adding an single bondOH to the PCB molecule has a significant influence on the physicochemical properties and biological activity compared to the basal substance. The presence of hydroxyl groups enhances the solubility of these substances in water and makes them similar to estradiol (Colborn et al., 1993, Kitamura et al., 2005). Hydroxy-derivatives of PCBs enter the bodies of animals and humans as regular PCBs (Fernandez. et al., 2008). Furthermore, PCBs may undergo hydroxylation in the body and be re-accumulated in the tissues (Wu et al., 2011).

The effect of OHPCBs on the reproductive processes of animals and humans is not completely understood, although some studies have indicated that they have adverse effects similar to those of PCBs. It has been shown that OHPCBs can interact with the estrogen receptor (Takeuchi et al., 2011), interfere with the E2 metabolism (Kester et al., 2000), alter prostaglandin synthesis and secretion from the bovine oviduct epithelium (Wrobel et al., 2010), and increase the synthesis of leukemia inhibitor factor in the fallopian tubes of human and cattle (Reinhart et al., 1999). This latter effect can be evoked without mediation by estrogen receptors. However, OHPCBs do not always mimic the action of the parent compound; hence, it is difficult to predict their activity (Antunes-Fernandes et al., 2011). Some xenobiotics such as atrazine, PCBs 77 (3,3′,4,4′-tetrachlorobiphenyl), and PCB 153 (2,2′,4,4′,5,5′-hexachlorobiphenyl) may affect reproductive processes via the orphan receptor SF-1 (NR5A1) (Fan et al., 2007, Mlynarczuk et al., 2013), which is recognized as an important factor in the regulation of adrenal and ovarian steroidogenesis (Sadowsky and Crawford, 1998, Mendelson et al., 2005). This receptor affects the expression of the StAR gene (Sugawara et al., 2000) and other genes involved in steroidogenesis (Parker et al., 2002) in cattle; additionally, it increases the expression of the oxytocin precursor gene NP-I/OT (Wehrenberg et al., 1994). It should be noted that ovarian OT alters steroidogenesis such that progesterone is more favorably produced during luteinization of granulosa cells after the preovulatory LH surge (Brendtson et al., 1996, Jo and Fortune, 2002), stimulates the synthesis of progesterone (P4) in the early and middle stages of the cycle (Miyamoto and Schams, 1991), and is involved in a luteolytic process already underway (Flint and Sheldrick, 1983, Kotwica et al., 1997).

Therefore, the purpose of this study was to verify hypothesis that the PCB 4-hydroxy derivatives 2,4′,6′-trichlorobiphenyl-4-ol (4OH3CB) and 2,2′,4′,6′-tetrachlorobiphenyl-4-ol (4OH4CB) (Kunisue and Tanabe, 2009), can affect ovarian steroidogenesis and stimulate the SF-1 receptor, thereby affecting the synthesis and secretion of OT in ovarian steroidogenic cells.

Section snippets

Collection of ovaries

Ovaries from cows and mature heifers were collected from a local slaughterhouse 15–20 min after the animals were killed and transported to the laboratory within 1 h in an ice bath containing 0.9% NaCl supplemented with penicillin (10 IU/ml), streptomycin (100 μg/ml), amphotericin (2 μg/ml), and l-glutamine (100 μg/ml). The stage of the estrous cycle (days 2–5, 6–10, 11–15, and 16–19) was assessed using the morphological observations described by Ireland et al. (1980) and Fields and Fields (1996).

Results

None of the xenobiotics used in this work affected E2 secretion from granulosa cells (P > 0.05) (Fig. 2). Both xenobiotics increased P4 secretion (P < 0.05) from the cells of follicles <1 cm in diameter, while only 4OH3CB increased P4 secretion from the cells of follicles >1 cm (P < 0.05) in diameter, and this effect was inhibited (P < 0.05) by F-0160 (Fig. 3). In contrast, secretion of OT from the granulosa cells of follicles >1 cm in diameter was stimulated by 4OH4CB (P < 0.05), and this process was also

Discussion

The viability of both granulosa and luteal cells was not affected by the studied factors; hence, we assume that the observed changes in the function of these cells were not evoked by cytotoxic effects of the applied compounds. It is assumed that 4OHPCBs retain a substantial portion of the properties of the basic molecules; however, the detailed mechanism underlying their effect on cells is not known. The presence of the hydroxyl group increases the similarity of OHPCBs to the estradiol molecule

Conflict of interest statement

The authors declare that there are no conflicts of interest.

Acknowledgments

We thank Professors G. Kotwica and S. Okrasa (University of Warmia and Mazury, Olsztyn, Poland) and Professor G.L. Williams (Texas A&M University, Beeville, TX, USA) for providing the oxytocin, progesterone, and estradiol antisera, respectively. LH (AFP 4261-A) and FSH (APF 5679C) were purchased from Dr. A.F. Parlow (Pituitary Hormones & Antisera Center, Torrance, CA, USA). The study was supported by a grant (N/N308 006136) from the National Science Centre and by the Polish Academy of Sciences.

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