Endocrine and Reproductive Repercussions of Immunization Against Progesterone and Oestradiol in Female Rats

Abstract

Mature female rats were immunized with BSA-conjugates of oestradiol17\g=b\-6-carboxymethyloxime or progesterone-11-hemisuccinate. Sera tested two months later at 1/2000 dilution bound 63.3 % \ m=+-\3.1 sem and 21.2% \ m=+-\ 2.3 of the homologous tritiated hormone (10 pg), -oestradiol-17\g=b\(Oe2) and progesterone (P), respectively. Rats immunized against Oe2 had a significantly longer oestrous cycle (8.2 days vs. 4.5 days in BSA-immunized rats), with a prolonged leukocytic phase. The cycle of rats immunized against P was also prolonged (10.5 days), but in this group the cornified smear phase was abnormally extended. The luteinizing hormone (LH) normally observed on the afternoon of pro-oestrus failed to occur in the rats immunized against Oe2 and in 70 % of rats immunized against P. The latter animals, however, showed sporadic LH discharges during periods of persistent cornification. Immunization against P resulted in elevated total (free plus bound) plasma P levels; immunization against Oe2 prevented the pro-oestrous rise in plasma P. Mating of rats immunized against Oe2 resulted in normal pregnancies, while none of the rats immunized against P delivered.Steroid-protein conjugates have been extensively used to generate antisera for use in radioimmunoassay procedures. Less attention has been paid to the effect of such immunization on the endocrine balance and reproductive behaviour of the immunized animal.It is believed that the pre-ovulatory surge of LH, which occurs in the rat on the afternoon of pro-oestrus, depends on oestrogen secretion (Schwartz 8c

Antibodies against steroids

“…Both these effects are modified by genotype. These data support the results of earlier experiments (Raziano et al, 1972;Csapo et al, 1975;French, 1977;Kaushansky et al, 1977;Elsaesser, 1980;Rider etal, 1986Rider etal, , 1987.…”

“…Although immunization against oestrogens has infertility effects by blocking or delaying ovulation in most animals of a variety of species, there are reports demonstrating that in some immunized animals the ovulation rate and the litter size are normal or increased due, in part, to higher twining rate (Csapo et al, 1975;Kaushansky et al, 1977;Smith et al, 1981;Land et al, 1982;Sreenan, 1984). Even animals of the same species may respond differently to treatment with antibody against oestrogen (Martin et al, 1978;Wise and Schanbacher, 1983).…”

Reproductive effects of immunizing heifers against androstenedione and oestradiol-17

“…Contrary to the increased ovulation rate noted in sheep immunized against oestrogens (Smith et ai, 1981) and the anovulatory response noted by Martin et ai (1978) (Ferin et ai, 1974;Hillier, Groom, Boyns & Cameron, 1975) and animals immunized against oestradiol can still maintain pregnancy (Ferin, Raziano, Tempone & Vande Wiele, 1970 ;Csapo, Dray & Erdos, 1975 ;Kaushansky, Bauminger, Koch & Linder, 1977;Nieschlag & Wickings, 1978). Oestrogens have been reported to be higher in animals with higher titres in that they may be unavailable for clearance (Sundaram et ai, 1973) or ovarian output of oestrogens is increased because of decreased feedback effects on gonadotrophins (Pantera/., 1978;Rawlings et ai, 1978;Martensz et ai, 1979;Scaramuzzi, Martensz & Van Look, 1980b …”

Pregnancy-blocking progesterone antibody targets specifically the uterus through its progesterone-binding sites

“…As a result, progesterone antibodies can interfere with pregnancy. Active immunization with progester¬ one-bovine serum albumin (BSA) conjugate in¬ duces high levels of progesterone antibodies in the circulation and blocks pregnancy in rats (Kaushansky, Bauminger, Kock & Linder, 1977) and rabbits (Elsaesser, 1980). A series of studies with a mouse IgGl monoclonal antibody (DB3) against progester¬ one has shown that passive immunization shortly after mating prevents the onset of implantation in mice (Wright, Feinstein, Heap et al 1982), rats (Phillips, Hahn, McGuire et al 1988) and ferrets .…”